Pubmed Chromosome Start_position End_position Enhancer_related_genes Description Species Tissue_class Experiment_class Title SNP_related SNP_id Disease Cell_class Enhancer_id Enhancer_experiment Enhancer_tar_ex_De Enhancer_type target_gene_strong_experiment target_gene_weak_experiment target_gene_other_name Enhancer_function Enhancer_function_experiment En_function_ex_de TF_other_name Experiment SNP_position SNP_experiment Target_gene TF_name target_gene_experiment_description TF_experiment_de 29364907 chr2 28389994 28391994 FOSL2 FOSL2 levels were only minimally reduced, indicating that 20861 cell proliferation is completely dependent on expression of the E6 and E7 oncogenes. human Cervix High+Lowthroughput HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression 否 HPV positive tumors cervical-derived cell line 20861 E_01_0001 Southern blot,ChIP-seq,Immunofluorescence,ChIP-qPCR,RNA-seq,FISH FOSL2 levels were only minimally reduced, indicating that 20861 cell proliferation is completely dependent on expression of the E6 and E7 oncogenes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FOSL2 levels were only minimally reduced, indicating that 20861 cell proliferation is completely dependent on expression of the E6 and E7 oncogenes. Immunohistochemical staining FOSL2 levels were only minimally reduced, indicating that 20861 cell proliferation is completely dependent on expression of the E6 and E7 oncogenes. Southern blot,ChIP-seq,Immunofluorescence,ChIP-qPCR,RNA-seq,FISH FOSL2 FOSL2 levels were only minimally reduced, indicating that 20861 cell proliferation is completely dependent on expression of the E6 and E7 oncogenes. 29363938 chr2 207527779 207529779 CREB1 The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5, CREB1, and XBP-1S mRNA increased protein synthesis by 1.80, 1.99, 1.95 and 2.20-fold respectively. human Cervix High+Lowthroughput Universal mRNA Translation Enhancement with Gold Nanoparticles Conjugated to Oligonucleotides with a Poly(T) Sequence 否 cervical cancer HeLa cell E_01_0002 Western blot,RT-PCR,PCR The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5, CREB1, and XBP-1S mRNA increased protein synthesis by 1.80, 1.99, 1.95 and 2.20-fold respectively. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5, CREB1, and XBP-1S mRNA increased protein synthesis by 1.80, 1.99, 1.95 and 2.20-fold respectively. Immunohistochemical staining The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5, CREB1, and XBP-1S mRNA increased protein synthesis by 1.80, 1.99, 1.95 and 2.20-fold respectively. Western blot,RT-PCR,PCR CREB1 The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5, CREB1, and XBP-1S mRNA increased protein synthesis by 1.80, 1.99, 1.95 and 2.20-fold respectively. 29357419 chr7 148804764 148806764 EZH2 Polycomb group proteins,EZH2, and menin binds at PAX2 gene and has been demonstrated to decrease transcription of PAX2 human Kidney High+Lowthroughput Modulation of apolipoprotein L1-microRNA-193a axis prevents podocyte dedifferentiation in high-glucose milieu 否 kidney disease epithelial cell E_01_0003 Western blot,Immunofluorescence,Transfection Polycomb group proteins,EZH2, and menin binds at PAX2 gene and has been demonstrated to decrease transcription of PAX2 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Polycomb group proteins,EZH2, and menin binds at PAX2 gene and has been demonstrated to decrease transcription of PAX2 Immunohistochemical staining Polycomb group proteins,EZH2, and menin binds at PAX2 gene and has been demonstrated to decrease transcription of PAX2 Western blot,Immunofluorescence,Transfection EZH2 Polycomb group proteins,EZH2, and menin binds at PAX2 gene and has been demonstrated to decrease transcription of PAX2 29344674 chr7 148805135 148807135 EZH2 In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR-138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. human Oral cavity High+Lowthroughput Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a ceRNA of miR?138 and releasing EZH2 in oral squamous cell carcinoma 否 oral squamous cell carcinoma oral squamous cell carcinoma cell E_01_0004 RT-qPCR,transfection,Western blot In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR-138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR-138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. Immunohistochemical staining In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR-138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. RT-qPCR,transfection,Western blot EZH2 In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR‑138; the inhibition of miR-138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. 29344090 chr12 102954386 102956386 ASCL1 As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry. human Bone marrow and lymphatic High+Lowthroughput Overexpression of the proneural transcription factor ASCL1 in chronic lymphocytic leukemia with a t(12;14)(q23.2;q32.3) 否 chronic lymphocytic leukemia chronic lymphocytic leukemia cell E_01_0005 qPCR,FISH As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry. Immunohistochemical staining As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry. qPCR,FISH ASCL1 As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry. 29344006 chr6 113930322 113932322 HDAC2 HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. human Connective High+Lowthroughput Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression 否 Sepsis macrophage E_01_0006 ChIP,qRT-PCR,Western blot HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. Immunohistochemical staining HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. ChIP,qRT-PCR,Western blot HDAC2 TNF HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. Results revealed that PAI-1, TNF, and MIP-2 expression were inhibited by theophylline, an HDAC2 enhancer, in a RAW macrophage cell line, following LPS-induced inflammation. 29342503 chr5 173229371 173231371 NKX2-5 NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. human Vascular High+Lowthroughput Molecular Basis for Dysregulated Activation of NKX2-5 in the Vascular Remodeling of Systemic Sclerosis 是 rs3095870 scleroderma associated pulmonary hypertensio smooth muscle cell of the pulmonary artery E_01_0007 Western blot,qPCR NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. Immunohistochemical staining NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. Western blot,qPCR NKX2-5,TEAD1 NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling.;TEAD1 is a member of TEA/ATTS domain family transcription regulators with distinct and important roles in VSMC differentiation and in cardiovascular disease 29339538 chr7 55016139 55018139 EGFR Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET. human Cervix High+Lowthroughput E6 Protein Expressed by High-Risk HPV Activates Super-Enhancers of the EGFR and c-MET Oncogenes by Destabilizing the Histone Demethylase KDM5C 否 human papillomaviruses CaSki cell(human cervical cancer cell line) E_01_0008 ChIP-seq,RNA-seq Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET. Immunohistochemical staining Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET. ChIP-seq,RNA-seq EGFR,KDM5C Whole genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super-enhancers in the proto-oncogenes EGFR and c-MET.;Restoration of KDM5C significantly suppressed the tumorigenicity of CaSki cells, an HPV16-positive cervical cancer cell line. 29339121 chr8 144288666 144290666 HSF1 HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells. human Gastric cancer High+Lowthroughput HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in gastric cancer cells 否 gastric cancer gastric cancer cell E_01_0009 ChIP,Real-time PCR,Western blot HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells. Immunohistochemical staining HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells. ChIP,Real-time PCR,Western blot MORC2 HSF1,EZH2 In view of this, we speculated that HSF1 may regulate ArgBP2 as well as associate with MORC2 HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells.;EZH2, as the core and contributing catalytic subunit of PRC2, which is composed of EED 29337370 chr16 28929378 28931378 CD19 GM12878 LCL and P3HR-1 Burkitt lymphoma cells stably expressing activating dCas9-VP64 were transduced with either control sgRNA or sgRNAs targeting the indicated genes(CD19 or CD86). human Lymphoid tissue bone marrow High+Lowthroughput Modulating Gene Expression in Epstein-Barr Virus (EBV)-Positive B Cell Lines with CRISPRa and CRISPRi 否 Epstein-Barr virus B cell E_01_0010 ChIP-seq,ChIA-PET,RT-PCR GM12878 LCL and P3HR-1 Burkitt lymphoma cells stably expressing activating dCas9-VP64 were transduced with either control sgRNA or sgRNAs targeting the indicated genes(CD19 or CD86). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GM12878 LCL and P3HR-1 Burkitt lymphoma cells stably expressing activating dCas9-VP64 were transduced with either control sgRNA or sgRNAs targeting the indicated genes(CD19 or CD86). Immunohistochemical staining GM12878 LCL and P3HR-1 Burkitt lymphoma cells stably expressing activating dCas9-VP64 were transduced with either control sgRNA or sgRNAs targeting the indicated genes(CD19 or CD86). ChIP-seq,ChIA-PET,RT-PCR CD19 CD86 GM12878 LCL and P3HR-1 Burkitt lymphoma cells stably expressing activating dCas9-VP64 were transduced with either control sgRNA or sgRNAs targeting the indicated genes(CD19 or CD86). GM12878 LCL and P3HR-1 Burkitt lymphoma cells stably expressing activating dCas9-VP64 were transduced with either control sgRNA or sgRNAs targeting the indicated genes(CD19 or CD86). 29334376 chr1 94526560 94528560 F3 We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. human Osteosarcoma High+Lowthroughput Positively selected enhancer elements endow osteosarcoma cells with metastatic competence 否 Osteosarcoma osteosarcoma cell E_01_0011 RNA-seq,ChIP–seq We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. Immunohistochemical staining We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. RNA-seq,ChIP–seq F3 We further show that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell outgrowth in the lung. 29331016 chr10 112947442 112949442 TCF7L2 The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. human Liver High+Lowthroughput A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C-FOS in hepatocytes 是 rs7903146 type 2 diabetes hepatocyte E_01_0012 qRT-PCR,ChIP,Transfection The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. Immunohistochemical staining The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. qRT-PCR,ChIP,Transfection TCF7L2 The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. 29327713 chr7 148804434 148806434 EZH2 EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. human Lymphoid High+Lowthroughput Expression of enhancer of zeste homolog 2 (EZH2) protein in histiocytic and dendritic cell neoplasms with evidence for p-ERK1/2-related, but not MYC- or p-STAT3-related cell signaling 否 histiocytic and dendritic cell neoplasms histiocytic and dendritic cell neoplasm cell E_01_0013 Immunohistochemical staining EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. Immunohistochemical staining EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. Immunohistochemical staining EZH2 EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. 29325110 chr5 56096484 56098484 ANKRD55 As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. human Lymphoid High+Lowthroughput Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients 是 rs71624119 multiple sclerosis peripheral blood mononuclear cell E_01_0014 RNA-Seq As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. Immunohistochemical staining As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. RNA-Seq ANKRD55 As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. 29323272 chr19 10958350 10960350 SMARCA4 Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. human Tumor High+Lowthroughput Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers 否 Tumor embryonic stem cell E_01_0015 Western blot,ATAC-seq,ChIP-seq,RNA-seq Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Immunohistochemical staining Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Western blot,ATAC-seq,ChIP-seq,RNA-seq SMARCA4 Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. 29316219 chr9 81580914 81582914 TLE1 These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival,chemotaxis and angiogenesis. human Brain High+Lowthroughput Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells 否 Glioblastoma glioblastoma-initiating cells E_01_0016 ChIP-Seq,RNA-Seq,RT-qPCR These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival,chemotaxis and angiogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival,chemotaxis and angiogenesis. Immunohistochemical staining These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival,chemotaxis and angiogenesis. ChIP-Seq,RNA-Seq,RT-qPCR TLE1 These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival,chemotaxis and angiogenesis. 29311615 chr12 54030827 54032827 HOXC5 Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. human Somatic High+Lowthroughput HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis 否 Tumor somatic cell E_01_0017 Luciferase reporter assay,Western blot,ChIP-Seq,qRT-PCR,3C-qPCR Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. Immunohistochemical staining Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. Luciferase reporter assay,Western blot,ChIP-Seq,qRT-PCR,3C-qPCR HOXC5 Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. 29309299 chr19 19143072 19145072 MEF2B Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. human Lymphoid High+Lowthroughput Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas 否 Lymphomas B cell E_01_0018 Immunohistochemical Staining Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Immunohistochemical staining Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Immunohistochemical Staining MEF2B Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. 29307778 chr17 43750876 43752876 SOST The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. human Bone High+Lowthroughput Computational and functional characterization of four SNPs in the SOST locus associated with osteoporosis 是 rs1230399,rs7220711,rs1107748,rs75901553 osteoporosis Germinal center B-cells E_01_0019 Luciferase reporter assay,ChIP,qPCR The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Immunohistochemical staining The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Luciferase reporter assay,ChIP,qPCR SOST CTCF The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. 29304378 chr6 151654024 151656024 ESR1 Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. human Bone High+Lowthroughput Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects 是 rs2982562 osteoporosis osteocyte E_01_0020 Knockout Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. Immunohistochemical staining Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. Knockout ESR1 Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. 29303507 chr11 68036369 68038369 TCIRG1 These findings suggest that TCIRG1 functions as a metastatic enhancer by modulating growth, death and EMT in HCC cells. human HCC High+Lowthroughput T-cell immune regulator 1 enhances metastasis in hepatocellular carcinoma 否 hepatocellular carcinoma HCC cell lines E_01_0021 Western blot,transfection These findings suggest that TCIRG1 functions as a metastatic enhancer by modulating growth, death and EMT in HCC cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings suggest that TCIRG1 functions as a metastatic enhancer by modulating growth, death and EMT in HCC cells. Immunohistochemical staining These findings suggest that TCIRG1 functions as a metastatic enhancer by modulating growth, death and EMT in HCC cells. Western blot,transfection TCIRG1 These findings suggest that TCIRG1 functions as a metastatic enhancer by modulating growth, death and EMT in HCC cells. 29300379 chr15 67061032 67063032 SMAD3 These variants regulate SMAD3 transcription in an allele-specific manner through enhancer elements in introns of SMAD3. human Thyroid High+Lowthroughput The role of SMAD3 in the genetic predisposition to papillary thyroid carcinoma 是 rs17293632,rs4562997 papillary thyroid carcinoma thyroid cancer cell lines E_01_0022 ChIP,siRNA Knockdown,Luciferase reporter assay,Transfection,qPCR These variants regulate SMAD3 transcription in an allele-specific manner through enhancer elements in introns of SMAD3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These variants regulate SMAD3 transcription in an allele-specific manner through enhancer elements in introns of SMAD3. Immunohistochemical staining These variants regulate SMAD3 transcription in an allele-specific manner through enhancer elements in introns of SMAD3. ChIP,siRNA Knockdown,Luciferase reporter assay,Transfection,qPCR SPRY4 SMAD3 The sprouty RTK signaling antagonist 4 (SPRY4)gene was found to be the second-most dysregulated candidate gene These variants regulate SMAD3 transcription in an allele-specific manner through enhancer elements in introns of SMAD3. 29300302 chrX 129537551 129539551 OCRL The OCRL1 protein contains several domains, including an N-terminal pleckstrin homology (PH) domain, a central 5-phosphatase catalytic domain, an ASH (ASPM, SPD-2, Hydin) domain,and a C-terminal noncatalytic Rho-GTPase activating protein (GAP) domain human Kidney High+Lowthroughput Splicing Analysis of Exonic OCRL Mutations Causing Lowe Syndrome or Dent-2 Disease 否 Lowe syndrome and Dent-2 disease COS7 cells E_01_0023 Transfection,RT-PCR The OCRL1 protein contains several domains, including an N-terminal pleckstrin homology (PH) domain, a central 5-phosphatase catalytic domain, an ASH (ASPM, SPD-2, Hydin) domain,and a C-terminal noncatalytic Rho-GTPase activating protein (GAP) domain Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The OCRL1 protein contains several domains, including an N-terminal pleckstrin homology (PH) domain, a central 5-phosphatase catalytic domain, an ASH (ASPM, SPD-2, Hydin) domain,and a C-terminal noncatalytic Rho-GTPase activating protein (GAP) domain Immunohistochemical staining The OCRL1 protein contains several domains, including an N-terminal pleckstrin homology (PH) domain, a central 5-phosphatase catalytic domain, an ASH (ASPM, SPD-2, Hydin) domain,and a C-terminal noncatalytic Rho-GTPase activating protein (GAP) domain Transfection,RT-PCR OCRL The OCRL1 protein contains several domains, including an N-terminal pleckstrin homology (PH) domain, a central 5-phosphatase catalytic domain, an ASH (ASPM, SPD-2, Hydin) domain,and a C-terminal noncatalytic Rho-GTPase activating protein (GAP) domain 29294297 chr7 148804388 148806388 EZH2 We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. human Dental pulp High+Lowthroughput EZH2 Impairs Human Dental Pulp Cell Mineralization via the Wnt/β-Catenin Pathway 否 Oral Diseases dental pulp cell E_01_0024 ChIP We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. Immunohistochemical staining We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. ChIP EZH2 We conclude that EZH2 plays a negative role during the odontogenic differentiation of hDPCs. 29294065 chr19 33297489 33299489 CEBPA Therefore, CEBPA is likely to bind to the “c” region of the PCP4 promoter. human Adrenal High+Lowthroughput Purkinje Cell Protein 4 Expression Is Associated With DNA Methylation Status in Aldosterone-Producing Adenoma 否 adrenocortical adenoma cortical cell of adrenal gland E_01_0025 qPCR,ChIP Therefore, CEBPA is likely to bind to the “c” region of the PCP4 promoter. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, CEBPA is likely to bind to the “c” region of the PCP4 promoter. Immunohistochemical staining Therefore, CEBPA is likely to bind to the “c” region of the PCP4 promoter. qPCR,ChIP CEBPA Therefore, CEBPA is likely to bind to the “c” region of the PCP4 promoter. 29286144 chr7 148804229 148806229 EZH2 Overall, the present study demonstrated that the lncrna PVt1 may contribute to the tumorigenesis and metastasis of melanoma through binding to eZH2 and regulating the expression of mir-200c. human Melanoma High+Lowthroughput Effect of long non-coding RNA PVT1 on cell proliferation and migration in melanoma 否 Melanoma melanoma cells E_01_0026 Western blot,ChIP Overall, the present study demonstrated that the lncrna PVt1 may contribute to the tumorigenesis and metastasis of melanoma through binding to eZH2 and regulating the expression of mir-200c. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overall, the present study demonstrated that the lncrna PVt1 may contribute to the tumorigenesis and metastasis of melanoma through binding to eZH2 and regulating the expression of mir-200c. Immunohistochemical staining Overall, the present study demonstrated that the lncrna PVt1 may contribute to the tumorigenesis and metastasis of melanoma through binding to eZH2 and regulating the expression of mir-200c. Western blot,ChIP EZH2 Overall, the present study demonstrated that the lncrna PVt1 may contribute to the tumorigenesis and metastasis of melanoma through binding to eZH2 and regulating the expression of mir-200c. 29286132 chr7 148804179 148806179 EZH2 Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC human Kidney High+Lowthroughput EZH2 enhances the invasive capability of renal cell carcinoma cells via activation of STAT3 否 renal cell carcinoma nephrocyte E_01_0027 Western blot Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC Immunohistochemical staining Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC Western blot EZH2 Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC 29259014 chr7 55016411 55018411 EGFR We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib þ THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. human Lung High+Lowthroughput "ER Stress Signaling Promotes the Survival of Cancer ""Persister Cells"" Tolerant to EGFR Tyrosine Kinase Inhibitors" 否 Tumor PC9 cells E_01_0028 qRT-PCR,RNA-seq We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib þ THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib þ THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. Immunohistochemical staining We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib þ THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. qRT-PCR,RNA-seq EGFR We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib þ THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. 29256825 chr4 108045000 108047000 LEF1 β-catenin nuclear translocation, T cell factor (TCF) and lymphoid enhancerbinding factor (LEF) up-regulation have been shown to be involved in canonical Wnt pathways [20], and in our studies, Western blot results showed that the amount of β- catenin protein in nuclei was increased in treated cells human Liver High+Lowthroughput Salvianolic Acid B Enhances Hepatic Differentiation of Human Embryonic Stem Cells Through Upregulation of WNT Pathway and Inhibition of Notch Pathway 否 Liver disease Hepatocytes E_01_0029 qRT-PCR,Immunofluorescence staining,PCR,Western blot β-catenin nuclear translocation, T cell factor (TCF) and lymphoid enhancerbinding factor (LEF) up-regulation have been shown to be involved in canonical Wnt pathways [20], and in our studies, Western blot results showed that the amount of β- catenin protein in nuclei was increased in treated cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq β-catenin nuclear translocation, T cell factor (TCF) and lymphoid enhancerbinding factor (LEF) up-regulation have been shown to be involved in canonical Wnt pathways [20], and in our studies, Western blot results showed that the amount of β- catenin protein in nuclei was increased in treated cells Immunohistochemical staining β-catenin nuclear translocation, T cell factor (TCF) and lymphoid enhancerbinding factor (LEF) up-regulation have been shown to be involved in canonical Wnt pathways [20], and in our studies, Western blot results showed that the amount of β- catenin protein in nuclei was increased in treated cells qRT-PCR,Immunofluorescence staining,PCR,Western blot LEF1 β-catenin nuclear translocation, T cell factor (TCF) and lymphoid enhancerbinding factor (LEF) up-regulation have been shown to be involved in canonical Wnt pathways [20], and in our studies, Western blot results showed that the amount of β- catenin protein in nuclei was increased in treated cells 29249800 chr18 27930050 27932050 CDH2 DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. human CRPC High+Lowthroughput DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7 否 castration-resistant prostate cancer castration-resistant prostate cancer cell E_01_0030 qRT-PCR,ChIP,3C DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. Immunohistochemical staining DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. qRT-PCR,ChIP,3C CDH2 DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. 29248547 chr7 148804663 148806663 EZH2 Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation(H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL. human PCALCL High+Lowthroughput Dual Role of EZH2 in Cutaneous Anaplastic Large Cell Lymphoma: Promoting Tumor Cell Survival and Regulating Tumor Microenvironment 否 cutaneous CD30+ lymphoproliferative disease Primary cutaneous anaplastic T cell lymphoma cell E_01_0031 ChIP,qRT-PCR,Western blot Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation(H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation(H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL. Immunohistochemical staining Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation(H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL. ChIP,qRT-PCR,Western blot EZH2 Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation(H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL. 29233846 chr6 47504530 47506530 Ezh2 Ezh2 is the catalytic subunit containing a SET domain, which harbors the active site for histone H3 trimethylation on lysine 27 (H3K27me3), although Suz12 and Eed association is needed for optimal enzymatic activity8. mouse Ovarian High+Lowthroughput VE-Cadherin-Mediated Epigenetic Regulation of Endothelial Gene Expression 否 Ovarian carcinoma endothelial cell E_01_0032 Immunofluorescence,Western blot,RNA-seq ,qRT–PCR,ChIP Ezh2 is the catalytic subunit containing a SET domain, which harbors the active site for histone H3 trimethylation on lysine 27 (H3K27me3), although Suz12 and Eed association is needed for optimal enzymatic activity8. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ezh2 is the catalytic subunit containing a SET domain, which harbors the active site for histone H3 trimethylation on lysine 27 (H3K27me3), although Suz12 and Eed association is needed for optimal enzymatic activity8. Immunohistochemical staining Ezh2 is the catalytic subunit containing a SET domain, which harbors the active site for histone H3 trimethylation on lysine 27 (H3K27me3), although Suz12 and Eed association is needed for optimal enzymatic activity8. Immunofluorescence,Western blot,RNA-seq ,qRT–PCR,ChIP Ezh2 Ezh2 is the catalytic subunit containing a SET domain, which harbors the active site for histone H3 trimethylation on lysine 27 (H3K27me3), although Suz12 and Eed association is needed for optimal enzymatic activity8. 29231261 chr7 148804801 148806801 EZH2 LncRNA AWPPH can promote cell proliferation, autophagy and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. human Bladder High+Lowthroughput LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression 否 bladder cancer human bladder epithelial cell line E_01_0033 Transfection,qRT-PCR,Western blot,ChIP LncRNA AWPPH can promote cell proliferation, autophagy and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LncRNA AWPPH can promote cell proliferation, autophagy and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. Immunohistochemical staining LncRNA AWPPH can promote cell proliferation, autophagy and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. Transfection,qRT-PCR,Western blot,ChIP EZH2 LncRNA AWPPH can promote cell proliferation, autophagy and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. 29227829 chr6 135178878 135180878 MYB HMI-LNCRNA might be a potential therapeutic target for HbF induction treatment in sickle cell disease and β-thalassemia. human Hematopoietic High+Lowthroughput A long noncoding RNA from the HBS1L-MYB intergenic region on chr6q23 regulates human fetal hemoglobin expression 是 rs66650371 sickle cell disease and β-thalassemia HUDEP-2 cell E_01_0034 RT–PCR,qPCR,Western blot HMI-LNCRNA might be a potential therapeutic target for HbF induction treatment in sickle cell disease and β-thalassemia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HMI-LNCRNA might be a potential therapeutic target for HbF induction treatment in sickle cell disease and β-thalassemia. Immunohistochemical staining HMI-LNCRNA might be a potential therapeutic target for HbF induction treatment in sickle cell disease and β-thalassemia. RT–PCR,qPCR,Western blot MYB,HBS1L HMI-LNCRNA might be a potential therapeutic target for HbF induction treatment in sickle cell disease and β-thalassemia.;HMI-LNCRNA might be a potential therapeutic target for HbF induction treatment in sickle cell disease and β-thalassemia. 29207119 chr7 148804312 148806312 EZH2 Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. human Breast High+Lowthroughput EZH2 inhibition sensitizes tamoxifen?resistant breast cancer cells through cell cycle regulation 否 breast cancer breast cancer cell E_01_0035 Transfection,RT-qPCR,Western blot Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. Immunohistochemical staining Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. Transfection,RT-qPCR,Western blot EZH2 Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive complex 2, is overexpressed in a number of different tumors including breast cancer, and serves important roles in cell cycle regulation, proliferation, apoptosis, tumorigenesis and drug resistance. 29180489 chr12 114350941 114352941 TBX5 TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells. human Lymphoid High+Lowthroughput Downregulation of NFAT3 Due to Lack of T-Box Transcription Factor TBX5 Is Crucial for Cytokine Expression in T Cells 否 T cell E_01_0036 Transfection TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells. Immunohistochemical staining TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells. Transfection TBX5 TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells. 29177481 chr7 148804952 148806952 EZH2 The fact that EZH2 catalyzes the methylation of H3K27me3, a repressive mark known to be induced at DNA damage sites,prompted us to test whether the level of H3K27me3 at damage sites is affected by CDYL1. human High+Lowthroughput CDYL1 fosters double-strand break-induced transcription silencing and promotes homology-directed repair 否 E_01_0037 Transfection,Immunofluorescence,Western blot,ChIP The fact that EZH2 catalyzes the methylation of H3K27me3, a repressive mark known to be induced at DNA damage sites,prompted us to test whether the level of H3K27me3 at damage sites is affected by CDYL1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The fact that EZH2 catalyzes the methylation of H3K27me3, a repressive mark known to be induced at DNA damage sites,prompted us to test whether the level of H3K27me3 at damage sites is affected by CDYL1. Immunohistochemical staining The fact that EZH2 catalyzes the methylation of H3K27me3, a repressive mark known to be induced at DNA damage sites,prompted us to test whether the level of H3K27me3 at damage sites is affected by CDYL1. Transfection,Immunofluorescence,Western blot,ChIP EZH2 The fact that EZH2 catalyzes the methylation of H3K27me3, a repressive mark known to be induced at DNA damage sites,prompted us to test whether the level of H3K27me3 at damage sites is affected by CDYL1. 29175454 chr10 68557509 68559509 TET1 To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. human Tumor High+Lowthroughput Selective inhibition of CTCF binding by iAs directs TET-mediated reprogramming of 5-hydroxymethylation patterns in iAs-transformed cells 否 iAs-mediated carcinogenesis transformed cell E_01_0038 qRT-PCR,ChIP To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. Immunohistochemical staining To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. qRT-PCR,ChIP TET2 TET1,CTCF To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site.;To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. 29162563 chr16 86507790 86509790 FOXF1 We uncover that FOXF1 defi nes the core-regulatory circuitry in GIST through both direct transcriptional regulation and pioneer factor function. human Gastrointestinal tract High+Lowthroughput FOXF1 Defines the Core-Regulatory Circuitry in Gastrointestinal Stromal Tumor 否 gastrointestinal stromal tumor gastrointestinal stromal tumor cell E_01_0039 siRNA Transfection,qRT-PCR,ChIP,ChIP-qPCR,ATAC-seq,ChIP-seq We uncover that FOXF1 defi nes the core-regulatory circuitry in GIST through both direct transcriptional regulation and pioneer factor function. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We uncover that FOXF1 defi nes the core-regulatory circuitry in GIST through both direct transcriptional regulation and pioneer factor function. Immunohistochemical staining We uncover that FOXF1 defi nes the core-regulatory circuitry in GIST through both direct transcriptional regulation and pioneer factor function. siRNA Transfection,qRT-PCR,ChIP,ChIP-qPCR,ATAC-seq,ChIP-seq FOXF1,ETV1,KIT We uncover that FOXF1 defi nes the core-regulatory circuitry in GIST through both direct transcriptional regulation and pioneer factor function.;Here, we uncover that in gastrointestinal stromal tumor (GIST), the forkhead family member FOXF1 directly controls the transcription of two master regulators, KIT and ETV1, both required for GIST precursor-interstitial cells of Cajal lineage specifi cation and GIST tumorigenesis;Here, we uncover that in gastrointestinal stromal tumor (GIST), the forkhead family member FOXF1 directly controls the transcription of two master regulators, KIT and ETV1, both required for GIST precursor-interstitial cells of Cajal lineage specifi cation and GIST tumorigenesis 29162511 chr1 11782707 11784707 MTHFR Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis human Thymus High+Lowthroughput The thymidylate synthase enhancer region (TSER) polymorphism increases the risk of thymic lymphoid hyperplasia in patients with Myasthenia Gravis 是 rs1801133 thymic lymphoid hyperplasia B cell E_01_0040 Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis Immunohistochemical staining Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis MTHFR,MTR,TYMS,MTRR Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis;Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis;Therefore, the lack of association that we observed between the TYMS TSER polymorphism and thymoma risk might be due to different histological, molecular and pathological pathways leading to either thymoma or follicular hyperplasia in MG patients;Little is still known about the contribution of MTHFR, MTR and MTRR polymorphisms in clinical subtypes of autoimmune diseases, except for some controversial studies suggesting a possible contribution of MTHFR polymorphisms to both risk and response to methotrexate treatment of rheumatoid arthritis 29154949 chr12 56115695 56117695 ESYT1 We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains. human Lung CF High+Lowthroughput A novel microscopy-based assay identifies extended synaptotagmin-1 (ESYT1) as a positive regulator of anoctamin 1 traffic 否 Cystic Fibrosis bronchial epithelial cell E_01_0041 siRNA transfection,Immunostaining We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains. Immunohistochemical staining We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains. siRNA transfection,Immunostaining ESYT1,COPB1 ANO1 We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains.;We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains. We demonstrate the robustness and specificity of this cell-based assay, by the identification of siRNAs acting both as ANO1 traffic enhancer and inhibitor, targeting respectively COPB1 and ESYT1 (extended synaptotagmin-1), the latter involved in coupling of the endoplasmic reticulum to the PM at specific microdomains. 29129693 chr17 76133482 76135482 FOXJ1 FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. human Bladder cancer High+Lowthroughput FOXJ1 promotes bladder cancer cell growth and regulates Warburg effect 否 bladder cancer bladder cancer cell E_01_0042 Western blot FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. Immunohistochemical staining FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. Western blot FOXJ1 FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. 29127222 chr15 99562705 99564705 MEF2A These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation. human Placental High+Lowthroughput MEF2 transcription factors in human placenta and involvement in cytotrophoblast invasion and differentiation 否 placenta-related pregnancy disorders cytotrophoblast cell lines E_01_0043 Transfection,Immunofluorescence,Western blot,ChIP,RT-PCR These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation. Immunohistochemical staining These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation. Transfection,Immunofluorescence,Western blot,ChIP,RT-PCR MEF2B,MEF2D MEF2A,MEF2C These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation.;These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation. These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation.;These findings suggest individual members of MEF2 family distinctively regulate 40 cytotrophoblast proliferation, invasion, and differentiation. 29106960 chr7 148804589 148806589 EZH2 Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. human Liver High+Lowthroughput Carnosol-mediated Sirtuin 1 activation inhibits Enhancer of Zeste Homolog 2 to attenuate liver fibrosis 否 hepatic fibrosis Myofibroblast E_01_0044 Western blot, RT-PCR,Immunofluorescence staining,Transfection Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. Immunohistochemical staining Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. Western blot, RT-PCR,Immunofluorescence staining,Transfection EZH2 Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. 29089464 chr7 148804445 148806445 EZH2 Histone methylation is a member of the histone modifications with histone methyltransferase activity, wherein SET and MYND domain containing 3 (SMYD3) and Enhancer of Zeste Homolog 2 (EZH2) are reported to be involved in the development of multiple cancers and play important roles in transcriptional regulation human Breast cancer High+Lowthroughput Correlations of EZH2 and SMYD3 gene polymorphisms with breast cancer susceptibility and prognosis 否 breast cancer breast cancer cell E_01_0045 RT-qPCR,Western blot Histone methylation is a member of the histone modifications with histone methyltransferase activity, wherein SET and MYND domain containing 3 (SMYD3) and Enhancer of Zeste Homolog 2 (EZH2) are reported to be involved in the development of multiple cancers and play important roles in transcriptional regulation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Histone methylation is a member of the histone modifications with histone methyltransferase activity, wherein SET and MYND domain containing 3 (SMYD3) and Enhancer of Zeste Homolog 2 (EZH2) are reported to be involved in the development of multiple cancers and play important roles in transcriptional regulation Immunohistochemical staining Histone methylation is a member of the histone modifications with histone methyltransferase activity, wherein SET and MYND domain containing 3 (SMYD3) and Enhancer of Zeste Homolog 2 (EZH2) are reported to be involved in the development of multiple cancers and play important roles in transcriptional regulation RT-qPCR,Western blot EZH2 Histone methylation is a member of the histone modifications with histone methyltransferase activity, wherein SET and MYND domain containing 3 (SMYD3) and Enhancer of Zeste Homolog 2 (EZH2) are reported to be involved in the development of multiple cancers and play important roles in transcriptional regulation 29070695 chr17 19492823 19494823 SLC47A1 These results suggest that the 5’ CpG island of SLC47A1 acts as an enhancer for SLC47A1, and DNA methylation in the CpG island plays an important role in inter-individual differences in hepatic MATE1 expression. human Liver High+Lowthroughput Relationship between DNA Methylation in the 5' CpG Island of the SLC47A1 (Multidrug and Toxin Extrusion Protein MATE1) Gene and Interindividual Variability in MATE1 Expression in the Human Liver 否 HepG2 cell E_01_0046 qRT-PCR These results suggest that the 5’ CpG island of SLC47A1 acts as an enhancer for SLC47A1, and DNA methylation in the CpG island plays an important role in inter-individual differences in hepatic MATE1 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that the 5’ CpG island of SLC47A1 acts as an enhancer for SLC47A1, and DNA methylation in the CpG island plays an important role in inter-individual differences in hepatic MATE1 expression. Immunohistochemical staining These results suggest that the 5’ CpG island of SLC47A1 acts as an enhancer for SLC47A1, and DNA methylation in the CpG island plays an important role in inter-individual differences in hepatic MATE1 expression. qRT-PCR SLC47A1 These results suggest that the 5’ CpG island of SLC47A1 acts as an enhancer for SLC47A1, and DNA methylation in the CpG island plays an important role in inter-individual differences in hepatic MATE1 expression. 29059175 chr16 67559364 67561364 CTCF Because CTCF is a multifunctional TF that can function as either an activator or a repressor of transcription, we first confirmed the role of CTCF in regulation of MSMP expression using siRNA. human Tumor High+Lowthroughput Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP) 否 Tumor cancer cell E_01_0047 qRT–PCR,Immunostaining,Western blot Because CTCF is a multifunctional TF that can function as either an activator or a repressor of transcription, we first confirmed the role of CTCF in regulation of MSMP expression using siRNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Because CTCF is a multifunctional TF that can function as either an activator or a repressor of transcription, we first confirmed the role of CTCF in regulation of MSMP expression using siRNA. Immunohistochemical staining Because CTCF is a multifunctional TF that can function as either an activator or a repressor of transcription, we first confirmed the role of CTCF in regulation of MSMP expression using siRNA. qRT–PCR,Immunostaining,Western blot MSMP CTCF These findings imply that MSMP inhibition combined with the use of antiangiogenesis drugs may be a new strategy to overcome resistance to antiangiogenesis therapy Because CTCF is a multifunctional TF that can function as either an activator or a repressor of transcription, we first confirmed the role of CTCF in regulation of MSMP expression using siRNA. 29053336 chr7 148804334 148806334 EZH2 These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other anti-fibrotic genes in IPF. human Lung High+Lowthroughput Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic Pulmonary Fibrosis 否 Pulmonary Fibrosis E_01_0048 ChIP These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other anti-fibrotic genes in IPF. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other anti-fibrotic genes in IPF. Immunohistochemical staining These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other anti-fibrotic genes in IPF. ChIP EZH2 These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other anti-fibrotic genes in IPF. 29044515 chr12 32787839 32789839 PKP2 Moreover, our data suggest that Plakophilin-2 may act as an antagonist of β-catenin/TCF complexes on Wnt-activated promoters. human Colon High+Lowthroughput The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts 否 colon cancer colon cancer-associated fibroblast E_01_0049 RNA-Seq,RT-qPCR,Western blot Moreover, our data suggest that Plakophilin-2 may act as an antagonist of β-catenin/TCF complexes on Wnt-activated promoters. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, our data suggest that Plakophilin-2 may act as an antagonist of β-catenin/TCF complexes on Wnt-activated promoters. Immunohistochemical staining Moreover, our data suggest that Plakophilin-2 may act as an antagonist of β-catenin/TCF complexes on Wnt-activated promoters. RNA-Seq,RT-qPCR,Western blot PKP2 Moreover, our data suggest that Plakophilin-2 may act as an antagonist of β-catenin/TCF complexes on Wnt-activated promoters. 28994199 chr1 47213269 47215269 TAL1 Here, addition of PD0325901 to the culture was associated with increased transcript levels of GATA1, LMO2, TAL1 and FOG which are known to be the key transcription factors for normal erythroid differentiation human Haematopoietic High+Lowthroughput Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex?vivo expanded haematopoietic stem cells 否 hematopoietic stem cell E_01_0050 qPCR,Immunohistochemical staining Here, addition of PD0325901 to the culture was associated with increased transcript levels of GATA1, LMO2, TAL1 and FOG which are known to be the key transcription factors for normal erythroid differentiation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, addition of PD0325901 to the culture was associated with increased transcript levels of GATA1, LMO2, TAL1 and FOG which are known to be the key transcription factors for normal erythroid differentiation Immunohistochemical staining Here, addition of PD0325901 to the culture was associated with increased transcript levels of GATA1, LMO2, TAL1 and FOG which are known to be the key transcription factors for normal erythroid differentiation qPCR,Immunohistochemical staining TAL1 Here, addition of PD0325901 to the culture was associated with increased transcript levels of GATA1, LMO2, TAL1 and FOG which are known to be the key transcription factors for normal erythroid differentiation 28974397 chr7 148804688 148806688 EZH2 A promising epigenetic target is EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the polycomb repressive complex 2 that methylates the 27th H3K27. human Soft High+Lowthroughput Comprehensive Genomic Sequencing of Urothelial Tumors Identifies Rare SMARCB1 (INI-1)-Deficient Carcinomas of the Urinary?System 否 urothelial carcinoma tumor cell E_01_0051 Immunohistochemical staining A promising epigenetic target is EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the polycomb repressive complex 2 that methylates the 27th H3K27. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A promising epigenetic target is EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the polycomb repressive complex 2 that methylates the 27th H3K27. Immunohistochemical staining A promising epigenetic target is EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the polycomb repressive complex 2 that methylates the 27th H3K27. Immunohistochemical staining SMARCB1 EZH2 Functioning as a tumor suppressor, biallelic loss of SMARCB1/INI1 through mutation or deletion results in tumor formation. A promising epigenetic target is EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the polycomb repressive complex 2 that methylates the 27th H3K27. 28971975 chr17 61449600 61451600 TBX4 Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. human High+Lowthroughput TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts 否 pathogenesis of respiratory diseases lung fibroblasts cell E_01_0052 RNA-seq,RT-PCR Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. Immunohistochemical staining Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. RNA-seq,RT-PCR TBX4 Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. 28939663 chr7 148804966 148806966 EZH2 As CCRK drives hepatocarcinogenesis through upregulation of EZH2,which can function as a transcriptional activator of NF-κB targets human Liver High+Lowthroughput Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy 否 hepatocellular carcinoma Myeloid-derived suppressor cell E_01_0053 Transfection As CCRK drives hepatocarcinogenesis through upregulation of EZH2,which can function as a transcriptional activator of NF-κB targets Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As CCRK drives hepatocarcinogenesis through upregulation of EZH2,which can function as a transcriptional activator of NF-κB targets Immunohistochemical staining As CCRK drives hepatocarcinogenesis through upregulation of EZH2,which can function as a transcriptional activator of NF-κB targets Transfection EZH2 As CCRK drives hepatocarcinogenesis through upregulation of EZH2,which can function as a transcriptional activator of NF-κB targets 28925507 chr7 148804490 148806490 EZH2 In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells. human CRC High+Lowthroughput (-)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells 否 colorectal cancer colorectal cancer (CRC) cell line E_01_0054 Western blot,Immunofluorescence In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells. Immunohistochemical staining In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells. Western blot,Immunofluorescence EZH2 In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells. 28925391 chr7 148804797 148806797 EZH2 Here, we show enhancer of zeste homolog 2(EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. human Tumor High+Lowthroughput EZH2 contributes to the response to PARP inhibitors through its PARP-mediated poly-ADP ribosylation in breast cancer 否 breast cancer breast cancer cell E_01_0055 ChIP,qPCR,RT-qPCR,Western blot Here, we show enhancer of zeste homolog 2(EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we show enhancer of zeste homolog 2(EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. Immunohistochemical staining Here, we show enhancer of zeste homolog 2(EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. ChIP,qPCR,RT-qPCR,Western blot EZH2 Here, we show enhancer of zeste homolog 2(EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. 28923345 chr10 67881952 67883952 SIRT1 Thus, SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR. human High+Lowthroughput SIRT1 is a transcriptional enhancer of the glucocorticoid receptor acting independently to its deacetylase activity 否 HeLa cell E_01_0056 Transfection,Western blot,RNA-seq,PCR,ChIP Thus, SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR. Immunohistochemical staining Thus, SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR. Transfection,Western blot,RNA-seq,PCR,ChIP SIRT1 Thus, SIRT1 is a novel transcriptional enhancer of GR-induced transcriptional activity possibly by functioning as a scaffold for the transcriptional complex formed on GR. 28922471 chr19 35742614 35744614 PSENEN The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. human High+Lowthroughput A phenotype combining hidradenitis suppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN 否 Dowling-Degos disease keratinocyte cell E_01_0057 qRT-PCR The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. Immunohistochemical staining The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. qRT-PCR PSENEN The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. 28902616 chr5 88714680 88716680 MEF2C The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). human Heart High+Lowthroughput MEF2C loss-of-function mutation associated with familial dilated cardiomyopathy 否 dilated cardiomyopathy HeLa cell E_01_0058 Transfection,dual-luciferase reporter assay The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). Immunohistochemical staining The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). Transfection,dual-luciferase reporter assay MEF2C The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). 28862715 chr7 148804307 148806307 EZH2 EZH2 positivity was significantly correlated with WHO tumor grade and worse prognosis in gliomas. human Tumor High+Lowthroughput Prognostic role of EZH2 in gliomas: a meta-analysis 否 gliomas tumor cell E_01_0059 Meta-analysis EZH2 positivity was significantly correlated with WHO tumor grade and worse prognosis in gliomas. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 positivity was significantly correlated with WHO tumor grade and worse prognosis in gliomas. Immunohistochemical staining EZH2 positivity was significantly correlated with WHO tumor grade and worse prognosis in gliomas. Meta-analysis EZH2 EZH2 positivity was significantly correlated with WHO tumor grade and worse prognosis in gliomas. 28858300 chr7 148804693 148806693 EZH2 Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. human Tumor High+Lowthroughput Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors 否 Tumor cancer cell E_01_0060 PCR Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. Immunohistochemical staining Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. PCR EZH2 Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. 28811072 chr16 81236 83236 NPRL3 One globin gene cluster, linked to the gene NPRL3, is preserved in all vertebrates, including a gene cluster encoding the highly divergent globins from jawless vertebrates. human High+Lowthroughput Evolution of hemoglobin loci and their regulatory elements 否 erythroid cell E_01_0061 One globin gene cluster, linked to the gene NPRL3, is preserved in all vertebrates, including a gene cluster encoding the highly divergent globins from jawless vertebrates. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq One globin gene cluster, linked to the gene NPRL3, is preserved in all vertebrates, including a gene cluster encoding the highly divergent globins from jawless vertebrates. Immunohistochemical staining One globin gene cluster, linked to the gene NPRL3, is preserved in all vertebrates, including a gene cluster encoding the highly divergent globins from jawless vertebrates. NPRL3 One globin gene cluster, linked to the gene NPRL3, is preserved in all vertebrates, including a gene cluster encoding the highly divergent globins from jawless vertebrates. 28810932 chr7 148804688 148806688 EZH2 RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. human CCA High+Lowthroughput Long Noncoding RNA NEAT1 Promotes Growth and Metastasis of Cholangiocarcinoma Cells 否 cholangiocarcinoma Cholangiocarcinoma Cell E_01_0062 qRT-PCR,ChIP,Western blot RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. Immunohistochemical staining RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. qRT-PCR,ChIP,Western blot EZH2 RIP and ChIP assays suggest that NEAT1 is recruited to the E-cadherin promoter by EZH2 (enhancer of zeste homolog 2), where it represses E-cadherin expression. These findings indicate that NEAT1 exerts oncogenic effects in CCA. 28796375 chr7 148804611 148806611 EZH2 Consequently, we find that EZH2 promotes LA cell invasion and metastasis by inhibiting SPRY4-IT1 expression. This article is protected by copyright. human LA High+Lowthroughput Effects of long noncoding RNA SPRY4-IT1-mediated EZH2 on the invasion and migration of lung adenocarcinoma 否 lung adenocarcinoma lung adenocarcinoma (LA) cell E_01_0063 Western blot,RT-qPCR Consequently, we find that EZH2 promotes LA cell invasion and metastasis by inhibiting SPRY4-IT1 expression. This article is protected by copyright. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Consequently, we find that EZH2 promotes LA cell invasion and metastasis by inhibiting SPRY4-IT1 expression. This article is protected by copyright. Immunohistochemical staining Consequently, we find that EZH2 promotes LA cell invasion and metastasis by inhibiting SPRY4-IT1 expression. This article is protected by copyright. Western blot,RT-qPCR EZH2 Consequently, we find that EZH2 promotes LA cell invasion and metastasis by inhibiting SPRY4-IT1 expression. This article is protected by copyright. 28795320 chr7 148804483 148806483 EZH2 Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/b-catenin signaling pathway in laryngeal carcinoma. human Laryngeal carcinoma High+Lowthroughput EZH2 promotes cell proliferation by regulating the expression of RUNX3 in laryngeal carcinoma 否 laryngeal carcinoma laryngeal carcinoma cell E_01_0064 Western blot,qRT-PCR Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/b-catenin signaling pathway in laryngeal carcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/b-catenin signaling pathway in laryngeal carcinoma. Immunohistochemical staining Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/b-catenin signaling pathway in laryngeal carcinoma. Western blot,qRT-PCR EZH2 Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/b-catenin signaling pathway in laryngeal carcinoma. 28774779 chr12 57092763 57094763 STAT6 Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages. human High+Lowthroughput Extensive and functional overlap of the STAT6 and RXR cistromes in the active enhancer repertoire of human CD14+ monocyte derived differentiating macrophages 否 macrophage E_01_0065 ChIP,ChIP-seq,RNA-Seq,qPCR Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages. Immunohistochemical staining Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages. ChIP,ChIP-seq,RNA-Seq,qPCR STAT6 Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages. 28763207 chr7 148804454 148806454 EZH2 human High+Lowthroughput Inhibition of Human Enhancer of Zeste Homolog 2 with Tambjamine Analogs 否 E_01_0066 Immunofluorescence staining Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Immunohistochemical staining Immunofluorescence staining SET,AEBP2 EZH2 28722764 chr7 148804258 148806258 EZH2 We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. human High+Lowthroughput 12-O-tetradecanoylphorbol-13-acetate and EZH2 inhibition: A novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells 否 Rhabdomyosarcoma myocyte E_01_0067 Western blot,Real-Time PCR We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. Immunohistochemical staining We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. Western blot,Real-Time PCR EZH2 We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. 28718381 chr7 148804593 148806593 EZH2 Third, the involvement of EZH2 and epigenetic changes as shown in this study lends further support for the notion that endometriosis is an epigenetic disease79 and justifies the use of HDACIs as therapeutics for endometriosis. human Ectopic endometrial High+Lowthroughput Histological and Immunohistochemical Characterization of the Similarity and Difference Between Ovarian Endometriomas and Deep Infiltrating Endometriosis 否 Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) endothelial cell E_01_0068 immunostaining Third, the involvement of EZH2 and epigenetic changes as shown in this study lends further support for the notion that endometriosis is an epigenetic disease79 and justifies the use of HDACIs as therapeutics for endometriosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Third, the involvement of EZH2 and epigenetic changes as shown in this study lends further support for the notion that endometriosis is an epigenetic disease79 and justifies the use of HDACIs as therapeutics for endometriosis. Immunohistochemical staining Third, the involvement of EZH2 and epigenetic changes as shown in this study lends further support for the notion that endometriosis is an epigenetic disease79 and justifies the use of HDACIs as therapeutics for endometriosis. immunostaining EZH2 Third, the involvement of EZH2 and epigenetic changes as shown in this study lends further support for the notion that endometriosis is an epigenetic disease79 and justifies the use of HDACIs as therapeutics for endometriosis. 28681918 chr7 148804320 148806320 EZH2 Human gene of enhancer of zeste homolog 2 (EZH2) was originally found to encode a histone methyltransferase forming the catalytic component of the polycomb repressive complex-2, thus exerting functional regulations on epigenetic silencing during the process of cell fate decisions human Cervical epithelial High+Lowthroughput MicroRNA-137 is negatively associated with clinical outcome and regulates tumor development through EZH2 in cervical cancer 否 cervical cancer CC cell line E_01_0069 qPCR,Dual-luciferase reporter assay Human gene of enhancer of zeste homolog 2 (EZH2) was originally found to encode a histone methyltransferase forming the catalytic component of the polycomb repressive complex-2, thus exerting functional regulations on epigenetic silencing during the process of cell fate decisions Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Human gene of enhancer of zeste homolog 2 (EZH2) was originally found to encode a histone methyltransferase forming the catalytic component of the polycomb repressive complex-2, thus exerting functional regulations on epigenetic silencing during the process of cell fate decisions Immunohistochemical staining Human gene of enhancer of zeste homolog 2 (EZH2) was originally found to encode a histone methyltransferase forming the catalytic component of the polycomb repressive complex-2, thus exerting functional regulations on epigenetic silencing during the process of cell fate decisions qPCR,Dual-luciferase reporter assay EZH2 Human gene of enhancer of zeste homolog 2 (EZH2) was originally found to encode a histone methyltransferase forming the catalytic component of the polycomb repressive complex-2, thus exerting functional regulations on epigenetic silencing during the process of cell fate decisions 28681114 chr7 148804493 148806493 EZH2 Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. human Tumor High+Lowthroughput Predicting the Correlation of EZH2 and Cancer Stem Cell Markers in Esophageal Squamous Cell Carcinoma 否 Esophageal Squamous Cell Carcinoma Cancer Stem Cell E_01_0070 qRT-PCR Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. qRT-PCR EZH2 Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. 28462489 chr5 179729425 179731425 MAML1 In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. human Tumor High+Lowthroughput Role of MAML1 and MEIS1 in Esophageal Squamous Cell Carcinoma Depth of Invasion 否 esophageal squamous cell carcinoma tumor cell E_01_0071 qRT-PCR In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. qRT-PCR MAML1,MEIS1 In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients.;In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. 28442495 chr13 27958465 27960465 CDX2 CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. human High+Lowthroughput Aspirin prevents NF-κB activation and CDX2 expression stimulated by acid and bile salts in oesophageal squamous cells of patients with Barrett's oesophagus 否 Esophageal Diseases oesophageal squamous cell E_01_0072 Western blot CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. Immunohistochemical staining CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. Western blot CDX2 CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. 28027119 chr4 108044503 108046503 LEF1 Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with b-catenin but has not been studied in DTF human Soft High+Lowthroughput Comparison of β-Catenin and LEF1 Immunohistochemical Stains in Desmoid-type Fibromatosis and its Selected Mimickers, With Unexpected Finding of LEF1 Positivity in Scars 否 desmoid-type fibromatosis E_01_0073 Immunohistochemical staining Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with b-catenin but has not been studied in DTF Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with b-catenin but has not been studied in DTF Immunohistochemical staining Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with b-catenin but has not been studied in DTF Immunohistochemical staining LEF1 Lymphoid enhancer-factor 1 (LEF1), a recently emerged marker, is part of the Wnt pathway with b-catenin but has not been studied in DTF 27997051 chr7 44101517 44103517 AEBP1 Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes human Hippocampal High+Lowthroughput Association of adipocyte enhancer-binding protein 1 with Alzheimer's disease pathology in human hippocampi 否 Alzheimer’s disease smooth muscle cell line E_01_0074 Western blot Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes Immunohistochemical staining Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes Western blot AEBP1 Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes 27845419 chr7 87500277 87502277 ABCB1 These results suggest that genetic variation in ABCC1 and ABCB1 may contribute to irinotecan-induced neutropenia by altering expression of transporters involved in irinotecan metabolite disposition. human Liver High+Lowthroughput ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia 是 rs12720066,rs6498588 Neutropenia Hep G2 cell E_01_0075 Enhancer Assay These results suggest that genetic variation in ABCC1 and ABCB1 may contribute to irinotecan-induced neutropenia by altering expression of transporters involved in irinotecan metabolite disposition. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that genetic variation in ABCC1 and ABCB1 may contribute to irinotecan-induced neutropenia by altering expression of transporters involved in irinotecan metabolite disposition. Immunohistochemical staining These results suggest that genetic variation in ABCC1 and ABCB1 may contribute to irinotecan-induced neutropenia by altering expression of transporters involved in irinotecan metabolite disposition. Enhancer Assay ABCB1 These results suggest that genetic variation in ABCC1 and ABCB1 may contribute to irinotecan-induced neutropenia by altering expression of transporters involved in irinotecan metabolite disposition. 28860350 chr2 43219398 43221398 ZFP36L2 Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; Dna hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancerassociated Scc suppressor human Non-malignant oesophagus High+Lowthroughput Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas 否 Oesophageal squamous cell carcinoma (OScc) and adenocarcinoma (Oac) squamous cell line E_01_0076 ChIP-seq,WGBS Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; Dna hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancerassociated Scc suppressor Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; Dna hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancerassociated Scc suppressor Immunohistochemical staining Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; Dna hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancerassociated Scc suppressor ChIP-seq,WGBS ZFP36L2 Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; Dna hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancerassociated Scc suppressor 31975641 chr1 118880199 118882199 TBX15 Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk. human bone marrow High+Lowthroughput Osteoporosis- and obesity-risk interrelationships: an epigenetic analysis of GWAS-derived SNPs at the developmental gene TBX15 是 rs61730011,rs984222,rs1106529,rs9659323,rs12742627,rs961470,rs17023223 Osteoporosis cementoblast E_01_0077 RNA SEQ, GWAS derived SNPs and LD analysis Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk. Immunohistochemical staining Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk. RNA-seq，GWAS衍生的SNPs和LD分析 TBX15 Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk. 31969149 chr1 8001716 8003716 ERRFI1 The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. human lung High+Lowthroughput An integrated analysis of public genomic data unveils a possible functional mechanism of psoriasis risk via a long-range ERRFI1 enhancer 是 rs72635708 psoriasis IMR-90 cell E_01_0078 ChIP-seq The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. Immunohistochemical staining The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. ChIP-seq ERRFI1 The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. 31967103 chr7 148804333 148806333 EZH2 We tested UNC1999, a small molecule inhibitor that blocks enhancer of zeste homolog 2, an enzyme that maintains closed polycomb chromatin. human kidney High+Lowthroughput Site-directed targeting of transcriptional activation-associated proteins to repressed chromatin restores CRISPR activity 否 HEK293 cell E_01_0079 Transfection, luciferase assay, flow cytometry, chip qPCR, We tested UNC1999, a small molecule inhibitor that blocks enhancer of zeste homolog 2, an enzyme that maintains closed polycomb chromatin. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We tested UNC1999, a small molecule inhibitor that blocks enhancer of zeste homolog 2, an enzyme that maintains closed polycomb chromatin. Immunohistochemical staining We tested UNC1999, a small molecule inhibitor that blocks enhancer of zeste homolog 2, an enzyme that maintains closed polycomb chromatin. 转染，荧光素酶分析，流式细胞术，ChIP-qPCR， EZH2 We tested UNC1999, a small molecule inhibitor that blocks enhancer of zeste homolog 2, an enzyme that maintains closed polycomb chromatin. 31963554 chr10 52311442 52313442 DKK1 Taken together, these observations suggest that 1,25D3 promotes the mineralization of osteoblasts through activation of DKK1 followed by an increase of C/EBPβ. human Bone, mesenchymal High+Lowthroughput DKK1 Induced by 1,25D3 Is Required for the Mineralization of Osteoblasts 否 Osteoporosis osteogenitorcell,cementoblast，SaOS2 cell E_01_0080 QPCR, Western blot, immunofluorescence, luciferase assay, chromatin immunoprecipitation assay Taken together, these observations suggest that 1,25D3 promotes the mineralization of osteoblasts through activation of DKK1 followed by an increase of C/EBPβ. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, these observations suggest that 1,25D3 promotes the mineralization of osteoblasts through activation of DKK1 followed by an increase of C/EBPβ. Immunohistochemical staining Taken together, these observations suggest that 1,25D3 promotes the mineralization of osteoblasts through activation of DKK1 followed by an increase of C/EBPβ. qPCR，Western Blot，免疫荧光，荧光素酶分析，染色质免疫沉淀分析 DKK1 Taken together, these observations suggest that 1,25D3 promotes the mineralization of osteoblasts through activation of DKK1 followed by an increase of C/EBPβ. 31961892 chr11 55334650 55336650 Atox1 Nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer mouse colon High+Lowthroughput Nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer 否 Colon cancer SW480 cell E_01_0081 Immunofluorescence, Western blot, transfection, cell colony assay Nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer Immunohistochemical staining Nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer 免疫荧光，Western blot，转染，细胞集落实验 Atox1 Nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer 31954402 chr7 148804633 148806633 EZH2 Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection. human blood High+Lowthroughput Differential expression of microRNA, miR-150 and enhancer of zeste homolog 2 (EZH2) in peripheral blood cells as early prognostic markers of severe forms of dengue 否 dengue fever E_01_0082 qRT-PCR Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection. Immunohistochemical staining Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection. qRT-PCR EZH2 Expression of enhancer of zeste homolog 2 (EZH2) was significantly (P < 0.01) down regulated indicating that genes involved in epigenetic regulation are also differentially expressed in SD patients during the early stage of infection. 31953940 chr4 108045068 108047068 LEF1 LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs. human High+Lowthroughput Immunohistochemical Expression of Lymphoid Enhancer Binding Factor 1 in CD5-Positive Marginal Zone, Lymphoplasmacytic, and Follicular Lymphomas. 否 Lymphoplasmacytoma, follicular lymphoma tumor cell E_01_0083 Immunohistochemistry, flow cytometry, fluorescence in situ hybridization, QRT PCR LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs. Immunohistochemical staining LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs. 免疫组化，流式细胞术，荧光原位杂交技术，qRT-PCR LEF1 LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs. 31953319 chr22 39516679 39518679 ATF4 Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ. human skeletal muscle High+Lowthroughput Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ 否 Skeletal muscle atrophy mouse cell of skeletal muscle E_01_0084 Western blot, transfection, qPCR, agarose gel electrophoresis Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ. Immunohistochemical staining Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ. Western Blot，转染，qPCR，琼脂糖凝胶电泳 ATF4 Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ. 31952907 chr7 148804371 148806371 EZH2 Taken together, EZH2 in CD4 T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4 T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4 T cells. Defective EZH2 in CD4 T cells might contribute to Treg deficiency in RA. human Connective tissue, peripheral blood High+Lowthroughput EZH2 deficiency attenuates Treg differentiation in rheumatoid arthritis 否 Rheumatoid arthritis synovial cell，peripheral blood mononuclear cell，Jurkat T cell E_01_0085 Western blot，RT-qPCR Taken together, EZH2 in CD4 T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4 T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4 T cells. Defective EZH2 in CD4 T cells might contribute to Treg deficiency in RA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, EZH2 in CD4 T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4 T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4 T cells. Defective EZH2 in CD4 T cells might contribute to Treg deficiency in RA. Immunohistochemical staining Taken together, EZH2 in CD4 T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4 T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4 T cells. Defective EZH2 in CD4 T cells might contribute to Treg deficiency in RA. Western blot，RT-qPCR EZH2 Taken together, EZH2 in CD4 T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4 T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4 T cells. Defective EZH2 in CD4 T cells might contribute to Treg deficiency in RA. 31951295 chr15 88633030 88635030 ISG20 Our findings suggest that ISG20 exerts the anti-HBV activity by acting as a putative repressor binding to the HBV EnhII/Cp region. human liver High+Lowthroughput Antiviral activity of interferon-stimulated gene 20, as a putative repressor binding to hepatitis B virus enhancer II and core promoter 否 hepatitis B HepG2，HepG2 NTCP，HepAD38 cell E_01_0086 Immunohistochemistry, luciferase analysis, transfection, Southern blot, Northern blot, Western blot, RT-PCR, chromatin immunoprecipitation analysis, microarray data analysis Our findings suggest that ISG20 exerts the anti-HBV activity by acting as a putative repressor binding to the HBV EnhII/Cp region. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings suggest that ISG20 exerts the anti-HBV activity by acting as a putative repressor binding to the HBV EnhII/Cp region. Immunohistochemical staining Our findings suggest that ISG20 exerts the anti-HBV activity by acting as a putative repressor binding to the HBV EnhII/Cp region. 免疫组化，荧光素酶分析，转染，Southern blot ，Northern blot，Western blot，RT-PCR ，染色质免疫沉淀分析，微阵列数据分析 ISG20 Our findings suggest that ISG20 exerts the anti-HBV activity by acting as a putative repressor binding to the HBV EnhII/Cp region. 31938642 chr9 81581120 81583120 TLE1 Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study human High+Lowthroughput Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study 否 Soft tissue sarcoma E_01_0087 Immunohistochemistry Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study Immunohistochemical staining Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study 免疫组化 TLE1 Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study 31937612 chr5 69232027 69234027 CDK7 Targeting Super-Enhancer-Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor human bone High+Lowthroughput Targeting Super-Enhancer-Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor 否 Osteosarcoma SJSA-1 cell，U2-OS cell，HOS cell，G-292 cell，MNNG/HOS cell，143B cell，MG-63 cell，cementoblast E_01_0088 Chromatin immunoprecipitation, microarray, transfection, cell viability assay, Transwell, Western blot, RT qPCR Targeting Super-Enhancer-Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Targeting Super-Enhancer-Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor Immunohistochemical staining Targeting Super-Enhancer-Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor 染色质免疫沉淀，微阵列，转染，细胞活力检测，Transwell，Western blot，RT-qPCR CDK7 Targeting Super-Enhancer-Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor 31933869 chr11 113406893 113408893 DRD2 This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD. human Peripheral blood High+Lowthroughput Functional tag SNPs inside the DRD2 gene as a genetic risk factor for major depressive disorder in the Chinese Han population 是 rs4648317,rs7131056 Major depressive disorder peripheral blood mononuclear cell E_01_0089 PCR This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD. Immunohistochemical staining This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD. PCR DRD2 This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD. 31933740 chr9 81580946 81582946 TLE1 TLE1 is a specific and sensitive diagnostic immunomarker for SS and can be helpful to distinguish SS from other mesenchymal neoplasms. human High+Lowthroughput Transducer-like enhancer of split 1 (TLE1) as a novel biomarker for diagnosis of synovial sarcoma correlates with translocation t(X;18): a study of 155 cases in China 否 Synovial sarcoma E_01_0090 Immunohistochemistry, fluorescence in situ hybridization TLE1 is a specific and sensitive diagnostic immunomarker for SS and can be helpful to distinguish SS from other mesenchymal neoplasms. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TLE1 is a specific and sensitive diagnostic immunomarker for SS and can be helpful to distinguish SS from other mesenchymal neoplasms. Immunohistochemical staining TLE1 is a specific and sensitive diagnostic immunomarker for SS and can be helpful to distinguish SS from other mesenchymal neoplasms. 免疫组化，荧光原位杂交 TLE1 TLE1 is a specific and sensitive diagnostic immunomarker for SS and can be helpful to distinguish SS from other mesenchymal neoplasms. 31929803 chr4 108044497 108046497 LEF1 We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level. human High+Lowthroughput Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients 否 Acute myeloid leukemia E_01_0091 RT qPCR, ELISA We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level. Immunohistochemical staining We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level. RT-qPCR，联酶免疫吸附反应 LEF1 We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level. 31928966 chr6 10978082 10980082 ELOVL2 rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression human liver High+Lowthroughput rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression 是 rs953413 liver cancer HepG2 cell E_01_0092 As qPCR, chip SEQ, gene knockdown, QRT PCR, chromatin immunoprecipitation, luciferase reporter rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression Immunohistochemical staining rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression AS-qPCR，ChIP-seq，基因敲除，qRT-PCR，染色质免疫沉淀，荧光素酶报告基因 ELOVL2 rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression 31914533 chr19 19142448 19144448 MEF2B The expression of MEF2B in MCL is related to the pathological subtypes, structural subtypes and the expression of SOX11, but not to the proliferation and prognosis. human High+Lowthroughput Expression of myocyte enhancer factor 2B in mantle cell lymphoma and its clinical significance 否 Mantle cell lymphoma E_01_0093 He staining, immunohistochemistry, fluorescence in situ hybridization The expression of MEF2B in MCL is related to the pathological subtypes, structural subtypes and the expression of SOX11, but not to the proliferation and prognosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression of MEF2B in MCL is related to the pathological subtypes, structural subtypes and the expression of SOX11, but not to the proliferation and prognosis. Immunohistochemical staining The expression of MEF2B in MCL is related to the pathological subtypes, structural subtypes and the expression of SOX11, but not to the proliferation and prognosis. HE染色，免疫组化，荧光原位杂交 MEF2B The expression of MEF2B in MCL is related to the pathological subtypes, structural subtypes and the expression of SOX11, but not to the proliferation and prognosis. 31914083 chr5 51380063 51382063 ISL1 ISL1 promotes cardiomyocyte differentiation and plays important roles in heart development. human High+Lowthroughput Correlations between ISL1 rs1017 polymorphism and congenital heart disease risk: A PRISMA-compliant meta-analysis 是 rs1017 Congenital heart disease cardiac muscle cell (sensu Arthopoda) E_01_0094 ISL1 promotes cardiomyocyte differentiation and plays important roles in heart development. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ISL1 promotes cardiomyocyte differentiation and plays important roles in heart development. Immunohistochemical staining ISL1 promotes cardiomyocyte differentiation and plays important roles in heart development. ISL1 ISL1 promotes cardiomyocyte differentiation and plays important roles in heart development. 31910882 chr11 306685 308685 IFITM1 Increased expression of the IFITM1 gene is required for LPS-stimulated hMSC migration. human bone marrow High+Lowthroughput Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells 否 hMSC cell E_01_0095 QRT PCR, ELISA, Western blot, immunocytochemistry, chromatin immunoprecipitation PCR, chip SEQ, scratch assay, gene knockdown, luciferase reporter assay Increased expression of the IFITM1 gene is required for LPS-stimulated hMSC migration. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Increased expression of the IFITM1 gene is required for LPS-stimulated hMSC migration. Immunohistochemical staining Increased expression of the IFITM1 gene is required for LPS-stimulated hMSC migration. qRT-PCR，酶联免疫吸附试验，Western blot，免疫细胞化学，染色质免疫沉淀PCR，ChIP-seq，划痕实验，基因敲降，荧光素酶报告试验 IFITM1 Increased expression of the IFITM1 gene is required for LPS-stimulated hMSC migration. 31902945 chr22 27745785 27747785 MN1 Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12) human bone marrow High+Lowthroughput Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12) 否 Myeloid neoplasms Bone marrow monocytes E_01_0096 Whole genome sequencing, RT-PCR, fluorescence in situ hybridization, Sanger sequencing Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12) Immunohistochemical staining Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12) 全基因组测序，RT-PCR，荧光原位杂交，sanger测序 MN1 Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12) 31900258 chr5 1250197 1252197 TERT Epigenetically cotargeting Brd4 and Cdks suppresses human neuroblastoma with TERT overexpression by inhibiting the TERT-associated gene expression networks. human High+Lowthroughput 否 Neuroblastoma neuroblastoma cells，SK-N-AS cell E_01_0097 Chip – qPCR, RT qPCR, Western blot, cell viability assay Epigenetically cotargeting Brd4 and Cdks suppresses human neuroblastoma with TERT overexpression by inhibiting the TERT-associated gene expression networks. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Epigenetically cotargeting Brd4 and Cdks suppresses human neuroblastoma with TERT overexpression by inhibiting the TERT-associated gene expression networks. Immunohistochemical staining Epigenetically cotargeting Brd4 and Cdks suppresses human neuroblastoma with TERT overexpression by inhibiting the TERT-associated gene expression networks. ChIP–qPCR，RT-qPCR，Western blot，细胞活力检测 TERT Epigenetically cotargeting Brd4 and Cdks suppresses human neuroblastoma with TERT overexpression by inhibiting the TERT-associated gene expression networks. 31899875 chr14 100776332 100778332 MEG3 Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P. human ovarian follicle High+Lowthroughput MEG3/MIR-376B-3P/HMGA2 axis is involved in pituitary tumor invasiveness 否 Pituitary tumors E_01_0098 Dual luciferase reporter assay, immunofluorescence, IHC, RT qPCR, Western blot, flow cytometry, TUNEL staining, transfection, cell viability assay, Transwell, scratch assay Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P. Immunohistochemical staining Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P. 双荧光素酶报告基因，免疫荧光，，免疫组化，RT-qPCR，Western blot，流式细胞术，TUNEL染色，转染，细胞活力检测，Transwell，划痕实验 MEG3 Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P. 31897846 chr19 2974615 2976615 TLE6 Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations human High+Lowthroughput Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations 否 Infertility E_01_0099 Whole exome sequencing, Sanger sequencing Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations Immunohistochemical staining Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations 全外显子组测序，Sanger测序 TLE6 Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations 31897220 chr1 6098734 6100734 CHD5 In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer. human Stomach, cervix High+Lowthroughput Clinical significance of chromatin remodeling factor CHD5 expression in gastric cancer 否 gastric cancer AGS cell, KATO III cell, MKN45 cell, NCI-N87 cell, NUGC-3 cell, OCUM‑1 cell,HeLa cell E_01_0100 Immunohistochemistry, scratch assay, cell viability assay, Transwell, Western blot, RT ＾ PCR In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer. Immunohistochemical staining In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer. 免疫组化，划痕实验，细胞活力检测，Transwell，western blot，RT‑PCR CHD5 In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer. 31897216 chr4 7751333 7753333 AFAP1-AS1 In conclusion, AFAP1-AS1 accelerates the proliferative and metastatic abilities of A549/DDP cells, whereas inhibits the apoptosis of A549/DDP cells, by interacting with EZH2 to activate the PI3K/AKT pathway; thus, inducing DDP resistance in NSCLC. human lung High+Lowthroughput AFAP1-AS1 induces cisplatin resistance in non-small cell lung cancer through PI3K/AKT pathway 否 Non small cell lung cancer A549 cell E_01_0101 RNA immunoprecipitation, flow cytometry, Western blot, Transwell, RT ‐qpcr In conclusion, AFAP1-AS1 accelerates the proliferative and metastatic abilities of A549/DDP cells, whereas inhibits the apoptosis of A549/DDP cells, by interacting with EZH2 to activate the PI3K/AKT pathway; thus, inducing DDP resistance in NSCLC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, AFAP1-AS1 accelerates the proliferative and metastatic abilities of A549/DDP cells, whereas inhibits the apoptosis of A549/DDP cells, by interacting with EZH2 to activate the PI3K/AKT pathway; thus, inducing DDP resistance in NSCLC. Immunohistochemical staining In conclusion, AFAP1-AS1 accelerates the proliferative and metastatic abilities of A549/DDP cells, whereas inhibits the apoptosis of A549/DDP cells, by interacting with EZH2 to activate the PI3K/AKT pathway; thus, inducing DDP resistance in NSCLC. RNA免疫沉淀，流式细胞术，Western blot，Transwell，RT‑qPCR AFAP1-AS1 In conclusion, AFAP1-AS1 accelerates the proliferative and metastatic abilities of A549/DDP cells, whereas inhibits the apoptosis of A549/DDP cells, by interacting with EZH2 to activate the PI3K/AKT pathway; thus, inducing DDP resistance in NSCLC. 31893185 chr9 81580729 81582729 TLE1 TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies. human High+Lowthroughput Is TLE1 Expression Limited to Synovial Sarcoma? Our Experience at Shifa International Hospital, Pakistan 否 Synovial sarcoma E_01_0102 Immunohistochemistry TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies. Immunohistochemical staining TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies. 免疫组化 TLE1 TLE1 may be a reliable immunostain for diagnosing SS, but its expression is not limited to SS. Its expression should be interpreted in the light of morphological features and a panel of antibodies. 31892537 chr10 102103573 102105573 LDB1 Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer-promoter interactions. human blood High+Lowthroughput Crystal structure of human LDB1 in complex with SSBP2 否 erythrocyte E_01_0103 pull-down Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer-promoter interactions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer-promoter interactions. Immunohistochemical staining Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer-promoter interactions. pull-down LDB1 Our structural and biochemical data provide a much-anticipated structural basis for understanding how LDB1 and the LDB1/SSBP interactions form the structural core of diverse complexes mediating cell choice decisions and long-range enhancer-promoter interactions. 31891591 chr7 148804482 148806482 EZH2 A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy human High+Lowthroughput A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy 否 epilepsy E_01_0104 Western blot，qRT-PCR，LC-MS A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy Immunohistochemical staining A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy Western blot，qRT-PCR，LC-MS EZH2 A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy 31890812 chr2 60447611 60449611 BCL11A Expression analysis data of BCL11A and γ-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion. human Kidney, peripheral blood, bone marrow High+Lowthroughput Expression analysis data of BCL11A and γ-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion 否 β- Thalassemia disorders HEK293T cell， KU812 cell，KG-1 cell E_01_0105 Agarose gel electrophoresis, QRT PCR Expression analysis data of BCL11A and γ-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression analysis data of BCL11A and γ-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion. Immunohistochemical staining Expression analysis data of BCL11A and γ-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion. 琼脂糖凝胶电泳， qRT-PCR BCL11A Expression analysis data of BCL11A and γ-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion. 31888703 chr3 12284215 12286215 PPARG Enhancer polymorphism rs10865710 associated with traumatic sepsis is a regulator of PPARG gene expression human High+Lowthroughput Enhancer polymorphism rs10865710 associated with traumatic sepsis is a regulator of PPARG gene expression 是 rs10865710 Traumatic sepsis E_01_0106 Western blot, dual luciferase gene reporter Enhancer polymorphism rs10865710 associated with traumatic sepsis is a regulator of PPARG gene expression Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer polymorphism rs10865710 associated with traumatic sepsis is a regulator of PPARG gene expression Immunohistochemical staining Enhancer polymorphism rs10865710 associated with traumatic sepsis is a regulator of PPARG gene expression Western blot，双荧光素酶基因报告 PPARG Enhancer polymorphism rs10865710 associated with traumatic sepsis is a regulator of PPARG gene expression 31886719 chr11 100684149 100686149 ARHGAP42 First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription. human Aortic smooth muscle, bronchial smooth muscle High+Lowthroughput Transcriptional and posttranscriptional regulation of the SMC-selective blood pressure-associated gene, ARHGAP42 是 rs604723 Blood pressure regulation HUAOSMC cell，HUBRSMC cell E_01_0107 Luciferase assay, immunoprecipitation, QRT PCR, chromatin immunoprecipitation assay, Western blot, electrophoretic mobility shift assay, immunofluorescence First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription. Immunohistochemical staining First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription. 荧光素酶分析，免疫沉淀，qRT-PCR，染色质免疫沉淀实验，Western blot，电泳迁移率分析，免疫荧光 ARHGAP42 First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription. 31886200 chr7 148804829 148806829 EZH2 Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution. human bone marrow High+Lowthroughput Aberrant Expression of EZH2 in Pediatric Patients with Myelodysplastic Syndrome: A Potential Biomarker of Leukemic Evolution 否 Pediatric myelodysplastic syndrome bone marrow cell E_01_0108 qRT–PCR Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution. Immunohistochemical staining Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution. qRT–PCR EZH2 Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution. 31882553 chr19 15232668 15234668 BRD4 Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma. human lymph High+Lowthroughput BRD4-Regulated Molecular Targets in Mantle Cell Lymphoma: Insights into Targeted Therapeutic Approach 否 Mantle cell lymphoma JVM-2 cell，MINO cell，Z138 cell，KPUM-YY1 cell E_01_0109 Cell viability assay, Western blot, QRT PCR, chromatin immunoprecipitation Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma. Immunohistochemical staining Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma. 细胞活力检测，Western blot，qRT-PCR，染色质免疫沉淀 BRD4 Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma. 31878072 chr1 153659104 153661104 ILF2 Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein. human Kidney, peripheral blood High+Lowthroughput Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects 否 antiviral HEK293T cell、Vero cell、RD cell，thp-1 cell E_01_0110 RT qPCR, Western blot, CO immunoprecipitation, immunofluorescence Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein. Immunohistochemical staining Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein. RT-qPCR，Western blot，免疫共沉淀，免疫荧光 ILF2 Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein. 31866294 chr7 148804551 148806551 EZH2 Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2. human colon High+Lowthroughput Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2 否 tumour HCT116 cell E_01_0111 Fluorescence polarization assay, Western blot, CO immunoprecipitation Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2. Immunohistochemical staining Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2. 荧光偏振分析，Western Blot，共免疫沉淀 EZH2 Structural Basis of the Interaction Between Ubiquitin Specific Protease 7 and Enhancer of Zeste Homolog 2. 31866047 chr20 59860441 59862441 SYCP2 SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility human lymph High+Lowthroughput SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility 是 rs568645874,rs199662252,rs45568532,rs551180067,rs11549332 Lymphoblast E_01_0112 QRT PCR, Western blot, Sanger sequencing, PAS staining, hematoxylin staining SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility Immunohistochemical staining SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility qRT-PCR，Western Blot，Sanger测序，PAS染色，苏木精染色 SYCP2 SYCP2 Translocation-Mediated Dysregulation and Frameshift Variants Cause Human Male Infertility 31864713 chr7 44101569 44103569 AEBP1 Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis human brain High+Lowthroughput Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis 否 Gliomas U87MG cell，U251 MG cell E_01_0113 Western blot, immunohistochemistry, QRT PCR, cell viability assay, Transwell, immunofluorescence, flow cytometry Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis Immunohistochemical staining Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis Western-blot，免疫组化，qRT-PCR，细胞活力检测，Transwell，免疫荧光，流式细胞术 AEBP1 Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis 31861475 chr9 36570240 36572240 MELK Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma human bile duct High+Lowthroughput Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma 否 Intrahepatic cholangiocarcinoma iCCA cell E_01_0114 RT-PCR, immunohistochemistry Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma Immunohistochemical staining Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma RT-PCR，免疫组织化学 MELK Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma 31860165 chr4 52709533 52711533 DANCR The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription human breast High+Lowthroughput The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription 否 mammary cancer breast cancer cells，mammary gland epithelial cell E_01_0115 QRT PCR, cell viability assay, ELISA, Western blot, RNA immunoprecipitation, chromatin immunoprecipitation, Transwell The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription Immunohistochemical staining The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription qRT-PCR，细胞活力检测，ELISA，Western blot，RNA免疫沉淀，染色质免疫沉淀，Transwell DANCR The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription 31858557 chr15 42735912 42737912 TTBK2 Circ-TTBK2/miR-520b/EZH2 axis modulated cell proliferation, apoptosis, and invasion in glioma cell lines, and might serve as potential targets for glioma diagnosis and therapy. human brain High+Lowthroughput Circular RNA TTBK2 promotes the development of human glioma cells via miR-520b/EZH2 axis 否 Gliomas A172 cell，U251 cell，astrocyte cell E_01_0116 Transfection, QRT PCR, Western blot, flow cytometry, Transwell, dual luciferase reporter assay Circ-TTBK2/miR-520b/EZH2 axis modulated cell proliferation, apoptosis, and invasion in glioma cell lines, and might serve as potential targets for glioma diagnosis and therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Circ-TTBK2/miR-520b/EZH2 axis modulated cell proliferation, apoptosis, and invasion in glioma cell lines, and might serve as potential targets for glioma diagnosis and therapy. Immunohistochemical staining Circ-TTBK2/miR-520b/EZH2 axis modulated cell proliferation, apoptosis, and invasion in glioma cell lines, and might serve as potential targets for glioma diagnosis and therapy. 转染，qRT-PCR，Western Blot，流式细胞术，Transwell，双荧光素酶报告分析 TTBK2 Circ-TTBK2/miR-520b/EZH2 axis modulated cell proliferation, apoptosis, and invasion in glioma cell lines, and might serve as potential targets for glioma diagnosis and therapy. 31856860 chr20 50188118 50190118 CEBPB Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. human High+Lowthroughput A longitudinal study highlights shared aspects of the transcriptomic response to cardiogenic and septic shock 否 Cardiogenic and septic shock E_01_0117 RNA sequencing Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. Immunohistochemical staining Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. RNA测序 CEBPB Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend. 31851943 chr19 1606379 1608379 TCF3 Loss-of-function studies of TCF3 confirm the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs. human bone marrow High+Lowthroughput Spatial Genome Re-organization between Fetal and Adult Hematopoietic Stem Cells 否 HPC-7 cell E_01_0118 Dna-fish, Western blot, flow cytometry Loss-of-function studies of TCF3 confirm the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Loss-of-function studies of TCF3 confirm the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs. Immunohistochemical staining Loss-of-function studies of TCF3 confirm the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs. DNA-FISH， Western blot，流式细胞术 TCF7L1 Loss-of-function studies of TCF3 confirm the role of TCF3 in mediating condition-specific enhancer-promoter interactions and gene regulation in fetal HSCs. 31845224 chr2 26345405 26347405 Notch1 Taken together, these data suggest that Notch1 drives ICC formation and proliferation; downregulation of Notch1 induces apoptosis in ICC cells; Notch1 signaling may serve as a novel therapeutic target for the treatment of ICC. mouse gallbladder High+Lowthroughput Notch1 Drives the Formation and Proliferation of Intrahepatic Cholangiocarcinoma 否 Intrahepatic cholangiocarcinoma BC-939 cell，RBE cell E_01_0119 Western blot, flow cytometry, Western blot, immunohistochemistry, immunofluorescence, QRT PCR Taken together, these data suggest that Notch1 drives ICC formation and proliferation; downregulation of Notch1 induces apoptosis in ICC cells; Notch1 signaling may serve as a novel therapeutic target for the treatment of ICC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, these data suggest that Notch1 drives ICC formation and proliferation; downregulation of Notch1 induces apoptosis in ICC cells; Notch1 signaling may serve as a novel therapeutic target for the treatment of ICC. Immunohistochemical staining Taken together, these data suggest that Notch1 drives ICC formation and proliferation; downregulation of Notch1 induces apoptosis in ICC cells; Notch1 signaling may serve as a novel therapeutic target for the treatment of ICC. Western blot， 流式细胞术，Western Blot，免疫组化，免疫荧光，qRT-PCR Notch1 Taken together, these data suggest that Notch1 drives ICC formation and proliferation; downregulation of Notch1 induces apoptosis in ICC cells; Notch1 signaling may serve as a novel therapeutic target for the treatment of ICC. 31843716 chr18 55219904 55221904 TCF4 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells human breast High+Lowthroughput 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells 否 mammary cancer MCF-7 cell，MDA-MB-231 cell E_01_0120 Flow cytometry, immunofluorescence, Western blot 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells Immunohistochemical staining 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells 流式细胞术，免疫荧光，Western blot TCF4 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells 31843273 chr7 148804648 148806648 EZH2 Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. human High+Lowthroughput Overexpression of enhance of Zeste homolog 2 (EZH2) in endometrial carcinoma: An NRG Oncology/Gynecologic Oncology Group Study 否 Endometrial cancer E_01_0121 RT-PCR，Western blot Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. Immunohistochemical staining Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. RT-PCR，Western blot EZH2 Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. 31836590 chr1 145918614 145920614 RBM8A Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. human High+Lowthroughput 1q21.1 deletion and a rare functional polymorphism in siblings with thrombocytopenia-absent radius-like phenotypes 是 rs61746197 Thrombocytopenia, radial hypoplasia E_01_0122 Western blot Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. Immunohistochemical staining Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. Western blot RBM8A Thrombocytopenia-absent radii (TAR) syndrome, characterized by neonatal thrombocytopenia and bilateral radial aplasia with thumbs present, is typically caused by the inheritance of a 1q21.1 deletion and a single-nucelotide polymorphism in RBM8A on the nondeleted allele. 31831267 chr7 148804596 148806596 EZH2 UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. human Cervix, lymph, kidney High+Lowthroughput Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader 否 cancer Hela cell，DB cell，Pfeiffer cell，293T Cell E_01_0123 Western blot, cell viability assay UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. Immunohistochemical staining UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. Western Blot，细胞活力检测 EZH2 UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. 31827084 chrX 113613674 113615674 XACT This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways. human embryo High+Lowthroughput A primate-specific retroviral enhancer wires the XACT lncRNA into the core pluripotency network in humans 否 embryonic stem cell E_01_0124 Rna-fish, RT qPCR, chromatin immunoprecipitation, Western blot, This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways. Immunohistochemical staining This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways. RNA-FISH，RT-qPCR，染色质免疫沉淀，western blot， XACT This ERV was hijacked by younger hominoid-specific ERVs that gave rise to the promoter of XACT, thus wiring its expression to the pluripotency network. This work illustrates how retroviral-derived sequences may intervene in species-specific regulatory pathways. 31826955 chr14 37586693 37588693 FOXA1 Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α-dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer. human breast High+Lowthroughput FOXA1 upregulation promotes enhancer and transcriptional reprogramming in endocrine-resistant breast cancer 否 mammary cancer MCF7L cell，T47D cell，600MPE cell E_01_0125 Western blot, immunohistochemistry, QRT PCR Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α-dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α-dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer. Immunohistochemical staining Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α-dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer. Western blot，免疫组化，qRT-PCR FOXA1 Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α-dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer. 31825847 chr20 64045290 64047290 SOX18 The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs. human ovary High+Lowthroughput A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development 否 oophoroma FT246，FT282，FT318，CaOV3，COV318，EFO21，Kuramochi，FUOV1，OAW28，OV177，OVSAHO，TykNu，UWB1.289 cell E_01_0126 western blot，qRT-PCR The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs. Immunohistochemical staining The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs. western blot，qRT-PCR SOX18 The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs. 31819273 chr7 148804439 148806439 EZH2 Using a hydrophobic tagging approach, we generated MS1943, a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells. Importantly, MS1943 has a profound cytotoxic effect in multiple TNBC cells, while sparing normal cells, and is efficacious in vivo, suggesting that pharmacologic degradation of EZH2 can be advantageous for treating the cancers that are dependent on EZH2. human breast High+Lowthroughput Discovery of a first-in-class EZH2 selective degrader 否 cancer MDA-MB-231，MDA-MB-468，BT549 E_01_0127 Western blot, cell viability assay, crystal violet staining, QRT PCR Using a hydrophobic tagging approach, we generated MS1943, a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells. Importantly, MS1943 has a profound cytotoxic effect in multiple TNBC cells, while sparing normal cells, and is efficacious in vivo, suggesting that pharmacologic degradation of EZH2 can be advantageous for treating the cancers that are dependent on EZH2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using a hydrophobic tagging approach, we generated MS1943, a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells. Importantly, MS1943 has a profound cytotoxic effect in multiple TNBC cells, while sparing normal cells, and is efficacious in vivo, suggesting that pharmacologic degradation of EZH2 can be advantageous for treating the cancers that are dependent on EZH2. Immunohistochemical staining Using a hydrophobic tagging approach, we generated MS1943, a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells. Importantly, MS1943 has a profound cytotoxic effect in multiple TNBC cells, while sparing normal cells, and is efficacious in vivo, suggesting that pharmacologic degradation of EZH2 can be advantageous for treating the cancers that are dependent on EZH2. western blot，细胞活力检测，结晶紫染色，qRT-PCR EZH2 Using a hydrophobic tagging approach, we generated MS1943, a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells. Importantly, MS1943 has a profound cytotoxic effect in multiple TNBC cells, while sparing normal cells, and is efficacious in vivo, suggesting that pharmacologic degradation of EZH2 can be advantageous for treating the cancers that are dependent on EZH2. 31817839 chr1 115283204 115285204 NGF NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE 2 Signaling Axis human ovary High+Lowthroughput NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE 2 Signaling Axis 否 Epithelial ovarian cancer HOSE cell，A2780 cell，SKOV3 cell，OV90 cell，NIH-OVCAR3 cell E_01_0128 Immunohistochemistry, immunocytochemistry, Western blot, QRT PCR, ELISA NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE 2 Signaling Axis Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE 2 Signaling Axis Immunohistochemical staining NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE 2 Signaling Axis 免疫组织化学，免疫细胞化学，Western Blot，qRT-PCR， ELISA NGF NGF-Enhanced Vasculogenic Properties of Epithelial Ovarian Cancer Cells Is Reduced by Inhibition of the COX-2/PGE 2 Signaling Axis 31804013 chr5 151027281 151029281 TNIP1 Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. human Peripheral blood High+Lowthroughput Role of Systemic Lupus Erythematosus Risk Variants With Opposing Functional Effects as a Driver of Hypomorphic Expression of TNIP1 and Other Genes Within a Three-Dimensional Chromatin Network 否 Systemic lupus erythematosus Jurkat cell，THP-1cell E_01_0129 Dual luciferase reporter assay, electrophoretic mobility shift assay, QRT PCR, Western blot, and pulldown Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. Immunohistochemical staining Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. 双荧光素酶报告分析，电泳迁移率分析，qRT-PCR，Western blot，pulldown TNIP1 Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. 31799674 chr12 53959218 53961218 HOTAIR LncRNA HOTAIR activates the expression of NF-κB in myeloma cells and promotes the proliferation of myeloma cells. human bone marrow High+Lowthroughput Effects of lncRNA HOTAIR on proliferation and apoptosis of myeloma cells through NF-κB pathway 否 Myeloma Myeloma cell E_01_0130 QRT PCR, flow cytometry, Western blot, cell viability assay, transfection LncRNA HOTAIR activates the expression of NF-κB in myeloma cells and promotes the proliferation of myeloma cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LncRNA HOTAIR activates the expression of NF-κB in myeloma cells and promotes the proliferation of myeloma cells. Immunohistochemical staining LncRNA HOTAIR activates the expression of NF-κB in myeloma cells and promotes the proliferation of myeloma cells. qRT-PCR，流式细胞术，Western blot，细胞活力检测，转染 HOTAIR LncRNA HOTAIR activates the expression of NF-κB in myeloma cells and promotes the proliferation of myeloma cells. 29861296 chr18 26013138 26015138 SS18 These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations. human Synovial sarcoma High+Lowthroughput The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma 否 Synovial sarcoma (SS) HEK293T LentiX cell E_01_0131 Gene Knockdown,Western Blot,Immunoprecipitations,CRISPR/Cas9,Cell Proliferation Assay,Immunohistochemistry,Chromatin Immunoprecipitation (ChIP),RNA Isolation,RNA-seq,Assay for Transposase-Accessible Chromatin Sequencing (ATAC-seq),ChIP-Seq ,CHIP,Whole Exome Sequencing of Tumors These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations. Immunohistochemical staining These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations. Gene Knockdown,Western Blot,Immunoprecipitations,CRISPR/Cas9,Cell Proliferation Assay,Immunohistochemistry,Chromatin Immunoprecipitation (ChIP),RNA Isolation,RNA-seq,Assay for Transposase-Accessible Chromatin Sequencing (ATAC-seq),ChIP-Seq ,CHIP,Whole Exome Sequencing of Tumors SS18,SMARCB1 These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.;These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations. 29859124 chr1 11009935 11011935 TARDBP Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA. human Nervous High+Lowthroughput Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis 否 Amyotrophic lateral sclerosis (ALS) SH-SY5Y neuroblastoma cell E_01_0132 Immunocytochemistry,RNA-FISH,RIP,PCR,Western blot,qRT-PCR,Real-time qPCR,transfection,Cell Viability Assay Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA. Immunohistochemical staining Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA. Immunocytochemistry,RNA-FISH,RIP,PCR,Western blot,qRT-PCR,Real-time qPCR,transfection,Cell Viability Assay TARDBP Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA. 32517740 chr4 153777966 153779966 SFRP2 We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. human High+Lowthroughput Association between variation of circulating 25-OH vitamin D and methylation of secreted frizzled-related protein 2 in colorectal cancer 否 Colorectal cancer Human colorectal carcinoma cell E_01_0133 PCR We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. Immunohistochemical staining We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. PCR SFRP2 We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. 32517078 chr10 112947720 112949720 TCF7L2 We report here that TCF7L2 transcription factor expression was found to be correlated to blast cell numbers during the progression of the disease. human High+Lowthroughput Embryonic Program Activated during Blast Crisis of Chronic Myelogenous Leukemia (CML) Implicates a TCF7L2 and MYC Cooperative Chromatin Binding 否 Chronic Myelogenous Leukemia K562 cell E_01_0134 QRT-PCR， We report here that TCF7L2 transcription factor expression was found to be correlated to blast cell numbers during the progression of the disease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We report here that TCF7L2 transcription factor expression was found to be correlated to blast cell numbers during the progression of the disease. Immunohistochemical staining We report here that TCF7L2 transcription factor expression was found to be correlated to blast cell numbers during the progression of the disease. QRT-PCR， TCF7L2 We report here that TCF7L2 transcription factor expression was found to be correlated to blast cell numbers during the progression of the disease. 32514254 chr12 56749082 56751082 HSD17B6 HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. human High+Lowthroughput Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma 否 Hepatocellular carcinoma HCC cell E_01_0135 Gene set enrichment analysis，RT‑qPCR，Western blot HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Immunohistochemical staining HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. Gene set enrichment analysis，RT‑qPCR，Western blot HSD17B6 HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1. 29945888 chr11 120233455 120235455 POU2F3 An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017). human High+Lowthroughput POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer 否 Small cell lung cancer (SCLC) SCLC cell E_01_0136 Rna-fish, human SCLC immunohistochemistry, Western blot, RNA SEQ, GSEA, chip SEQ, immunofluorescence staining An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017). Immunohistochemical staining An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017). RNA-FISH,Human SCLC immunohistochemistry,Western blot,RNA-seq,GSEA,ChIP-seq,免疫荧光染色 POU2F3,ASCL1,NEUROD1,INSM1 An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017).;An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017).;An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017).;An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Experiments in genetically engineered mice suggest a pulmonary neuroendocrine cell of origin for SCLC (Semenova et al. 2015), which is supported by the expression of neuroendocrine differentiation markers chromogranin A (CHGA) and insulinoma-associated protein 1 (INSM1) in human SCLC tumors (Gazdar et al. 2017). 29580634 chr5 173229639 173231639 NKX2-5 NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. human Vascular High+Lowthroughput Molecular Basis for Dysregulated Activation of NKX2-5 in the Vascular Remodeling of Systemic Sclerosis 是 rs3095870 scleroderma associated pulmonary hypertensio smooth muscle cell of the pulmonary artery E_01_0137 Western blot,qPCR NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. Immunohistochemical staining NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. Western blot,qPCR NKX2-5 NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. 29579222 chr11 12671903 12673903 TEAD1 TEAD1 is a member of TEA/ATTS domain family transcription regulators with distinct and important roles in VSMC differentiation and in cardiovascular disease human Vascular High+Lowthroughput Molecular Basis for Dysregulated Activation of NKX2-5 in the Vascular Remodeling of Systemic Sclerosis 是 rs3095870 scleroderma associated pulmonary hypertensio smooth muscle cell of the pulmonary artery E_01_0138 Western blot,qPCR TEAD1 is a member of TEA/ATTS domain family transcription regulators with distinct and important roles in VSMC differentiation and in cardiovascular disease Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TEAD1 is a member of TEA/ATTS domain family transcription regulators with distinct and important roles in VSMC differentiation and in cardiovascular disease Immunohistochemical staining TEAD1 is a member of TEA/ATTS domain family transcription regulators with distinct and important roles in VSMC differentiation and in cardiovascular disease Western blot,qPCR TEAD1 TEAD1 is a member of TEA/ATTS domain family transcription regulators with distinct and important roles in VSMC differentiation and in cardiovascular disease 29576612 chr17 42310573 42312573 STAT3 Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity human High+Lowthroughput Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity 否 E_01_0139 EZH2 Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity Immunohistochemical staining Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity EZH2 STAT3 Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity 29572261 chr12 54030375 54032375 HOXC5 Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. human Somatic High+Lowthroughput HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis 否 Tumor somatic cell E_01_0140 Luciferase reporter assay,Western blot,ChIP-Seq,qRT-PCR,3C-qPCR Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. Immunohistochemical staining Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. Luciferase reporter assay,Western blot,ChIP-Seq,qRT-PCR,3C-qPCR HOXC5 Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. 29570423 chr19 19143043 19145043 MEF2B Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. human Lymphoid High+Lowthroughput Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas 否 Lymphomas B cell E_01_0141 Immunohistochemical Staining Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Immunohistochemical staining Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Immunohistochemical Staining MEF2B Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. 29569934 chr17 43751254 43753254 SOST The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. human Bone High+Lowthroughput Computational and functional characterization of four SNPs in the SOST locus associated with osteoporosis 是 rs1230399,rs7220711,rs1107748,rs75901553 osteoporosis Germinal center B-cells E_01_0142 Luciferase reporter assay,ChIP,qPCR The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Immunohistochemical staining The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Luciferase reporter assay,ChIP,qPCR SOST The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. 29563873 chr14 100892224 100894224 MEG8 Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. human High+Lowthroughput MEG8 long noncoding RNA contributes to epigenetic progression of the epithelial-mesenchymal transition of lung and pancreatic cancer cells 否 Lung and pancreatic cancer A549 cell， LC-2/ad cell，Panc1 cell E_01_0143 Quantitative PCR，Cell migration assay，Chromatin immunoprecipitation (ChIP) assays，RNA immunoprecipitation (RIP)，Chromatin isolation by RNA purification (ChIRP) assays Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. Immunohistochemical staining Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. Quantitative PCR，Cell migration assay，Chromatin immunoprecipitation (ChIP) assays，RNA immunoprecipitation (RIP)，Chromatin isolation by RNA purification (ChIRP) assays MEG8 Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. 29563767 chr12 55740444 55742444 GDF11 Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. human High+Lowthroughput GDF11 Antagonizes Psoriasis-like Skin Inflammation via Suppression of NF-κB Signaling Pathway 否 Psoriasiform skin inflammation Mouse leukemic monocyte macrophages E_01_0144 miRNA transfection，Real-Time PCR,Western Blot,Immunofluorescence,ELISA Assays Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. Immunohistochemical staining Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. miRNA transfection，Real-Time PCR,Western Blot,Immunofluorescence,ELISA Assays GDF11 Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. 29563503 chr8 127077409 127079409 PRNCR1 Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. human High+Lowthroughput LncRNA PRNCR1 interacts with HEY2 to abolish miR-448-mediated growth inhibition in non-small cell lung cancer 否 Non small cell lung cancer A549 cell, SK-MES-1 cell, Calu-3 cell，H1299 cell，NHBE cell E_01_0145 Cell transfection,RNA isolation,qRT-PCR analysi, Cell proliferation assays, Transwell assays,Luciferase reporter analysis,RIP assay, Western blot assay Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Immunohistochemical staining Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Cell transfection,RNA isolation,qRT-PCR analysi, Cell proliferation assays, Transwell assays,Luciferase reporter analysis,RIP assay, Western blot assay PRNCR1 HEY2 Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. 29563176 chr16 67559907 67561907 CTCF These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. human blood High+Lowthroughput The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance 否 K562 cell E_01_0146 PCR These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. Immunohistochemical staining These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. PCR CTCF These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. 29563122 chr9 21074270 21076270 IFNB1 We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). human uterus High+Lowthroughput The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers 否 HeLa cell E_01_0147 PCR, Western blot, flow cytometry, immunofluorescence staining We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). Immunohistochemical staining We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). PCR,Western blot,Flow cytometry,免疫荧光染色 IFNB1 We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). 29559957 chr7 99754049 99756049 CYP3A4 The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. human High+Lowthroughput DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression 否 HepG2 cell E_01_0148 Plasmid construction，In vitro methylation，Luciferase reporter assay，Transfection and rifampicin induction，RNA isolation and real-time quantitative polymerase chain reaction (RT-qPCR) ，ChIP assay The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Immunohistochemical staining The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Plasmid construction，In vitro methylation，Luciferase reporter assay，Transfection and rifampicin induction，RNA isolation and real-time quantitative polymerase chain reaction (RT-qPCR) ，ChIP assay CYP3A4 The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. 29557377 chr1 156460952 156462952 MEF2D We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). human High+Lowthroughput A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts 否 T, B, NK cell E_01_0149 Gene array capture，Seq,Gene array capture We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). Immunohistochemical staining We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). Gene array capture，Seq,Gene array capture MEF2D We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). 29556082 chr11 65494664 65496664 MALAT1 MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. human High+Lowthroughput Transcriptional Profiling of Hypoxia-Regulated Non-coding RNAs in Human Primary Endothelial Cells 否 Primary endothelial cell E_01_0150 GRO-Seq and RNA-Seq, MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. Immunohistochemical staining MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. GRO-Seq and RNA-Seq, MALAT1 MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. 29554889 chr3 133743314 133745314 TF Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. human High+Lowthroughput Genomic analysis of transcriptional networks directing progression of cell states during MGE development. 否 E_01_0151 RT qPCR, in situ hybridization analysis, gene knockdown, chip SEQ, immunofluorescence staining Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. Immunohistochemical staining Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. RT-qPCR,原位杂交分析,基因敲降,ChIP-seq ,免疫荧光染色 TF,LHX6,LHX8 Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8.;Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8.;Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. 29549111 chr14 21495511 21497511 METTL3 The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. human High+Lowthroughput Disrupting the three-dimensional regulatory topology of the Pitx1 locus results in overtly normal development 否 Bone marrow stem cell E_01_0152 flow cytometry ，Real-time quantitative PCR ， staining ，Protein extraction ，Western blot ，Cell transfection ，Immunofluorescence assay ，Quantitative analysis ，Chromatin immunoprecipitation assay ，Luciferase reporter assay The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. Immunohistochemical staining The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. flow cytometry ，Real-time quantitative PCR ， staining ，Protein extraction ，Western blot ，Cell transfection ，Immunofluorescence assay ，Quantitative analysis ，Chromatin immunoprecipitation assay ，Luciferase reporter assay METTL3 The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. 29545900 chr2 226728889 226730889 IRS1 Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). human High+Lowthroughput Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis 否 HeLa cell E_01_0153 Nuclear magnetic resonance (NMR) spectroscopy analysis ，RNA extraction and real-time PCR ，Western blot analysis ，Histopathological analysis ,Analysis of glycated hemoglobin and β-cell function Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Immunohistochemical staining Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Nuclear magnetic resonance (NMR) spectroscopy analysis ，RNA extraction and real-time PCR ，Western blot analysis ，Histopathological analysis ,Analysis of glycated hemoglobin and β-cell function IRS1 Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). 29540468 chr17 66299977 66301977 PRKCA The PRKCA enhancer contains two common genetic variants and 4 haplotypes; human High+Lowthroughput Genetic Reduction in Left Ventricular Protein Kinase C-α and Adverse Ventricular Remodeling in Human Subjects 是 rs9912468 non-cardiac cell E_01_0154 PCR The PRKCA enhancer contains two common genetic variants and 4 haplotypes; Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The PRKCA enhancer contains two common genetic variants and 4 haplotypes; Immunohistochemical staining The PRKCA enhancer contains two common genetic variants and 4 haplotypes; PCR PRKCA The PRKCA enhancer contains two common genetic variants and 4 haplotypes; 29530320 chr3 181709448 181711448 SOX2 Epigenomic Profifiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma human lung High+Lowthroughput Synthetically Scalable Poly(ampholyte) Which Dramatically Enhances Cellular Cryopreservation 否 Lung squamous cell E_01_0155 Western blot, chip SEQ, RNA SEQ, flow cytometry, gene knockdown Epigenomic Profifiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Epigenomic Profifiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma Immunohistochemical staining Epigenomic Profifiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma Western blot,ChIP-seq,RNA-seq,流式细胞术,基因敲降 SOX2 Epigenomic Profifiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma 29526278 chr21 33540351 33542351 SON Four AONs and a sense oligonucleotide (SON) were designed to block exonic splicing enhancers (ESEs). human High+Lowthroughput Identification and Rescue of Splice Defects Caused by Two Neighboring Deep-Intronic ABCA4 Mutations Underlying Stargardt Disease 否 E_01_0156 RT-PCR Four AONs and a sense oligonucleotide (SON) were designed to block exonic splicing enhancers (ESEs). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Four AONs and a sense oligonucleotide (SON) were designed to block exonic splicing enhancers (ESEs). Immunohistochemical staining Four AONs and a sense oligonucleotide (SON) were designed to block exonic splicing enhancers (ESEs). RT-PCR SON Four AONs and a sense oligonucleotide (SON) were designed to block exonic splicing enhancers (ESEs). 29524130 chr14 21495467 21497467 METTL3 The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. human High+Lowthroughput Disrupting the three-dimensional regulatory topology of the Pitx1 locus results in overtly normal development 否 Bone marrow stem cell E_01_0157 flow cytometry ，Real-time quantitative PCR ， staining ，Protein extraction ，Western blot ，Cell transfection ，Immunofluorescence assay ，Quantitative analysis ，Chromatin immunoprecipitation assay ，Luciferase reporter assay The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. Immunohistochemical staining The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. flow cytometry ，Real-time quantitative PCR ， staining ，Protein extraction ，Western blot ，Cell transfection ，Immunofluorescence assay ，Quantitative analysis ，Chromatin immunoprecipitation assay ，Luciferase reporter assay METTL3 The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. 29523836 chr2 226728284 226730284 IRS1 Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). human High+Lowthroughput Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis 否 HeLa cell E_01_0158 Nuclear magnetic resonance (NMR) spectroscopy analysis ，RNA extraction and real-time PCR ，Western blot analysis ，Histopathological analysis ,Analysis of glycated hemoglobin and β-cell function Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Immunohistochemical staining Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Nuclear magnetic resonance (NMR) spectroscopy analysis ，RNA extraction and real-time PCR ，Western blot analysis ，Histopathological analysis ,Analysis of glycated hemoglobin and β-cell function IRS1 Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). 31223056 chr16 71843198 71845198 IST1 we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation human connective High+Lowthroughput MAPT/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-III complex formation: a vicious cycle in Alzheimer neurodegeneration 否 macrophage E_01_0159 PCR we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation Immunohistochemical staining we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation PCR IST1 we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation 31219650 chr7 44101654 44103654 AEBP1 In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. human Epithelial High+Lowthroughput AEBP1, a prognostic indicator, promotes colon adenocarcinoma cell growth and metastasis through the NF-κB pathway 否 colon cancer cell E_01_0160 PCR In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. Immunohistochemical staining In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. PCR AEBP1 In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. 31219209 chr7 148805028 148807028 EZH2 And lncRNA‐mediated epigenetic inhibition of antitumor gene via binding EZH2 in various cancers has been gradually detected. l human connective High+Lowthroughput Long noncoding RNA OIP5-AS1 aggravates cell proliferation, migration in gastric cancer by epigenetically silencing NLRP6 expression via binding EZH2 否 Colon cancer gastric cancer cell E_01_0161 PCR And lncRNA‐mediated epigenetic inhibition of antitumor gene via binding EZH2 in various cancers has been gradually detected. l Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq And lncRNA‐mediated epigenetic inhibition of antitumor gene via binding EZH2 in various cancers has been gradually detected. l Immunohistochemical staining And lncRNA‐mediated epigenetic inhibition of antitumor gene via binding EZH2 in various cancers has been gradually detected. l PCR EZH2 And lncRNA‐mediated epigenetic inhibition of antitumor gene via binding EZH2 in various cancers has been gradually detected. l 31216773 chr13 27958003 27960003 CDX2 It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco-2 cells. These results reveal a previously unknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for high expression levels in intestinal epithelial cells. human Colon High+Lowthroughput HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity 否 intestinal cell E_01_0162 PCR It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco-2 cells. These results reveal a previously unknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for high expression levels in intestinal epithelial cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco-2 cells. These results reveal a previously unknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for high expression levels in intestinal epithelial cells. Immunohistochemical staining It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco-2 cells. These results reveal a previously unknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for high expression levels in intestinal epithelial cells. PCR CDX2 It was found by chromatin immunoprecipitation experiments that CDX2 and HNF4α bind to the YAP1 enhancer in Caco-2 cells. These results reveal a previously unknown enhancer of the YAP1 promoter activity in the YAP1 gene, with importance for high expression levels in intestinal epithelial cells. 31216559 chr12 49973763 49975763 RACGAP1 Rac GTPase-activating protein 1 (RACGAP1) is as- sociated with cell proliferation, and there is much evidence of its oncogenic role. human connective High+Lowthroughput Rac GTPase-Activating Protein 1 (RACGAP1) as an Oncogenic Enhancer in Esophageal Carcinoma 否 cancer cell E_01_0163 PCR Rac GTPase-activating protein 1 (RACGAP1) is as- sociated with cell proliferation, and there is much evidence of its oncogenic role. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Rac GTPase-activating protein 1 (RACGAP1) is as- sociated with cell proliferation, and there is much evidence of its oncogenic role. Immunohistochemical staining Rac GTPase-activating protein 1 (RACGAP1) is as- sociated with cell proliferation, and there is much evidence of its oncogenic role. PCR RACGAP1 Rac GTPase-activating protein 1 (RACGAP1) is as- sociated with cell proliferation, and there is much evidence of its oncogenic role. 31216030 chr19 4171371 4173371 SIRT6 SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) re-sponsive genes during oxidative stress human connective High+Lowthroughput SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170 否 stem cell E_01_0164 PCR SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) re-sponsive genes during oxidative stress Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) re-sponsive genes during oxidative stress Immunohistochemical staining SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) re-sponsive genes during oxidative stress PCR SIRT6 SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) re-sponsive genes during oxidative stress 31215771 chr20 56626718 56628718 TFAP2C We found that the cooperations between regulators were much closer in lung‐metastatic cells. Moreover,regulators such as TFAP2C, GTF2I and LMO4 were found to have potential prognostic value for lung metastasis free (LMF) survival of breast cancer. human connective High+Lowthroughput Comprehensive epigenetic analyses reveal master regulators driving lung metastasis of breast cancer 否 mammary cancer breast cancer cell E_01_0165 PCR We found that the cooperations between regulators were much closer in lung‐metastatic cells. Moreover,regulators such as TFAP2C, GTF2I and LMO4 were found to have potential prognostic value for lung metastasis free (LMF) survival of breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that the cooperations between regulators were much closer in lung‐metastatic cells. Moreover,regulators such as TFAP2C, GTF2I and LMO4 were found to have potential prognostic value for lung metastasis free (LMF) survival of breast cancer. Immunohistochemical staining We found that the cooperations between regulators were much closer in lung‐metastatic cells. Moreover,regulators such as TFAP2C, GTF2I and LMO4 were found to have potential prognostic value for lung metastasis free (LMF) survival of breast cancer. PCR TFAP2C We found that the cooperations between regulators were much closer in lung‐metastatic cells. Moreover,regulators such as TFAP2C, GTF2I and LMO4 were found to have potential prognostic value for lung metastasis free (LMF) survival of breast cancer. 31213123 chr7 148804377 148806377 EZH2 Accumulating data demonstrated that Enhancer of zeste homolog 2 (EZH2) as an oncogenic pr otein is over-expressed in various human cancers, including PC. human connective High+Lowthroughput Diosgenin exhibits tumor suppressive function via down-regulation of EZH2 in pancreatic cancer cells 否 tumour tumor cell E_01_0166 PCR Accumulating data demonstrated that Enhancer of zeste homolog 2 (EZH2) as an oncogenic pr otein is over-expressed in various human cancers, including PC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Accumulating data demonstrated that Enhancer of zeste homolog 2 (EZH2) as an oncogenic pr otein is over-expressed in various human cancers, including PC. Immunohistochemical staining Accumulating data demonstrated that Enhancer of zeste homolog 2 (EZH2) as an oncogenic pr otein is over-expressed in various human cancers, including PC. PCR EZH2 Accumulating data demonstrated that Enhancer of zeste homolog 2 (EZH2) as an oncogenic pr otein is over-expressed in various human cancers, including PC. 31189106 chrX 137563628 137565628 ZIC3 Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation human connective High+Lowthroughput ZIC3 Controls the Transition from Naive to Primed Pluripotency 否 embryonic stem cell E_01_0167 PCR Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation Immunohistochemical staining Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation PCR ZIC3 Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation 31186776 chr1 205594870 205596870 ELK4 In addition, prognostic analysis demonstrated that ETV5 andELK4 expression levels were associated with the survival time of patients with GBM. These results suggested that ELK4 and ETV5 may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets. human connective High+Lowthroughput ceRNA network analysis reveals prognostic markers for glioblastoma 否 cancer cancer cell E_01_0168 PCR In addition, prognostic analysis demonstrated that ETV5 andELK4 expression levels were associated with the survival time of patients with GBM. These results suggested that ELK4 and ETV5 may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, prognostic analysis demonstrated that ETV5 andELK4 expression levels were associated with the survival time of patients with GBM. These results suggested that ELK4 and ETV5 may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets. Immunohistochemical staining In addition, prognostic analysis demonstrated that ETV5 andELK4 expression levels were associated with the survival time of patients with GBM. These results suggested that ELK4 and ETV5 may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets. PCR ELK4 In addition, prognostic analysis demonstrated that ETV5 andELK4 expression levels were associated with the survival time of patients with GBM. These results suggested that ELK4 and ETV5 may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets. 31186707 chr20 22578327 22580327 FOXA2 Long non-coding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) is a recently identified tumor suppressor in hepatocellular carcinoma. T human connective High+Lowthroughput Long non-coding RNA-neighboring enhancer of FOXA2 inhibits the migration and invasion of small cell lung carcinoma cells by downregulating transforming growth factor-β1 否 lung cancer Lung cancer cell E_01_0169 PCR Long non-coding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) is a recently identified tumor suppressor in hepatocellular carcinoma. T Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Long non-coding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) is a recently identified tumor suppressor in hepatocellular carcinoma. T Immunohistochemical staining Long non-coding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) is a recently identified tumor suppressor in hepatocellular carcinoma. T PCR FOXA2 Long non-coding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) is a recently identified tumor suppressor in hepatocellular carcinoma. T 31182783 chr6 31161443 31163443 POU5F1 OCT4, also named POU5F1, is the main regulator of pluripotency in stem cells1 It also has a part in tumorigenesis, cellular stress response, and hence is linked to various diseases from cancer to autoimmune disorders 2–4 .OCT4 possesses several isoforms with different functions at both protein and transcript levels, and their expressions are regulated through different mechanisms and at various biological processes 5,6 human connective High+Lowthroughput lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells 否 stem cell E_01_0170 PCR OCT4, also named POU5F1, is the main regulator of pluripotency in stem cells1 It also has a part in tumorigenesis, cellular stress response, and hence is linked to various diseases from cancer to autoimmune disorders 2–4 .OCT4 possesses several isoforms with different functions at both protein and transcript levels, and their expressions are regulated through different mechanisms and at various biological processes 5,6 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq OCT4, also named POU5F1, is the main regulator of pluripotency in stem cells1 It also has a part in tumorigenesis, cellular stress response, and hence is linked to various diseases from cancer to autoimmune disorders 2–4 .OCT4 possesses several isoforms with different functions at both protein and transcript levels, and their expressions are regulated through different mechanisms and at various biological processes 5,6 Immunohistochemical staining OCT4, also named POU5F1, is the main regulator of pluripotency in stem cells1 It also has a part in tumorigenesis, cellular stress response, and hence is linked to various diseases from cancer to autoimmune disorders 2–4 .OCT4 possesses several isoforms with different functions at both protein and transcript levels, and their expressions are regulated through different mechanisms and at various biological processes 5,6 PCR POU5F1 OCT4, also named POU5F1, is the main regulator of pluripotency in stem cells1 It also has a part in tumorigenesis, cellular stress response, and hence is linked to various diseases from cancer to autoimmune disorders 2–4 .OCT4 possesses several isoforms with different functions at both protein and transcript levels, and their expressions are regulated through different mechanisms and at various biological processes 5,6 31174563 chr11 65495199 65497199 MALAT1 Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. human connective High+Lowthroughput Long noncoding RNA MALAT1 potentiates growth and inhibits senescence by antagonizing ABI3BP in gallbladder cancer cells 否 Gallbladder cancer Gallbladder cancer cell E_01_0171 PCR Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. Immunohistochemical staining Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. PCR MALAT1 Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. 31171769 chr7 148803892 148805892 EZH2 We revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. human connective High+Lowthroughput Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma 否 Gliomas Glioma cell E_01_0172 PCR We revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. Immunohistochemical staining We revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. PCR EZH2 We revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. 31164150 chr16 67559426 67561426 CTCF Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genomeorganizer CTCF in the three dimensional chromatin space to regulate the transcription program important for the proper cell identity human epithelial cells High+Lowthroughput p63 cooperates with CTCF to modulate chromatin architecture in skin keratinocytes 否 glial cell E_01_0173 PCR Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genomeorganizer CTCF in the three dimensional chromatin space to regulate the transcription program important for the proper cell identity Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genomeorganizer CTCF in the three dimensional chromatin space to regulate the transcription program important for the proper cell identity Immunohistochemical staining Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genomeorganizer CTCF in the three dimensional chromatin space to regulate the transcription program important for the proper cell identity PCR CTCF Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genomeorganizer CTCF in the three dimensional chromatin space to regulate the transcription program important for the proper cell identity 31162630 chr7 148804276 148806276 EZH2 EZH2 inhibition might be a potential therapeutic target for restenosis. human Myotome High+Lowthroughput Inhibition of polycomb repressor complex 2 ameliorates neointimal hyperplasia by suppressing trimethylation of H3K27 in vascular smooth muscle cells 否 smooth muscle cell E_01_0174 PCR EZH2 inhibition might be a potential therapeutic target for restenosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 inhibition might be a potential therapeutic target for restenosis. Immunohistochemical staining EZH2 inhibition might be a potential therapeutic target for restenosis. PCR EZH2 EZH2 inhibition might be a potential therapeutic target for restenosis. 31160593 chr7 148804085 148806085 EZH2 We report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In a human connective High+Lowthroughput Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation 否 Colon cancer colon cancer cell E_01_0175 PCR We report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In a Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In a Immunohistochemical staining We report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In a PCR EZH2 We report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In a 31155838 chr11 69767717 69769717 FGF4 Data suggest that FGF-4 signalling is involved in EWS-Oct-4-mediated tumorigenesis, and that its inhibition impairs tumour growth in vivo significantly human connective High+Lowthroughput Critical role of the fibroblast growth factor signalling pathway in Ewing's sarcoma octamer-binding transcription factor 4-mediated cell proliferation and tumorigenesis 否 tumour tumor cell E_01_0176 PCR Data suggest that FGF-4 signalling is involved in EWS-Oct-4-mediated tumorigenesis, and that its inhibition impairs tumour growth in vivo significantly Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Data suggest that FGF-4 signalling is involved in EWS-Oct-4-mediated tumorigenesis, and that its inhibition impairs tumour growth in vivo significantly Immunohistochemical staining Data suggest that FGF-4 signalling is involved in EWS-Oct-4-mediated tumorigenesis, and that its inhibition impairs tumour growth in vivo significantly PCR FGF4 Data suggest that FGF-4 signalling is involved in EWS-Oct-4-mediated tumorigenesis, and that its inhibition impairs tumour growth in vivo significantly 31081034 chr18 55219304 55221304 TCF4 The psychiatric risk-associated transcription factor 4 (TCF4) is linked to schizophrenia. Rare TCF4 coding variants are found in individuals with PittHopkins syndrome an intellectual disability and autism spectrum disorder. human connective High+Lowthroughput Structural basis for preferential binding of human TCF4 to DNA containing 5-carboxylcytosine 否 neural cell E_01_0177 PCR The psychiatric risk-associated transcription factor 4 (TCF4) is linked to schizophrenia. Rare TCF4 coding variants are found in individuals with PittHopkins syndrome an intellectual disability and autism spectrum disorder. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The psychiatric risk-associated transcription factor 4 (TCF4) is linked to schizophrenia. Rare TCF4 coding variants are found in individuals with PittHopkins syndrome an intellectual disability and autism spectrum disorder. Immunohistochemical staining The psychiatric risk-associated transcription factor 4 (TCF4) is linked to schizophrenia. Rare TCF4 coding variants are found in individuals with PittHopkins syndrome an intellectual disability and autism spectrum disorder. PCR TCF4 The psychiatric risk-associated transcription factor 4 (TCF4) is linked to schizophrenia. Rare TCF4 coding variants are found in individuals with PittHopkins syndrome an intellectual disability and autism spectrum disorder. 30995827 chr20 22578226 22580226 FOXA2 The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). human connective High+Lowthroughput Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (SLC25A13): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells 否 cancer cell E_01_0178 PCR The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). Immunohistochemical staining The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). PCR FOXA2 The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). 31127282 chr16 67559749 67561749 CTCF CTCF is an important regulator of the 3D chromatin ar- chitecture of interphase chromosomes, which guides gene expression (10–13). human connective High+Lowthroughput Acute depletion of CTCF directly affects MYC regulation through loss of enhancer-promoter looping 否 E_01_0179 PCR CTCF is an important regulator of the 3D chromatin ar- chitecture of interphase chromosomes, which guides gene expression (10–13). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CTCF is an important regulator of the 3D chromatin ar- chitecture of interphase chromosomes, which guides gene expression (10–13). Immunohistochemical staining CTCF is an important regulator of the 3D chromatin ar- chitecture of interphase chromosomes, which guides gene expression (10–13). PCR CTCF CTCF is an important regulator of the 3D chromatin ar- chitecture of interphase chromosomes, which guides gene expression (10–13). 31053723 chr11 2126891 2128891 IGF2 This work suggests a mechanism for epigenetic regulation of dopamine levels in the brain. Epigenetic misregulation of an enhancer at IGF2 may underlie the dopaminergic abnormalities that drives psychotic symptoms. human connective High+Lowthroughput Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosis 是 neural cell E_01_0180 PCR This work suggests a mechanism for epigenetic regulation of dopamine levels in the brain. Epigenetic misregulation of an enhancer at IGF2 may underlie the dopaminergic abnormalities that drives psychotic symptoms. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This work suggests a mechanism for epigenetic regulation of dopamine levels in the brain. Epigenetic misregulation of an enhancer at IGF2 may underlie the dopaminergic abnormalities that drives psychotic symptoms. Immunohistochemical staining This work suggests a mechanism for epigenetic regulation of dopamine levels in the brain. Epigenetic misregulation of an enhancer at IGF2 may underlie the dopaminergic abnormalities that drives psychotic symptoms. PCR IGF2 This work suggests a mechanism for epigenetic regulation of dopamine levels in the brain. Epigenetic misregulation of an enhancer at IGF2 may underlie the dopaminergic abnormalities that drives psychotic symptoms. 31053176 chrX 153441659 153443659 TREX2 The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. human connective High+Lowthroughput DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer 是 laryngeal carcinoma cell E_01_0181 PCR The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Immunohistochemical staining The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. PCR TREX2 The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. 31721105 chr12 117450290 117452290 KSR2 In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. human liver High+Lowthroughput Expression analysis of LTR-derived miR-1269a and target gene, KSR2 in Sebastes schlegelii 否 liver cancer HCC cell E_01_0182 In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. Immunohistochemical staining In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. KSR2 In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. 31718595 chr7 148804304 148806304 EZH2 Overexpression of EZH2 is positively correlated with tissue pathological grade and stage,metastasis, and poor survival in many types of solid tumors, including lung cancer, breast cancer, gastric cancer, prostate cancer, and melanoma. human connective High+Lowthroughput EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma 否 cancer Cancer Stem Cell E_01_0183 PCR, Western blot, immunofluorescence staining Overexpression of EZH2 is positively correlated with tissue pathological grade and stage,metastasis, and poor survival in many types of solid tumors, including lung cancer, breast cancer, gastric cancer, prostate cancer, and melanoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overexpression of EZH2 is positively correlated with tissue pathological grade and stage,metastasis, and poor survival in many types of solid tumors, including lung cancer, breast cancer, gastric cancer, prostate cancer, and melanoma. Immunohistochemical staining Overexpression of EZH2 is positively correlated with tissue pathological grade and stage,metastasis, and poor survival in many types of solid tumors, including lung cancer, breast cancer, gastric cancer, prostate cancer, and melanoma. PCR、Western blot、免疫荧光染色 EZH2 Overexpression of EZH2 is positively correlated with tissue pathological grade and stage,metastasis, and poor survival in many types of solid tumors, including lung cancer, breast cancer, gastric cancer, prostate cancer, and melanoma. 31698100 chr20 13993019 13995019 MACROD2 Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. human High+Lowthroughput Split hand/foot malformation associated with 20p12.1 deletion: A case report 是 Split hand / foot malformation E_01_0184 PCR Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. Immunohistochemical staining Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. PCR MACROD2,KIF16B Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. ;Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. 31694013 chr7 148804620 148806620 EZH2 Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities human intestines High+Lowthroughput Oleanolic Acid Acetate Exerts Anti-Inflammatory Activity via IKKα/β Suppression in TLR3-Mediated NF-κB Activation 否 Colon cancer colon cancer cell E_01_0185 PCR Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities PCR EZH2 Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities 31693890 chr7 148804304 148806304 EZH2 The histone methyl transferase enhancer of zeste ho_x0002_molog 2 (EZH2) is a master transcriptional regulatorinvolved in histone H3 lysine 27 trimethylation. human breast High+Lowthroughput Enhancer of Zeste Homolog 2 in Colorectal Cancer Development and Progression 否 mammary cancer breast cancer cell E_01_0186 PCR,Western blot,Flow cytometry The histone methyl transferase enhancer of zeste ho_x0002_molog 2 (EZH2) is a master transcriptional regulatorinvolved in histone H3 lysine 27 trimethylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The histone methyl transferase enhancer of zeste ho_x0002_molog 2 (EZH2) is a master transcriptional regulatorinvolved in histone H3 lysine 27 trimethylation. Immunohistochemical staining The histone methyl transferase enhancer of zeste ho_x0002_molog 2 (EZH2) is a master transcriptional regulatorinvolved in histone H3 lysine 27 trimethylation. PCR,Western blot,Flow cytometry EZH2 The histone methyl transferase enhancer of zeste ho_x0002_molog 2 (EZH2) is a master transcriptional regulatorinvolved in histone H3 lysine 27 trimethylation. 31693439 chr15 90963083 90965083 PRC1 Four are the main epigenetic pathways involved in this kind of networks and considered in our analysis. The polycomb-repressive complex 1 (PRC1), a transcriptional-repressor complex consisting of several proteins among which an important role is played by the Polycomb group ring finger ones (in particular Bmi-1) and whose action is responsible of the ubiquitylation of H2AK119ub1 human bone marrow High+Lowthroughput Regulation of EZH2 by SMYD2-Mediated Lysine Methylation Is Implicated in Tumorigenesis 否 Myeloma Myeloma cell E_01_0187 PCR,Western blot,Flow cytometry Four are the main epigenetic pathways involved in this kind of networks and considered in our analysis. The polycomb-repressive complex 1 (PRC1), a transcriptional-repressor complex consisting of several proteins among which an important role is played by the Polycomb group ring finger ones (in particular Bmi-1) and whose action is responsible of the ubiquitylation of H2AK119ub1 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Four are the main epigenetic pathways involved in this kind of networks and considered in our analysis. The polycomb-repressive complex 1 (PRC1), a transcriptional-repressor complex consisting of several proteins among which an important role is played by the Polycomb group ring finger ones (in particular Bmi-1) and whose action is responsible of the ubiquitylation of H2AK119ub1 Immunohistochemical staining Four are the main epigenetic pathways involved in this kind of networks and considered in our analysis. The polycomb-repressive complex 1 (PRC1), a transcriptional-repressor complex consisting of several proteins among which an important role is played by the Polycomb group ring finger ones (in particular Bmi-1) and whose action is responsible of the ubiquitylation of H2AK119ub1 PCR,Western blot,Flow cytometry PRC1 Four are the main epigenetic pathways involved in this kind of networks and considered in our analysis. The polycomb-repressive complex 1 (PRC1), a transcriptional-repressor complex consisting of several proteins among which an important role is played by the Polycomb group ring finger ones (in particular Bmi-1) and whose action is responsible of the ubiquitylation of H2AK119ub1 31690584 chr17 72118178 72120178 SOX9 Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase human breast High+Lowthroughput The hTERT-VNTR2-2(nd) alleles are involved in genomic stability in gastrointestinal cancer 否 mammary cancer breast cancer cell E_01_0188 PCR, Western blot, gene knockdown Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase Immunohistochemical staining Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase PCR,Western blot,基因敲降 SOX9 Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase 31682213 chr20 44582166 44584166 ADA Azodicarbonamide (ADA) is a dough-enhancer, which in Nigeria is an approved replacement for potassium bromate (a dough-enhancer that has been banned in a number of coun_x0002_tries due to its nephrotoxic potential). human connective High+Lowthroughput An Assessment of the Effects of Azodicarbonamide-containing Diet on Neurobehaviour, Brain Antioxidant Status and Membrane Lipid Peroxidation Status in Rats 否 E_01_0189 PCR Azodicarbonamide (ADA) is a dough-enhancer, which in Nigeria is an approved replacement for potassium bromate (a dough-enhancer that has been banned in a number of coun_x0002_tries due to its nephrotoxic potential). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Azodicarbonamide (ADA) is a dough-enhancer, which in Nigeria is an approved replacement for potassium bromate (a dough-enhancer that has been banned in a number of coun_x0002_tries due to its nephrotoxic potential). Immunohistochemical staining Azodicarbonamide (ADA) is a dough-enhancer, which in Nigeria is an approved replacement for potassium bromate (a dough-enhancer that has been banned in a number of coun_x0002_tries due to its nephrotoxic potential). PCR ADA Azodicarbonamide (ADA) is a dough-enhancer, which in Nigeria is an approved replacement for potassium bromate (a dough-enhancer that has been banned in a number of coun_x0002_tries due to its nephrotoxic potential). 31680128 chr11 1155000 1157000 MUC5AC MUC5AC and MUC5B is a major gel-forming mucin that is linked to increased morbidity and mortality in respiratory diseases human Epithelial High+Lowthroughput Fipronil upregulates inflammatory cytokines and MUC5AC expression in human nasal epithelial cells 否 airway inflammation epithelial cell E_01_0190 Western blot,PCR MUC5AC and MUC5B is a major gel-forming mucin that is linked to increased morbidity and mortality in respiratory diseases Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MUC5AC and MUC5B is a major gel-forming mucin that is linked to increased morbidity and mortality in respiratory diseases Immunohistochemical staining MUC5AC and MUC5B is a major gel-forming mucin that is linked to increased morbidity and mortality in respiratory diseases Western blot,PCR MUC5AC MUC5AC and MUC5B is a major gel-forming mucin that is linked to increased morbidity and mortality in respiratory diseases 31676868 chr20 40683274 40685274 MAFB Thus, we took advantage of published ChIP_x0002_seq datasets of islet-specific transcription factors (MAFB, PDX1, FOXA2, NKX6.1 and NKX2.2) mapped in unstimulated human pancreatic islets9 to measure transcription factor occupancy in primed and neo-enhancers before the proinflammatory stimu_x0002_lus. human blood High+Lowthroughput The impact of proinflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes 是 rs78037977 diabetes B cell E_01_0191 Flow cytometry,PCR Thus, we took advantage of published ChIP_x0002_seq datasets of islet-specific transcription factors (MAFB, PDX1, FOXA2, NKX6.1 and NKX2.2) mapped in unstimulated human pancreatic islets9 to measure transcription factor occupancy in primed and neo-enhancers before the proinflammatory stimu_x0002_lus. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, we took advantage of published ChIP_x0002_seq datasets of islet-specific transcription factors (MAFB, PDX1, FOXA2, NKX6.1 and NKX2.2) mapped in unstimulated human pancreatic islets9 to measure transcription factor occupancy in primed and neo-enhancers before the proinflammatory stimu_x0002_lus. Immunohistochemical staining Thus, we took advantage of published ChIP_x0002_seq datasets of islet-specific transcription factors (MAFB, PDX1, FOXA2, NKX6.1 and NKX2.2) mapped in unstimulated human pancreatic islets9 to measure transcription factor occupancy in primed and neo-enhancers before the proinflammatory stimu_x0002_lus. Flow cytometry,PCR DEXI MAFB,SOCS1 The locus includes several upregulated genes (SOCS1, DEXI, CIITA, RMI2) that could represent potential targets of this IRE. Recent research points to DEXI as a T1D candidate gene in immune cells and β cells31,32. Thus, we took advantage of published ChIP_x0002_seq datasets of islet-specific transcription factors (MAFB, PDX1, FOXA2, NKX6.1 and NKX2.2) mapped in unstimulated human pancreatic islets9 to measure transcription factor occupancy in primed and neo-enhancers before the proinflammatory stimu_x0002_lus.;The locus includes several upregulated genes (SOCS1, DEXI, CIITA, RMI2) that could represent potential targets of this IRE. Recent research points to DEXI as a T1D candidate gene in immune cells and β cells31,32. 31666694 chr11 69983276 69985276 ANO1 By contrast, ANO1 was bi-allelically expressed, suggesting that the biased FGF expression reflected allele_x0002_specific insulator loss. Consistently, in one SDH-deficient tumour with a heterozygous SNP near the CTCF site, we confirmed that only one allele of the FGF insulator was methylated (Extended Data Fig. 4d). human Stomach, gut High+Lowthroughput Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs 否 Gastrointestinal stromal tumors GIST-T1 cell E_01_0192 Flow cytometry By contrast, ANO1 was bi-allelically expressed, suggesting that the biased FGF expression reflected allele_x0002_specific insulator loss. Consistently, in one SDH-deficient tumour with a heterozygous SNP near the CTCF site, we confirmed that only one allele of the FGF insulator was methylated (Extended Data Fig. 4d). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By contrast, ANO1 was bi-allelically expressed, suggesting that the biased FGF expression reflected allele_x0002_specific insulator loss. Consistently, in one SDH-deficient tumour with a heterozygous SNP near the CTCF site, we confirmed that only one allele of the FGF insulator was methylated (Extended Data Fig. 4d). Immunohistochemical staining By contrast, ANO1 was bi-allelically expressed, suggesting that the biased FGF expression reflected allele_x0002_specific insulator loss. Consistently, in one SDH-deficient tumour with a heterozygous SNP near the CTCF site, we confirmed that only one allele of the FGF insulator was methylated (Extended Data Fig. 4d). Flow cytometry ANO1 By contrast, ANO1 was bi-allelically expressed, suggesting that the biased FGF expression reflected allele_x0002_specific insulator loss. Consistently, in one SDH-deficient tumour with a heterozygous SNP near the CTCF site, we confirmed that only one allele of the FGF insulator was methylated (Extended Data Fig. 4d). 31666072 chr17 50181276 50183276 COL1A1 Many mutations associated with these conditions (e.g., col_x0002_lagen [COL1A1] in patients with Ehlers-Danlos syndrome)affect the structural integrity of the vasculature or the abil_x0002_ity of the vessel walls to maintain homeostasis [12, 13]. human Epithelial High+Lowthroughput Epigenetic landscapes suggest that genetic risk for intracranial aneurysm operates on the endothelium 是 rs1333040 inflammation endothelial cell E_01_0193 ChIP-Seq Many mutations associated with these conditions (e.g., col_x0002_lagen [COL1A1] in patients with Ehlers-Danlos syndrome)affect the structural integrity of the vasculature or the abil_x0002_ity of the vessel walls to maintain homeostasis [12, 13]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Many mutations associated with these conditions (e.g., col_x0002_lagen [COL1A1] in patients with Ehlers-Danlos syndrome)affect the structural integrity of the vasculature or the abil_x0002_ity of the vessel walls to maintain homeostasis [12, 13]. Immunohistochemical staining Many mutations associated with these conditions (e.g., col_x0002_lagen [COL1A1] in patients with Ehlers-Danlos syndrome)affect the structural integrity of the vasculature or the abil_x0002_ity of the vessel walls to maintain homeostasis [12, 13]. ChIP-Seq COL1A1 Many mutations associated with these conditions (e.g., col_x0002_lagen [COL1A1] in patients with Ehlers-Danlos syndrome)affect the structural integrity of the vasculature or the abil_x0002_ity of the vessel walls to maintain homeostasis [12, 13]. 31665067 chr18 55219450 55221450 TCF4 While pro_x0002_moting the transcription of tumor suppressors genes,RUVBL1 was revealed to promote β-catenin-mediated neoplastic transformation by forming chromatin remod_x0002_eling complex with TIP60 and thus promotes histone H4 acetylation in the promoter region of ITF-2 gene and enhances the transcriptional activity of TCF4 [42]. human bone High+Lowthroughput CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to enhance the transcriptional activity of β-catenin/LEF1 complex via effects on chromatin remodeling 否 Osteosarcoma osteosarcoma cell E_01_0194 Flow cytometry,PCR,Western blot While pro_x0002_moting the transcription of tumor suppressors genes,RUVBL1 was revealed to promote β-catenin-mediated neoplastic transformation by forming chromatin remod_x0002_eling complex with TIP60 and thus promotes histone H4 acetylation in the promoter region of ITF-2 gene and enhances the transcriptional activity of TCF4 [42]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq While pro_x0002_moting the transcription of tumor suppressors genes,RUVBL1 was revealed to promote β-catenin-mediated neoplastic transformation by forming chromatin remod_x0002_eling complex with TIP60 and thus promotes histone H4 acetylation in the promoter region of ITF-2 gene and enhances the transcriptional activity of TCF4 [42]. Immunohistochemical staining While pro_x0002_moting the transcription of tumor suppressors genes,RUVBL1 was revealed to promote β-catenin-mediated neoplastic transformation by forming chromatin remod_x0002_eling complex with TIP60 and thus promotes histone H4 acetylation in the promoter region of ITF-2 gene and enhances the transcriptional activity of TCF4 [42]. Flow cytometry,PCR,Western blot MYO10 TCF4 In this study, we identified the oncogenic role of cir_x0002_cMYO10, a circRNA that is upregulated in OS [44]. While pro_x0002_moting the transcription of tumor suppressors genes,RUVBL1 was revealed to promote β-catenin-mediated neoplastic transformation by forming chromatin remod_x0002_eling complex with TIP60 and thus promotes histone H4 acetylation in the promoter region of ITF-2 gene and enhances the transcriptional activity of TCF4 [42]. 31664109 chrX 154007840 154009840 IRAK1 IRAK1, IRAK2 and IRAK4 work in concert to stimulate myeloid diferentiation primary response 88 (MyD88) dependent activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and thus pro-infammatory cytokine production12. human blood High+Lowthroughput IRAK3 modulates downstream innate immune signalling through its guanylate cyclase activity 是 inflammation B cell E_01_0195 PCR IRAK1, IRAK2 and IRAK4 work in concert to stimulate myeloid diferentiation primary response 88 (MyD88) dependent activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and thus pro-infammatory cytokine production12. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq IRAK1, IRAK2 and IRAK4 work in concert to stimulate myeloid diferentiation primary response 88 (MyD88) dependent activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and thus pro-infammatory cytokine production12. Immunohistochemical staining IRAK1, IRAK2 and IRAK4 work in concert to stimulate myeloid diferentiation primary response 88 (MyD88) dependent activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and thus pro-infammatory cytokine production12. PCR IRAK1,IRAK4 IRAK1, IRAK2 and IRAK4 work in concert to stimulate myeloid diferentiation primary response 88 (MyD88) dependent activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and thus pro-infammatory cytokine production12. ;IRAK1, IRAK2 and IRAK4 work in concert to stimulate myeloid diferentiation primary response 88 (MyD88) dependent activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) and thus pro-infammatory cytokine production12. 31659808 chr2 237482764 237484764 MLPH To determine the potential effect of rs13426236 genotypes on MLPH alternative splicing, we performed splicing variant‐specific qPCRs in 87 benign prostate tissues. human prostate High+Lowthroughput Single-nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4 是 rs13426236 prostatic cancer prostate cancer cell E_01_0196 Flow cytometry,Western blot,PCR To determine the potential effect of rs13426236 genotypes on MLPH alternative splicing, we performed splicing variant‐specific qPCRs in 87 benign prostate tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To determine the potential effect of rs13426236 genotypes on MLPH alternative splicing, we performed splicing variant‐specific qPCRs in 87 benign prostate tissues. Immunohistochemical staining To determine the potential effect of rs13426236 genotypes on MLPH alternative splicing, we performed splicing variant‐specific qPCRs in 87 benign prostate tissues. Flow cytometry,Western blot,PCR MLPH To determine the potential effect of rs13426236 genotypes on MLPH alternative splicing, we performed splicing variant‐specific qPCRs in 87 benign prostate tissues. 31659207 chr11 128455802 128457802 ETS1 ETS1 is involved in B cell and T17 cell diferentiation, and an association between rs1128334 and SLE has been reported in Asian SLE cohorts39. human blood High+Lowthroughput Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus 是 rs9888739 Systemic lupus erythematosus T cell E_01_0197 Flow cytometry,PCR ETS1 is involved in B cell and T17 cell diferentiation, and an association between rs1128334 and SLE has been reported in Asian SLE cohorts39. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ETS1 is involved in B cell and T17 cell diferentiation, and an association between rs1128334 and SLE has been reported in Asian SLE cohorts39. Immunohistochemical staining ETS1 is involved in B cell and T17 cell diferentiation, and an association between rs1128334 and SLE has been reported in Asian SLE cohorts39. Flow cytometry,PCR TLR7,TNPO3 ETS1,FOXP3,TNIP1,IRF5 Moreover, mice lacking Gf1 have recently been reported to develop a TLR7-dependent lupus-like phenotype, which the authors showed to involve excess NFκB signaling45.;The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. ETS1 is involved in B cell and T17 cell diferentiation, and an association between rs1128334 and SLE has been reported in Asian SLE cohorts39.;Te rare variant we identifed at this locus was located in a lower information nucleotide in a FOXP3 motif and was found to increase ETS1 expression via luciferase assay (Fig. 1D and Supplementary Table 1).;We found a rare variant near rs10036748, within the TNIP1 gene, which impaired TNIP1 expression according to a luciferase reporter assay (Fig. 1E and Supplementary Table 1).;We identifed novel variants in the loci of IRF5, ETS1, ITGAM1 and TNIP1, each of which caused alterations in the expression levels of the association genes. 31659164 chr8 11673920 11675920 GATA4 Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. human connective High+Lowthroughput A reference map of murine cardiac transcription factor chromatin occupancy identifies dynamic and conserved enhancers 否 cancer stem cell E_01_0198 PCR,Flow cytometry Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. Immunohistochemical staining Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. PCR,Flow cytometry GATA4,NKX2-5,MEF2A Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. ;The development of the heart is orchestrated by intricate transcriptional programs, so that mutations in TFs and epigenetic regulators are important causes of congenital heart disease5. Among the well known cardiac TFs are NKX2-5, TBX5, GATA4,MEF2A, MEF2C, and SRF6–11. ;The development of the heart is orchestrated by intricate transcriptional programs, so that mutations in TFs and epigenetic regulators are important causes of congenital heart disease5. Among the well known cardiac TFs are NKX2-5, TBX5, GATA4,MEF2A, MEF2C, and SRF6–11. 31652453 chr7 148804156 148806156 EZH2 FBP1 expression in tumor cells is linked to poor patient survival.27,32 Recently, we demonstrated that FBP1 physically interacted with EZH2 in osteosarcoma cells and that GSK343 treatment inhibited the expression of EZH2 and FBP1.23 human bone High+Lowthroughput Ketamine induces endoplasmic reticulum stress in rats and SV-HUC-1 human uroepithelial cells by activating NLRP3/TXNIP aix 否 Osteosarcoma osteosarcoma cell E_01_0199 Flow cytometry, Western blot, PCR, immunofluorescence light staining FBP1 expression in tumor cells is linked to poor patient survival.27,32 Recently, we demonstrated that FBP1 physically interacted with EZH2 in osteosarcoma cells and that GSK343 treatment inhibited the expression of EZH2 and FBP1.23 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FBP1 expression in tumor cells is linked to poor patient survival.27,32 Recently, we demonstrated that FBP1 physically interacted with EZH2 in osteosarcoma cells and that GSK343 treatment inhibited the expression of EZH2 and FBP1.23 Immunohistochemical staining FBP1 expression in tumor cells is linked to poor patient survival.27,32 Recently, we demonstrated that FBP1 physically interacted with EZH2 in osteosarcoma cells and that GSK343 treatment inhibited the expression of EZH2 and FBP1.23 Flow cytometry,Western blot,PCR,免疫荧光光染色 FBP1 EZH2 FBP1 expression in tumor cells is linked to poor patient survival.27,32 Recently, we demonstrated that FBP1 physically interacted with EZH2 in osteosarcoma cells and that GSK343 treatment inhibited the expression of EZH2 and FBP1.23 FBP1 expression in tumor cells is linked to poor patient survival.27,32 Recently, we demonstrated that FBP1 physically interacted with EZH2 in osteosarcoma cells and that GSK343 treatment inhibited the expression of EZH2 and FBP1.23 31649059 chr1 8001795 8003795 ERRFI1 As exemplified by the ERRFI1 locus (Fig.3A) and summarized genome-wide for all TSSs (Fig. 3B), both transient and stable transcript TSSs are accurately captured by csRNA-seq. human blood High+Lowthroughput Identification and dynamic quantification of regulatory elements using total RNA 否 leukemia myelogenous leukemia cell E_01_0200 Flow cytometry As exemplified by the ERRFI1 locus (Fig.3A) and summarized genome-wide for all TSSs (Fig. 3B), both transient and stable transcript TSSs are accurately captured by csRNA-seq. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As exemplified by the ERRFI1 locus (Fig.3A) and summarized genome-wide for all TSSs (Fig. 3B), both transient and stable transcript TSSs are accurately captured by csRNA-seq. Immunohistochemical staining As exemplified by the ERRFI1 locus (Fig.3A) and summarized genome-wide for all TSSs (Fig. 3B), both transient and stable transcript TSSs are accurately captured by csRNA-seq. Flow cytometry ERRFI1 As exemplified by the ERRFI1 locus (Fig.3A) and summarized genome-wide for all TSSs (Fig. 3B), both transient and stable transcript TSSs are accurately captured by csRNA-seq. 31649055 chr2 47342302 47344302 EPCAM The significantly differentially expressed genes include common clinical biomarkers for macrophages (CD68 and CD163) and DCIS cells (EPCAM, KRT7, KRT18, and ERBB2 [also known as HER2]) (Fig. 4C; Supplemental File 3). The single-cell samples generally have gene expression profiles similar to the cell type–matched bulk samples. human connective High+Lowthroughput FFPEcap-seq: a method for sequencing capped RNAs in formalin-fixed paraffin-embedded samples 是 leukemia stromal macrophage cell E_01_0201 Flow cytometry The significantly differentially expressed genes include common clinical biomarkers for macrophages (CD68 and CD163) and DCIS cells (EPCAM, KRT7, KRT18, and ERBB2 [also known as HER2]) (Fig. 4C; Supplemental File 3). The single-cell samples generally have gene expression profiles similar to the cell type–matched bulk samples. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The significantly differentially expressed genes include common clinical biomarkers for macrophages (CD68 and CD163) and DCIS cells (EPCAM, KRT7, KRT18, and ERBB2 [also known as HER2]) (Fig. 4C; Supplemental File 3). The single-cell samples generally have gene expression profiles similar to the cell type–matched bulk samples. Immunohistochemical staining The significantly differentially expressed genes include common clinical biomarkers for macrophages (CD68 and CD163) and DCIS cells (EPCAM, KRT7, KRT18, and ERBB2 [also known as HER2]) (Fig. 4C; Supplemental File 3). The single-cell samples generally have gene expression profiles similar to the cell type–matched bulk samples. Flow cytometry EPCAM The significantly differentially expressed genes include common clinical biomarkers for macrophages (CD68 and CD163) and DCIS cells (EPCAM, KRT7, KRT18, and ERBB2 [also known as HER2]) (Fig. 4C; Supplemental File 3). The single-cell samples generally have gene expression profiles similar to the cell type–matched bulk samples. 31649032 chr3 66876146 66878146 Shox2 Using mice, here we report that deficiency in short stature homeobox 2 (Shox2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla, but does not affect the palatine. mouse connective High+Lowthroughput Shox2 regulates osteogenic differentiation and pattern formation during hard palate development in mice 否 mesenchymal cell E_01_0202 Flow cytometry, PCR, immunofluorescence staining Using mice, here we report that deficiency in short stature homeobox 2 (Shox2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla, but does not affect the palatine. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using mice, here we report that deficiency in short stature homeobox 2 (Shox2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla, but does not affect the palatine. Immunohistochemical staining Using mice, here we report that deficiency in short stature homeobox 2 (Shox2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla, but does not affect the palatine. Flow cytometry,PCR,免疫荧光染色 Shox2 Using mice, here we report that deficiency in short stature homeobox 2 (Shox2), a transcriptional regulator whose expression is restricted to the anterior palatal mesenchyme, leads to a defective palatine process of the maxilla, but does not affect the palatine. 31644352 chr16 28929347 28931347 CD19 Wounds were digested as described above. Single cell suspen_x0002_sions were incubated with fluorescein isothiocyanate–labeled anti-CD3, anti-CD19, and anti-Ly6G (BioLegend) followed by antifluorescein isothiocyanate microbeads (Miltenyi Biotec). human blood High+Lowthroughput Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing 否 septicemia B cell E_01_0203 PCR, flow cytometry, immunofluorescence staining Wounds were digested as described above. Single cell suspen_x0002_sions were incubated with fluorescein isothiocyanate–labeled anti-CD3, anti-CD19, and anti-Ly6G (BioLegend) followed by antifluorescein isothiocyanate microbeads (Miltenyi Biotec). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Wounds were digested as described above. Single cell suspen_x0002_sions were incubated with fluorescein isothiocyanate–labeled anti-CD3, anti-CD19, and anti-Ly6G (BioLegend) followed by antifluorescein isothiocyanate microbeads (Miltenyi Biotec). Immunohistochemical staining Wounds were digested as described above. Single cell suspen_x0002_sions were incubated with fluorescein isothiocyanate–labeled anti-CD3, anti-CD19, and anti-Ly6G (BioLegend) followed by antifluorescein isothiocyanate microbeads (Miltenyi Biotec). PCR,Flow cytometry,免疫荧光染色 CD19 Wounds were digested as described above. Single cell suspen_x0002_sions were incubated with fluorescein isothiocyanate–labeled anti-CD3, anti-CD19, and anti-Ly6G (BioLegend) followed by antifluorescein isothiocyanate microbeads (Miltenyi Biotec). 31642979 chr4 184382613 184384613 IRF2 Similarly, IRF2 was predicted to bind to the sequence with the T allele at rs7071351 (Fig. 3d) and IRF2 ChIP-seq peak was also found in the SNP region (Fig. 3b). human colon High+Lowthroughput Three functional variants were identified to affect RPS24 expression and significantly associated with risk of colorectal cancer 是 rs7071351 Colon cancer Human colorectal carcinoma cell E_01_0204 PCR,Flow cytometry Similarly, IRF2 was predicted to bind to the sequence with the T allele at rs7071351 (Fig. 3d) and IRF2 ChIP-seq peak was also found in the SNP region (Fig. 3b). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Similarly, IRF2 was predicted to bind to the sequence with the T allele at rs7071351 (Fig. 3d) and IRF2 ChIP-seq peak was also found in the SNP region (Fig. 3b). Immunohistochemical staining Similarly, IRF2 was predicted to bind to the sequence with the T allele at rs7071351 (Fig. 3d) and IRF2 ChIP-seq peak was also found in the SNP region (Fig. 3b). PCR,Flow cytometry IRF2,ZMIZ1 Similarly, IRF2 was predicted to bind to the sequence with the T allele at rs7071351 (Fig. 3d) and IRF2 ChIP-seq peak was also found in the SNP region (Fig. 3b).;However, ZMIZ1-AS1 is a miscellaneous RNA gene with unknown function and both ZMIZ1 and ZMIZ1-AS1 failed to afect cell growth in our functionalinterrogation. 31642363 chr7 148804489 148806489 EZH2 Enhancer of zeste homolog 2 (EZH2), a catalytic component of the polycomb repressive complex 2, acts as a methyltrans_x0002_ferase for H3 lysine 27 trimethylation, mod_x0002_ulates chromatin structure and gene expression, and recruits DNA methyltrans_x0002_ferases for gene silencing.2 human connective High+Lowthroughput Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing 否 mesenchymal stem cell E_01_0205 PCR,Western blot Enhancer of zeste homolog 2 (EZH2), a catalytic component of the polycomb repressive complex 2, acts as a methyltrans_x0002_ferase for H3 lysine 27 trimethylation, mod_x0002_ulates chromatin structure and gene expression, and recruits DNA methyltrans_x0002_ferases for gene silencing.2 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2), a catalytic component of the polycomb repressive complex 2, acts as a methyltrans_x0002_ferase for H3 lysine 27 trimethylation, mod_x0002_ulates chromatin structure and gene expression, and recruits DNA methyltrans_x0002_ferases for gene silencing.2 Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2), a catalytic component of the polycomb repressive complex 2, acts as a methyltrans_x0002_ferase for H3 lysine 27 trimethylation, mod_x0002_ulates chromatin structure and gene expression, and recruits DNA methyltrans_x0002_ferases for gene silencing.2 PCR,Western blot EZH2 Enhancer of zeste homolog 2 (EZH2), a catalytic component of the polycomb repressive complex 2, acts as a methyltrans_x0002_ferase for H3 lysine 27 trimethylation, mod_x0002_ulates chromatin structure and gene expression, and recruits DNA methyltrans_x0002_ferases for gene silencing.2 31641208 chr16 68734197 68736197 CDH1 Here, through comprehensive filtration, we prioritized rs7198799, a common SNP in the second intron of the CDH1, as the putative causal variant. In addition, we found an association of CRC_x0002_risk allele C of rs7198799 with elevated transcript level of biological plausible candidate gene ZFP90 via expression quantitative trait loci analysis. human blood High+Lowthroughput Enhancer of zeste homolog 2 enhances the migration and chemotaxis of dental mesenchymal stem cells 是 rs7198799 tumour E_01_0206 PCR,Western blot Here, through comprehensive filtration, we prioritized rs7198799, a common SNP in the second intron of the CDH1, as the putative causal variant. In addition, we found an association of CRC_x0002_risk allele C of rs7198799 with elevated transcript level of biological plausible candidate gene ZFP90 via expression quantitative trait loci analysis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, through comprehensive filtration, we prioritized rs7198799, a common SNP in the second intron of the CDH1, as the putative causal variant. In addition, we found an association of CRC_x0002_risk allele C of rs7198799 with elevated transcript level of biological plausible candidate gene ZFP90 via expression quantitative trait loci analysis. Immunohistochemical staining Here, through comprehensive filtration, we prioritized rs7198799, a common SNP in the second intron of the CDH1, as the putative causal variant. In addition, we found an association of CRC_x0002_risk allele C of rs7198799 with elevated transcript level of biological plausible candidate gene ZFP90 via expression quantitative trait loci analysis. PCR,Western blot CDH1 Here, through comprehensive filtration, we prioritized rs7198799, a common SNP in the second intron of the CDH1, as the putative causal variant. In addition, we found an association of CRC_x0002_risk allele C of rs7198799 with elevated transcript level of biological plausible candidate gene ZFP90 via expression quantitative trait loci analysis. 31636473 chr10 67881712 67883712 SIRT1 Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing human Epithelial High+Lowthroughput Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis 否 epithelial cell E_01_0207 Flow cytometry,PCR,Western blot Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing Immunohistochemical staining Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing Flow cytometry,PCR,Western blot SIRT1 Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing 31636429 chr5 70046788 70048788 SMN2 The adenine base was substi_x0002_tuted in the SMN2 mini-gene and the effect of these mutations was evaluated in human cellular models (Fig. 3a). human Epithelial High+Lowthroughput Structural basis of a small molecule targeting RNA for a specific splicing correction 否 Spinal muscular atrophy HEK293T E_01_0208 Western blot The adenine base was substi_x0002_tuted in the SMN2 mini-gene and the effect of these mutations was evaluated in human cellular models (Fig. 3a). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The adenine base was substi_x0002_tuted in the SMN2 mini-gene and the effect of these mutations was evaluated in human cellular models (Fig. 3a). Immunohistochemical staining The adenine base was substi_x0002_tuted in the SMN2 mini-gene and the effect of these mutations was evaluated in human cellular models (Fig. 3a). Western blot SMN2 The adenine base was substi_x0002_tuted in the SMN2 mini-gene and the effect of these mutations was evaluated in human cellular models (Fig. 3a). 31636200 chr4 110614447 110616447 PITX2 Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia,is associated with noncoding sequence variants located in proxim_x0002_ity to PITX2. human connective High+Lowthroughput Long-range Pitx2c enhancer-promoter interactions prevent predisposition to atrial fibrillation 是 rs2595104 Atrial fibrillation embryonic stem cell E_01_0209 Flow cytometry,PCR,Western blot Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia,is associated with noncoding sequence variants located in proxim_x0002_ity to PITX2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia,is associated with noncoding sequence variants located in proxim_x0002_ity to PITX2. Immunohistochemical staining Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia,is associated with noncoding sequence variants located in proxim_x0002_ity to PITX2. Flow cytometry,PCR,Western blot PITX2 Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia,is associated with noncoding sequence variants located in proxim_x0002_ity to PITX2. 31634421 chr16 92395428 92397428 Runx1 Runx1 is an important haematopoietic transcription factor as stressed by its involve_x0002_ment in a number of haematological malignancies. mouse blood High+Lowthroughput Gata3 targets Runx1 in the embryonic haematopoietic stem cell niche 否 Hematologic disorders hematopoietic stem cell E_01_0210 Flow cytometry,PCR,Western blot Runx1 is an important haematopoietic transcription factor as stressed by its involve_x0002_ment in a number of haematological malignancies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Runx1 is an important haematopoietic transcription factor as stressed by its involve_x0002_ment in a number of haematological malignancies. Immunohistochemical staining Runx1 is an important haematopoietic transcription factor as stressed by its involve_x0002_ment in a number of haematological malignancies. Flow cytometry,PCR,Western blot Runx1 Runx1 is an important haematopoietic transcription factor as stressed by its involve_x0002_ment in a number of haematological malignancies. 31633376 chr6 84684753 84686753 TBX18 Transcription factor TBX18 is a member of the TBX subfamily of the T-box family, which is involved in the formation and development of sinus node head. human Musculature High+Lowthroughput Transcription Factor TBX18 Reprograms Vascular Smooth Muscle Cells of Ascending Aorta to Pacemaker-Like Cells 否 smooth muscle cell E_01_0211 Flow cytometry, PCR, immunofluorescence staining Transcription factor TBX18 is a member of the TBX subfamily of the T-box family, which is involved in the formation and development of sinus node head. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcription factor TBX18 is a member of the TBX subfamily of the T-box family, which is involved in the formation and development of sinus node head. Immunohistochemical staining Transcription factor TBX18 is a member of the TBX subfamily of the T-box family, which is involved in the formation and development of sinus node head. Flow cytometry,PCR,免疫荧光染色 TBX18 Transcription factor TBX18 is a member of the TBX subfamily of the T-box family, which is involved in the formation and development of sinus node head. 31631026 chr1 23017098 23019098 KDM1A We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. human connective High+Lowthroughput Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG 否 Desmosomas melanoma cells E_01_0212 Western blot,PCR,Flow cytometry We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. Immunohistochemical staining We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. Western blot,PCR,Flow cytometry KDM1A We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. 31631012 chr2 209421458 209423458 MAP2 Specif_x0002_ically, examination of potential enhancers within these clusters that are located near neural marker genes, MAP2 (Herzog and Weber, 1978) and ROR2 (Endo et al., 2012), found them to be en_x0002_riched for ATAC-seq signal at 12–24 h, H3K27ac signal at 48–72h, and their expression to peak at 72 h (Figures S2A and S2B). human connective High+Lowthroughput Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction 是 rs2176546 pluripotent stem cell E_01_0213 Flow cytometry,PCR Specif_x0002_ically, examination of potential enhancers within these clusters that are located near neural marker genes, MAP2 (Herzog and Weber, 1978) and ROR2 (Endo et al., 2012), found them to be en_x0002_riched for ATAC-seq signal at 12–24 h, H3K27ac signal at 48–72h, and their expression to peak at 72 h (Figures S2A and S2B). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Specif_x0002_ically, examination of potential enhancers within these clusters that are located near neural marker genes, MAP2 (Herzog and Weber, 1978) and ROR2 (Endo et al., 2012), found them to be en_x0002_riched for ATAC-seq signal at 12–24 h, H3K27ac signal at 48–72h, and their expression to peak at 72 h (Figures S2A and S2B). Immunohistochemical staining Specif_x0002_ically, examination of potential enhancers within these clusters that are located near neural marker genes, MAP2 (Herzog and Weber, 1978) and ROR2 (Endo et al., 2012), found them to be en_x0002_riched for ATAC-seq signal at 12–24 h, H3K27ac signal at 48–72h, and their expression to peak at 72 h (Figures S2A and S2B). Flow cytometry,PCR MAP2,NANOG,ATF3 ROR2,POU5F1 Specif_x0002_ically, examination of potential enhancers within these clusters that are located near neural marker genes, MAP2 (Herzog and Weber, 1978) and ROR2 (Endo et al., 2012), found them to be en_x0002_riched for ATAC-seq signal at 12–24 h, H3K27ac signal at 48–72h, and their expression to peak at 72 h (Figures S2A and S2B).;Pluripotent markers (NANOG and POU5F1) and direct targets of transforming growth factor b (TGF-b) and bone morphogenetic protein (BMP) signaling(SMAD7, ID1, and LEFTY2) were downregulated, and immediate early genes (ATF3, FOS, FOSB, and EGR1/2/3) were transiently upregulated at 3 h, corresponding to the cell’s stress response against differentiation stimuli.;Pluripotent markers (NANOG and POU5F1) and direct targets of transforming growth factor b (TGF-b) and bone morphogenetic protein (BMP) signaling(SMAD7, ID1, and LEFTY2) were downregulated, and immediate early genes (ATF3, FOS, FOSB, and EGR1/2/3) were transiently upregulated at 3 h, corresponding to the cell’s stress response against differentiation stimuli. Specif_x0002_ically, examination of potential enhancers within these clusters that are located near neural marker genes, MAP2 (Herzog and Weber, 1978) and ROR2 (Endo et al., 2012), found them to be en_x0002_riched for ATAC-seq signal at 12–24 h, H3K27ac signal at 48–72h, and their expression to peak at 72 h (Figures S2A and S2B).;Pluripotent markers (NANOG and POU5F1) and direct targets of transforming growth factor b (TGF-b) and bone morphogenetic protein (BMP) signaling(SMAD7, ID1, and LEFTY2) were downregulated, and immediate early genes (ATF3, FOS, FOSB, and EGR1/2/3) were transiently upregulated at 3 h, corresponding to the cell’s stress response against differentiation stimuli. 31629814 chrX 47632617 47634617 ELK1 Furthermore, ELK1 supports cell-cycle entry during liver regeneration because Elk1-/- mice show reduced hepatocyte proliferation after PHx.40 human liver High+Lowthroughput The Dynamic Chromatin Architecture of the Regenerating Liver 否 Obesity hepatocyte E_01_0214 Flow cytometry,PCR Furthermore, ELK1 supports cell-cycle entry during liver regeneration because Elk1-/- mice show reduced hepatocyte proliferation after PHx.40 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, ELK1 supports cell-cycle entry during liver regeneration because Elk1-/- mice show reduced hepatocyte proliferation after PHx.40 Immunohistochemical staining Furthermore, ELK1 supports cell-cycle entry during liver regeneration because Elk1-/- mice show reduced hepatocyte proliferation after PHx.40 Flow cytometry,PCR KCNH4 Furthermore, ELK1 supports cell-cycle entry during liver regeneration because Elk1-/- mice show reduced hepatocyte proliferation after PHx.40 31629687 chr1 35867480 35869480 AGO1 A study showed AGO1 binding with RNA polymerase II and active promoters (Huang et al.,2013), while another report indicated that AGO1 association with active enhancers did not explain the observed widespread changes in gene expression in AGO1 depleted cells human liver High+Lowthroughput Nuclear AGO1 Regulates Gene Expression by Affecting Chromatin Architecture in Human Cells 否 cancer HepG2 cell E_01_0215 Western blot,Flow cytometry,PCR A study showed AGO1 binding with RNA polymerase II and active promoters (Huang et al.,2013), while another report indicated that AGO1 association with active enhancers did not explain the observed widespread changes in gene expression in AGO1 depleted cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A study showed AGO1 binding with RNA polymerase II and active promoters (Huang et al.,2013), while another report indicated that AGO1 association with active enhancers did not explain the observed widespread changes in gene expression in AGO1 depleted cells Immunohistochemical staining A study showed AGO1 binding with RNA polymerase II and active promoters (Huang et al.,2013), while another report indicated that AGO1 association with active enhancers did not explain the observed widespread changes in gene expression in AGO1 depleted cells Western blot,Flow cytometry,PCR AGO1 A study showed AGO1 binding with RNA polymerase II and active promoters (Huang et al.,2013), while another report indicated that AGO1 association with active enhancers did not explain the observed widespread changes in gene expression in AGO1 depleted cells 31628347 chr5 147234799 147236799 Cdx2 We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. mouse connective High+Lowthroughput Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells 否 Trophoblast stem cell E_01_0216 Flow cytometry We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. Immunohistochemical staining We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. Flow cytometry Cdx2,Tead4 We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated.;We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. 31623059 chr1 998360 1000360 ISG15 However, knockdown of lncRNA ISR had little effect on the expression of several ISGs, including myxovirus resistance protein A (MxA), Interferon-stimulated gene 15 (ISG15) and human 20-50-oligoadenylate synthetase 2 (OAS2) (Figure 3b). human blood High+Lowthroughput Identification of an Interferon-Stimulated Long Noncoding RNA (LncRNA ISR) Involved in Regulation of Influenza A Virus Replication 否 influenza B cell E_01_0217 PCR,Western blot However, knockdown of lncRNA ISR had little effect on the expression of several ISGs, including myxovirus resistance protein A (MxA), Interferon-stimulated gene 15 (ISG15) and human 20-50-oligoadenylate synthetase 2 (OAS2) (Figure 3b). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, knockdown of lncRNA ISR had little effect on the expression of several ISGs, including myxovirus resistance protein A (MxA), Interferon-stimulated gene 15 (ISG15) and human 20-50-oligoadenylate synthetase 2 (OAS2) (Figure 3b). Immunohistochemical staining However, knockdown of lncRNA ISR had little effect on the expression of several ISGs, including myxovirus resistance protein A (MxA), Interferon-stimulated gene 15 (ISG15) and human 20-50-oligoadenylate synthetase 2 (OAS2) (Figure 3b). PCR,Western blot ISG15 However, knockdown of lncRNA ISR had little effect on the expression of several ISGs, including myxovirus resistance protein A (MxA), Interferon-stimulated gene 15 (ISG15) and human 20-50-oligoadenylate synthetase 2 (OAS2) (Figure 3b). 31622687 chr3 101825749 101827749 NFKBIZ No alteration in NFKBIZ mRNA expression was observed in the PBMCs of the psoriatic patients during secukinumab treatment (Fig 3, B). human blood High+Lowthroughput IκBζ is a key player in the antipsoriatic effects of secukinumab 否 Psoriasis B cell E_01_0218 PCR,Western blot No alteration in NFKBIZ mRNA expression was observed in the PBMCs of the psoriatic patients during secukinumab treatment (Fig 3, B). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq No alteration in NFKBIZ mRNA expression was observed in the PBMCs of the psoriatic patients during secukinumab treatment (Fig 3, B). Immunohistochemical staining No alteration in NFKBIZ mRNA expression was observed in the PBMCs of the psoriatic patients during secukinumab treatment (Fig 3, B). PCR,Western blot NFKBIZ No alteration in NFKBIZ mRNA expression was observed in the PBMCs of the psoriatic patients during secukinumab treatment (Fig 3, B). 31621893 chr12 6531600 6533600 GAPDH The GAPDH/Gapdh served as an internal control for mRNA expression. The fold change in target mRNA expression was calculated using the equation 2−ΔΔCt . human liver High+Lowthroughput Costunolide represses hepatic fibrosis through WW domain-containing protein 2-mediated Notch3 degradation 否 hepatic stellate cell E_01_0219 PCR, Western blot, immunofluorescence staining The GAPDH/Gapdh served as an internal control for mRNA expression. The fold change in target mRNA expression was calculated using the equation 2−ΔΔCt . Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The GAPDH/Gapdh served as an internal control for mRNA expression. The fold change in target mRNA expression was calculated using the equation 2−ΔΔCt . Immunohistochemical staining The GAPDH/Gapdh served as an internal control for mRNA expression. The fold change in target mRNA expression was calculated using the equation 2−ΔΔCt . PCR,Western blot,免疫荧光染色 Gapdh GAPDH The GAPDH/Gapdh served as an internal control for mRNA expression. The fold change in target mRNA expression was calculated using the equation 2−ΔΔCt . The GAPDH/Gapdh served as an internal control for mRNA expression. The fold change in target mRNA expression was calculated using the equation 2−ΔΔCt . 31621133 chr17 42310525 42312525 STAT3 Via CSF1‐R and CD138, IL‐34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl‐xl and c‐Myc mediated by HBX. human liver High+Lowthroughput Interleukin-34 mediated by hepatitis B virus X protein via CCAAT/enhancer-binding protein α contributes to the proliferation and migration of hepatoma cells 否 liver cancer HCC cell E_01_0220 PCR, gene knockdown, Western blot Via CSF1‐R and CD138, IL‐34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl‐xl and c‐Myc mediated by HBX. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Via CSF1‐R and CD138, IL‐34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl‐xl and c‐Myc mediated by HBX. Immunohistochemical staining Via CSF1‐R and CD138, IL‐34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl‐xl and c‐Myc mediated by HBX. PCR,基因敲降,Western blot STAT3 Via CSF1‐R and CD138, IL‐34 promoted the proliferation and migration of hepatoma cells, and contributed to the activation of ERK and STAT3 pathways and the upregulation of Bcl‐xl and c‐Myc mediated by HBX. 31619507 chr4 147635062 147637062 PRMT9 Increased expression of PRMT isoforms, for example, PRMT1, CARM1, PRMT5, PRMT6, and PRMT9, in several tumor types has been correlated with poor overall survival. human lung High+Lowthroughput PRMT6 Promotes Lung Tumor Progression via the Alternate Activation of Tumor-Associated Macrophages 否 tumour NSCLC cell E_01_0221 PCR, gene knockdown, Western blot Increased expression of PRMT isoforms, for example, PRMT1, CARM1, PRMT5, PRMT6, and PRMT9, in several tumor types has been correlated with poor overall survival. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Increased expression of PRMT isoforms, for example, PRMT1, CARM1, PRMT5, PRMT6, and PRMT9, in several tumor types has been correlated with poor overall survival. Immunohistochemical staining Increased expression of PRMT isoforms, for example, PRMT1, CARM1, PRMT5, PRMT6, and PRMT9, in several tumor types has been correlated with poor overall survival. PCR,基因敲降,Western blot PRMT9 Increased expression of PRMT isoforms, for example, PRMT1, CARM1, PRMT5, PRMT6, and PRMT9, in several tumor types has been correlated with poor overall survival. 31619182 chr7 148804718 148806718 EZH2 In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. human blood High+Lowthroughput Inhibition of Polycomb Repressive Complex 2 activity reduces trimethylation of H3K27 and affects development in Arabidopsis seedlings 否 leukemia leukemic cell E_01_0222 PCR, Western blot, immunofluorescence staining In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. Immunohistochemical staining In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. PCR,Western blot,免疫荧光染色 EZH2 In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. 31618980 chr10 67881914 67883914 SIRT1 SIRT1 couples the deacetylation of various transcription factors and co- factors to the cleavage of NAD+, an indicator of cellular metabolic status, playing a vital role in metabolism, including fat storage, gluconeogenesis, fatty acid oxidation, lipogenesis, insulin secretion, food intake, circadian rhythm, and inflammation [40]. human Musculature High+Lowthroughput Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1 否 Obesity mouse cell of skeletal muscle E_01_0223 PCR,Western blot SIRT1 couples the deacetylation of various transcription factors and co- factors to the cleavage of NAD+, an indicator of cellular metabolic status, playing a vital role in metabolism, including fat storage, gluconeogenesis, fatty acid oxidation, lipogenesis, insulin secretion, food intake, circadian rhythm, and inflammation [40]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SIRT1 couples the deacetylation of various transcription factors and co- factors to the cleavage of NAD+, an indicator of cellular metabolic status, playing a vital role in metabolism, including fat storage, gluconeogenesis, fatty acid oxidation, lipogenesis, insulin secretion, food intake, circadian rhythm, and inflammation [40]. Immunohistochemical staining SIRT1 couples the deacetylation of various transcription factors and co- factors to the cleavage of NAD+, an indicator of cellular metabolic status, playing a vital role in metabolism, including fat storage, gluconeogenesis, fatty acid oxidation, lipogenesis, insulin secretion, food intake, circadian rhythm, and inflammation [40]. PCR,Western blot SIRT1 SIRT1 couples the deacetylation of various transcription factors and co- factors to the cleavage of NAD+, an indicator of cellular metabolic status, playing a vital role in metabolism, including fat storage, gluconeogenesis, fatty acid oxidation, lipogenesis, insulin secretion, food intake, circadian rhythm, and inflammation [40]. 31618627 chr12 2956471 2958471 TEAD4 Here, we mapped DSBs at high resolution in cancer and non-tumorigenic cells and found a transcrip_x0002_tion-coupled repair mechanism at oncogeni super_x0002_enhancers. At these super-enhancers the transcrip_x0002_tion factor TEAD4, together with various transcription factors and co-factors, co-localizes with the repair factor RAD51 of the homologous recombination pathway. human connective High+Lowthroughput Activation of Oncogenic Super-Enhancers Is Coupled with DNA Repair by RAD51 否 cancer E_01_0224 PCR,Flow cytometry Here, we mapped DSBs at high resolution in cancer and non-tumorigenic cells and found a transcrip_x0002_tion-coupled repair mechanism at oncogeni super_x0002_enhancers. At these super-enhancers the transcrip_x0002_tion factor TEAD4, together with various transcription factors and co-factors, co-localizes with the repair factor RAD51 of the homologous recombination pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we mapped DSBs at high resolution in cancer and non-tumorigenic cells and found a transcrip_x0002_tion-coupled repair mechanism at oncogeni super_x0002_enhancers. At these super-enhancers the transcrip_x0002_tion factor TEAD4, together with various transcription factors and co-factors, co-localizes with the repair factor RAD51 of the homologous recombination pathway. Immunohistochemical staining Here, we mapped DSBs at high resolution in cancer and non-tumorigenic cells and found a transcrip_x0002_tion-coupled repair mechanism at oncogeni super_x0002_enhancers. At these super-enhancers the transcrip_x0002_tion factor TEAD4, together with various transcription factors and co-factors, co-localizes with the repair factor RAD51 of the homologous recombination pathway. PCR,Flow cytometry TEAD4 Here, we mapped DSBs at high resolution in cancer and non-tumorigenic cells and found a transcrip_x0002_tion-coupled repair mechanism at oncogeni super_x0002_enhancers. At these super-enhancers the transcrip_x0002_tion factor TEAD4, together with various transcription factors and co-factors, co-localizes with the repair factor RAD51 of the homologous recombination pathway. 31616042 chr16 54280654 54282654 IRX3 The mechanism underlying the link between IRX3 and these conditions was since established using both 4-C and CRISPR-Cas9 based methods, which showed that the SNP in the FTO region de-repressed IRX3 expression, leading to altered energy metabolism and increased lipid storage [18, 19]. human connective High+Lowthroughput Understanding the genetics of neuropsychiatric disorders: the potential role of genomic regulatory blocks 是 rs75059851 tumour tumor cell E_01_0225 Flow cytometry The mechanism underlying the link between IRX3 and these conditions was since established using both 4-C and CRISPR-Cas9 based methods, which showed that the SNP in the FTO region de-repressed IRX3 expression, leading to altered energy metabolism and increased lipid storage [18, 19]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The mechanism underlying the link between IRX3 and these conditions was since established using both 4-C and CRISPR-Cas9 based methods, which showed that the SNP in the FTO region de-repressed IRX3 expression, leading to altered energy metabolism and increased lipid storage [18, 19]. Immunohistochemical staining The mechanism underlying the link between IRX3 and these conditions was since established using both 4-C and CRISPR-Cas9 based methods, which showed that the SNP in the FTO region de-repressed IRX3 expression, leading to altered energy metabolism and increased lipid storage [18, 19]. Flow cytometry IRX3,VRK2 The mechanism underlying the link between IRX3 and these conditions was since established using both 4-C and CRISPR-Cas9 based methods, which showed that the SNP in the FTO region de-repressed IRX3 expression, leading to altered energy metabolism and increased lipid storage [18, 19].;A notable example of an SNP involved in long-range reg_x0002_ulation of gene expression is a locus obtained by merging two SNPs in LD, with two nearby VRK2 and FANCL genes highlighted as putative targets of these variants. 31615896 chr17 39401537 39403537 MED1 In addition, other TFs and cofactors, such as KLFs, STAT5, PBX1, Krox20, AP1 , ATFs, GATA2/3 , TAF8 , and Mediator subunits (MED1, MED14 and NED23), have been reported to be involved in regulating either adipocyte commitment or differentiation in cell line and/or mouse models. human connective High+Lowthroughput The transcription factor NKX1-2 promotes adipogenesis and may contribute to a balance between adipocyte and osteoblast differentiation 否 Thyroid cancer ear mesenchymal stem cell E_01_0226 Western blot,PCR In addition, other TFs and cofactors, such as KLFs, STAT5, PBX1, Krox20, AP1 , ATFs, GATA2/3 , TAF8 , and Mediator subunits (MED1, MED14 and NED23), have been reported to be involved in regulating either adipocyte commitment or differentiation in cell line and/or mouse models. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, other TFs and cofactors, such as KLFs, STAT5, PBX1, Krox20, AP1 , ATFs, GATA2/3 , TAF8 , and Mediator subunits (MED1, MED14 and NED23), have been reported to be involved in regulating either adipocyte commitment or differentiation in cell line and/or mouse models. Immunohistochemical staining In addition, other TFs and cofactors, such as KLFs, STAT5, PBX1, Krox20, AP1 , ATFs, GATA2/3 , TAF8 , and Mediator subunits (MED1, MED14 and NED23), have been reported to be involved in regulating either adipocyte commitment or differentiation in cell line and/or mouse models. Western blot,PCR MED1 In addition, other TFs and cofactors, such as KLFs, STAT5, PBX1, Krox20, AP1 , ATFs, GATA2/3 , TAF8 , and Mediator subunits (MED1, MED14 and NED23), have been reported to be involved in regulating either adipocyte commitment or differentiation in cell line and/or mouse models. 31610176 chr6 131945597 131947597 CCN2 Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2. human connective High+Lowthroughput Insights into Fibroblast Plasticity: Cellular Communication Network 2 Is Required for Activation of Cancer-Associated Fibroblasts in a Murine Model of Melanoma 否 tumour melanoma cells E_01_0227 Flow cytometry,PCR,Western blot Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2. Immunohistochemical staining Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2. Flow cytometry,PCR,Western blot Sox2,ZFHX4 CCN2,BRAF Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2.;This resulted in a 9-gene score composed of the following genes: ZFHX4, DCN, ITGA11, COL6A3, COL1A1, ITGBL1, COL8A1, INHBA, and, MEG3. CAF-specific CCN2 scores were dichotimized with 13 receiver operating characteristics (ROC) curves to determine the optimal cutoff for the endpoint of overall survival censorship. Conversely, fibroblast activation was impaired in mice with a fibroblast-specific deletion of Ccn2, associated with reduced expression of alpha-smooth muscle actin and Sox2.;Although drugs, including those targeting specific mutations (eg, in BRAF) and checkpoint inhibitors, have been discovered that can retard melanoma progression in some patients, ultimately patients develop resistance to these regimens. 31608710 chr1 173855753 173857753 GAS5 The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) were transfected into RGCs after in vitro pressurization culture to exam the function of GAS5 in RGC apoptosis. human eye High+Lowthroughput Silencing of GAS5 Alleviates Glaucoma in Rat Models by Reducing Retinal Ganglion Cell Apoptosis 否 glaucoma retinal ganglion cell E_01_0228 PCR, Western blot, immunofluorescence light staining, flow cytometry The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) were transfected into RGCs after in vitro pressurization culture to exam the function of GAS5 in RGC apoptosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) were transfected into RGCs after in vitro pressurization culture to exam the function of GAS5 in RGC apoptosis. Immunohistochemical staining The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) were transfected into RGCs after in vitro pressurization culture to exam the function of GAS5 in RGC apoptosis. PCR,Western blot,免疫荧光光染色,Flow cytometry ABCA1 GAS5,EZH2 In addition, up-regulation of EZH2 promoted trimethylation of lysine 27 on histone H3, therefore suppressing ABCA1 expression, eventually leading to the inhibition of RGC apoptosis. The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) were transfected into RGCs after in vitro pressurization culture to exam the function of GAS5 in RGC apoptosis.;The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) were transfected into RGCs after in vitro pressurization culture to exam the function of GAS5 in RGC apoptosis. 31608546 chr6 88136910 88138910 CNR1 Previous studies have shown that the coding regions of the CNR1 gene, that encodes CB1, lack common non-synonymous polymorphisms that might account for differences in cannabinoid response. human connective High+Lowthroughput Disease-associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue-specific activity of the cannabinoid-1 receptor gene promoter; implications for cannabinoid pharmacogenetics 是 rs2023239 Obesity SH-SY5Y (human neuroblastoma cell) E_01_0229 PCR immunofluorescence staining Previous studies have shown that the coding regions of the CNR1 gene, that encodes CB1, lack common non-synonymous polymorphisms that might account for differences in cannabinoid response. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Previous studies have shown that the coding regions of the CNR1 gene, that encodes CB1, lack common non-synonymous polymorphisms that might account for differences in cannabinoid response. Immunohistochemical staining Previous studies have shown that the coding regions of the CNR1 gene, that encodes CB1, lack common non-synonymous polymorphisms that might account for differences in cannabinoid response. PCR免疫荧光染色 CNR1 Previous studies have shown that the coding regions of the CNR1 gene, that encodes CB1, lack common non-synonymous polymorphisms that might account for differences in cannabinoid response. 31606247 chr16 30955158 30957158 SETD1A Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions. human Nervous High+Lowthroughput Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice 是 Schizophrenia neural progenitor cell E_01_0230 Flow cytometry, PCR, immunofluorescence staining, Western blot Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions. Immunohistochemical staining Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions. Flow cytometry,PCR,免疫荧光染色,Western blot SETD1A Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions. 31605138 chr9 21964977 21966977 CDKN2A The existence of genetic risk factors common to NB and CMM has been suggested by the finding of the loss of function mutation E27X in CDKN2A in melanoma families who display NB (7). human blood High+Lowthroughput Neural crest-derived tumor neuroblastoma and melanoma share 1p13.2 as susceptibility locus that shows a long-range interaction with the SLC16A1 gene 是 rs2153977 cancer E_01_0231 Flow cytometry,PCR,Western blot The existence of genetic risk factors common to NB and CMM has been suggested by the finding of the loss of function mutation E27X in CDKN2A in melanoma families who display NB (7). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The existence of genetic risk factors common to NB and CMM has been suggested by the finding of the loss of function mutation E27X in CDKN2A in melanoma families who display NB (7). Immunohistochemical staining The existence of genetic risk factors common to NB and CMM has been suggested by the finding of the loss of function mutation E27X in CDKN2A in melanoma families who display NB (7). Flow cytometry,PCR,Western blot CDKN2A The existence of genetic risk factors common to NB and CMM has been suggested by the finding of the loss of function mutation E27X in CDKN2A in melanoma families who display NB (7). 31599948 chr12 4365800 4367800 FGF23 Fibroblast growth factor 23 (FGF23) is a newly dis_x0002_covered member of the endocrine subfamily of sys_x0002_temic FGF hormones that in humans include FGF19 and FGF21 (1, 2). human Epithelial High+Lowthroughput A Control Region Near the Fibroblast Growth Factor 23 Gene Mediates Response to Phosphate, 1,25(OH)2D3, and LPS In Vivo 否 cancer epithelial cell E_01_0232 PCR Fibroblast growth factor 23 (FGF23) is a newly dis_x0002_covered member of the endocrine subfamily of sys_x0002_temic FGF hormones that in humans include FGF19 and FGF21 (1, 2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Fibroblast growth factor 23 (FGF23) is a newly dis_x0002_covered member of the endocrine subfamily of sys_x0002_temic FGF hormones that in humans include FGF19 and FGF21 (1, 2). Immunohistochemical staining Fibroblast growth factor 23 (FGF23) is a newly dis_x0002_covered member of the endocrine subfamily of sys_x0002_temic FGF hormones that in humans include FGF19 and FGF21 (1, 2). PCR FGF23,CYP24A1,Cyp27b1 Fibroblast growth factor 23 (FGF23) is a newly dis_x0002_covered member of the endocrine subfamily of sys_x0002_temic FGF hormones that in humans include FGF19 and FGF21 (1, 2).;Accordingly, FGF23 has been shown to inhibit both the synthesis and se_x0002_cretion of PTH and to suppress CYP27B1 while induc_x0002_ing CYP24A1, the renal enzymes responsible for the synthesis and homeostatic maintenance of circulating 1,25(OH)2D3.;Be_x0002_cause both PTH and 1,25(OH)2D3 also modulate P homeostasis and PTH represents a primary inducer of the Cyp27b1 gene (11, 14, 15), these activities of FGF23 constitute key negative feedback loops that serve to limit the activity of both hormones in the target tissues de_x0002_scribed previously. 31595632 chr12 6531857 6533857 GAPDH The RNA concentration was detected by a microplate reader, and RNA was reverse transcribed to cDNA using the QIAGEN miRNA reverse transcription (miScript II RT Kit) and Thermo reverse transcription kits. Using cDNA as a template, the gene expression of U6, miR-326, C/EBPα, PPARγ, and GAPDH was detected by qPCR. human connective High+Lowthroughput The Role of miR-326 in Adipogenic Differentiation of Human Adipose-Derived Stem Cells by Targeting C/EBPα in vitro 否 Obesity mesenchymal stem cell E_01_0233 PCR, Western blot The RNA concentration was detected by a microplate reader, and RNA was reverse transcribed to cDNA using the QIAGEN miRNA reverse transcription (miScript II RT Kit) and Thermo reverse transcription kits. Using cDNA as a template, the gene expression of U6, miR-326, C/EBPα, PPARγ, and GAPDH was detected by qPCR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The RNA concentration was detected by a microplate reader, and RNA was reverse transcribed to cDNA using the QIAGEN miRNA reverse transcription (miScript II RT Kit) and Thermo reverse transcription kits. Using cDNA as a template, the gene expression of U6, miR-326, C/EBPα, PPARγ, and GAPDH was detected by qPCR. Immunohistochemical staining The RNA concentration was detected by a microplate reader, and RNA was reverse transcribed to cDNA using the QIAGEN miRNA reverse transcription (miScript II RT Kit) and Thermo reverse transcription kits. Using cDNA as a template, the gene expression of U6, miR-326, C/EBPα, PPARγ, and GAPDH was detected by qPCR. PCR, Western blot GAPDH The RNA concentration was detected by a microplate reader, and RNA was reverse transcribed to cDNA using the QIAGEN miRNA reverse transcription (miScript II RT Kit) and Thermo reverse transcription kits. Using cDNA as a template, the gene expression of U6, miR-326, C/EBPα, PPARγ, and GAPDH was detected by qPCR. 31592021 chr10 100370073 100372073 OLMALINC maturation-associated long intergenic noncoding RNA (OLMALINC) in a statin- and triglyceride (TG)- associated liver co-expression network using liver RNA sequencing (RNA-seq) from 259 Finnish patients who had undergone bariatric surgery. human liver High+Lowthroughput Novel Lipid Long Intervening Noncoding RNA, Oligodendrocyte Maturation-Associated Long Intergenic Noncoding RNA, Regulates the Liver Steatosis Gene Stearoyl-Coenzyme A Desaturase As an Enhancer RNA 否 liver cancer HepG2 cell E_01_0234 Flow cytometry,Western blot maturation-associated long intergenic noncoding RNA (OLMALINC) in a statin- and triglyceride (TG)- associated liver co-expression network using liver RNA sequencing (RNA-seq) from 259 Finnish patients who had undergone bariatric surgery. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq maturation-associated long intergenic noncoding RNA (OLMALINC) in a statin- and triglyceride (TG)- associated liver co-expression network using liver RNA sequencing (RNA-seq) from 259 Finnish patients who had undergone bariatric surgery. Immunohistochemical staining maturation-associated long intergenic noncoding RNA (OLMALINC) in a statin- and triglyceride (TG)- associated liver co-expression network using liver RNA sequencing (RNA-seq) from 259 Finnish patients who had undergone bariatric surgery. Flow cytometry,Western blot OLMALINC maturation-associated long intergenic noncoding RNA (OLMALINC) in a statin- and triglyceride (TG)- associated liver co-expression network using liver RNA sequencing (RNA-seq) from 259 Finnish patients who had undergone bariatric surgery. 31590652 chr12 7785003 7787003 NANOG We train our models on p300 co-activator binding sites; H1-specific, transcription factor binding sites (TFBS): NANOG, OCT4, and SOX2; and uncondensed, cleavage sensitive, DNase I Hypersensitivity Regions (DHS); which are all distal to TSS; as positive examples. human connective High+Lowthroughput AIKYATAN: mapping distal regulatory elements using convolutional learning on GPU 否 cancer embryonic stem cell E_01_0235 PCR We train our models on p300 co-activator binding sites; H1-specific, transcription factor binding sites (TFBS): NANOG, OCT4, and SOX2; and uncondensed, cleavage sensitive, DNase I Hypersensitivity Regions (DHS); which are all distal to TSS; as positive examples. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We train our models on p300 co-activator binding sites; H1-specific, transcription factor binding sites (TFBS): NANOG, OCT4, and SOX2; and uncondensed, cleavage sensitive, DNase I Hypersensitivity Regions (DHS); which are all distal to TSS; as positive examples. Immunohistochemical staining We train our models on p300 co-activator binding sites; H1-specific, transcription factor binding sites (TFBS): NANOG, OCT4, and SOX2; and uncondensed, cleavage sensitive, DNase I Hypersensitivity Regions (DHS); which are all distal to TSS; as positive examples. PCR NANOG We train our models on p300 co-activator binding sites; H1-specific, transcription factor binding sites (TFBS): NANOG, OCT4, and SOX2; and uncondensed, cleavage sensitive, DNase I Hypersensitivity Regions (DHS); which are all distal to TSS; as positive examples. 31589096 chr17 42697169 42699169 EZH1 Furthermore, the treatment of G. glabra root extract was also capable of augmenting the production of EZH1 in C666-1 cells (Figure 3(c)), thereby providing a potential mechanism that AK027294 silencing sup_x0002_presses C666-1 proliferation by increasing EZH1 expression levels. human nasopharynx High+Lowthroughput Glycyrrhiza glabra suppresses nasopharyngeal carcinoma cell proliferation through inhibiting the expression of lncRNA, AK027294 否 Nasopharyngeal carcinoma nasopharyngeal carcinoma cell E_01_0236 Western blot,Flow cytometry,PCR Furthermore, the treatment of G. glabra root extract was also capable of augmenting the production of EZH1 in C666-1 cells (Figure 3(c)), thereby providing a potential mechanism that AK027294 silencing sup_x0002_presses C666-1 proliferation by increasing EZH1 expression levels. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, the treatment of G. glabra root extract was also capable of augmenting the production of EZH1 in C666-1 cells (Figure 3(c)), thereby providing a potential mechanism that AK027294 silencing sup_x0002_presses C666-1 proliferation by increasing EZH1 expression levels. Immunohistochemical staining Furthermore, the treatment of G. glabra root extract was also capable of augmenting the production of EZH1 in C666-1 cells (Figure 3(c)), thereby providing a potential mechanism that AK027294 silencing sup_x0002_presses C666-1 proliferation by increasing EZH1 expression levels. Western blot,Flow cytometry,PCR EZH1 Furthermore, the treatment of G. glabra root extract was also capable of augmenting the production of EZH1 in C666-1 cells (Figure 3(c)), thereby providing a potential mechanism that AK027294 silencing sup_x0002_presses C666-1 proliferation by increasing EZH1 expression levels. 31588347 chr5 113018862 113020862 MCC Mucociliary clearance (MCC) in the respiratory tract acts as the first physical barrier of the innate immune defense mecha_x0002_nism, by which inhaled environmental stimuli, including microbes and irritants.5 MCC depends on two important con_x0002_stituents: mucus production and mucus transport. human Epithelial High+Lowthroughput Benzisothiazolinone upregulates the MUC5AC expression via ERK1/2, p38, and NF-κB pathways in airway epithelial cells 否 asthma epithelial cell E_01_0237 PCR,Western blot Mucociliary clearance (MCC) in the respiratory tract acts as the first physical barrier of the innate immune defense mecha_x0002_nism, by which inhaled environmental stimuli, including microbes and irritants.5 MCC depends on two important con_x0002_stituents: mucus production and mucus transport. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mucociliary clearance (MCC) in the respiratory tract acts as the first physical barrier of the innate immune defense mecha_x0002_nism, by which inhaled environmental stimuli, including microbes and irritants.5 MCC depends on two important con_x0002_stituents: mucus production and mucus transport. Immunohistochemical staining Mucociliary clearance (MCC) in the respiratory tract acts as the first physical barrier of the innate immune defense mecha_x0002_nism, by which inhaled environmental stimuli, including microbes and irritants.5 MCC depends on two important con_x0002_stituents: mucus production and mucus transport. PCR,Western blot MCC Mucociliary clearance (MCC) in the respiratory tract acts as the first physical barrier of the innate immune defense mecha_x0002_nism, by which inhaled environmental stimuli, including microbes and irritants.5 MCC depends on two important con_x0002_stituents: mucus production and mucus transport. 31588046 chr12 7785776 7787776 NANOG After 48 h of TGF-bi treatment, the transcriptional downre_x0002_gulation of key pluripotency genes, including NANOG, OCT4 (POU5F1), and PRDM14 was evident (Figure S1A) human connective High+Lowthroughput The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis 否 cancer cancer cell E_01_0238 Flow cytometry, PCR, immunofluorescence staining After 48 h of TGF-bi treatment, the transcriptional downre_x0002_gulation of key pluripotency genes, including NANOG, OCT4 (POU5F1), and PRDM14 was evident (Figure S1A) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq After 48 h of TGF-bi treatment, the transcriptional downre_x0002_gulation of key pluripotency genes, including NANOG, OCT4 (POU5F1), and PRDM14 was evident (Figure S1A) Immunohistochemical staining After 48 h of TGF-bi treatment, the transcriptional downre_x0002_gulation of key pluripotency genes, including NANOG, OCT4 (POU5F1), and PRDM14 was evident (Figure S1A) Flow cytometry,PCR,免疫荧光染色 NANOG After 48 h of TGF-bi treatment, the transcriptional downre_x0002_gulation of key pluripotency genes, including NANOG, OCT4 (POU5F1), and PRDM14 was evident (Figure S1A) 31588023 chr1 170660059 170662059 PRRX1 Motifs for the SE-associated TFs PRRX1, NFIC, and NFIX were enriched in both H3K27M sub_x0002_groups over normal pons (Figure 2D) human connective High+Lowthroughput Histone Variant and Cell Context Determine H3K27M Reprogramming of the Enhancer Landscape and Oncogenic State 否 Malignancy immune cell E_01_0239 Flow cytometry, PCR, immunofluorescence staining Motifs for the SE-associated TFs PRRX1, NFIC, and NFIX were enriched in both H3K27M sub_x0002_groups over normal pons (Figure 2D) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Motifs for the SE-associated TFs PRRX1, NFIC, and NFIX were enriched in both H3K27M sub_x0002_groups over normal pons (Figure 2D) Immunohistochemical staining Motifs for the SE-associated TFs PRRX1, NFIC, and NFIX were enriched in both H3K27M sub_x0002_groups over normal pons (Figure 2D) Flow cytometry,PCR,免疫荧光染色 PRRX1 Motifs for the SE-associated TFs PRRX1, NFIC, and NFIX were enriched in both H3K27M sub_x0002_groups over normal pons (Figure 2D) 31586130 chr3 194133931 194135931 HES1 Furthermore, NRARP overexpression blocked NOTCH transcriptional activity as shown by the overall decreased expression of NOTCH1 downstream tar_x0002_gets HES1 and DTX1 in NRARP-overexpressing cells (Fig. 1f). human blood High+Lowthroughput NRARP displays either pro- or anti-tumoral roles in T-cell acute lymphoblastic leukemia depending on Notch and Wnt signaling 否 Acute lymphoblastic leukemia T cell E_01_0240 PCR,Western blot Furthermore, NRARP overexpression blocked NOTCH transcriptional activity as shown by the overall decreased expression of NOTCH1 downstream tar_x0002_gets HES1 and DTX1 in NRARP-overexpressing cells (Fig. 1f). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, NRARP overexpression blocked NOTCH transcriptional activity as shown by the overall decreased expression of NOTCH1 downstream tar_x0002_gets HES1 and DTX1 in NRARP-overexpressing cells (Fig. 1f). Immunohistochemical staining Furthermore, NRARP overexpression blocked NOTCH transcriptional activity as shown by the overall decreased expression of NOTCH1 downstream tar_x0002_gets HES1 and DTX1 in NRARP-overexpressing cells (Fig. 1f). PCR,Western blot HES1 Furthermore, NRARP overexpression blocked NOTCH transcriptional activity as shown by the overall decreased expression of NOTCH1 downstream tar_x0002_gets HES1 and DTX1 in NRARP-overexpressing cells (Fig. 1f). 31584754 chr3 41191952 41193952 CTNNB1 It is well established that the central genetic event in the tumorigenesis of SPN is a gain-of-function mutation within the CTNNB1 gene that prevents β-catenin phos_x0002_phorylation and its subsequent proteasomal degradation through ubiquitination.1 human tumour High+Lowthroughput The usefulness of lymphoid enhancer-binding factor 1 and androgen receptor in diagnosing solid pseudopapillary neoplasm of the pancreas on cytopathology 否 tumour tumor cell E_01_0241 Immunohistochemistry It is well established that the central genetic event in the tumorigenesis of SPN is a gain-of-function mutation within the CTNNB1 gene that prevents β-catenin phos_x0002_phorylation and its subsequent proteasomal degradation through ubiquitination.1 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It is well established that the central genetic event in the tumorigenesis of SPN is a gain-of-function mutation within the CTNNB1 gene that prevents β-catenin phos_x0002_phorylation and its subsequent proteasomal degradation through ubiquitination.1 Immunohistochemical staining It is well established that the central genetic event in the tumorigenesis of SPN is a gain-of-function mutation within the CTNNB1 gene that prevents β-catenin phos_x0002_phorylation and its subsequent proteasomal degradation through ubiquitination.1 免疫组化 CTNNB1 It is well established that the central genetic event in the tumorigenesis of SPN is a gain-of-function mutation within the CTNNB1 gene that prevents β-catenin phos_x0002_phorylation and its subsequent proteasomal degradation through ubiquitination.1 31583122 chr11 35136216 35138216 CD44 It has been suggested that the expression of stem cell-associated markers, such as CD44 and Oct4, may support their roles in therapy evasion, tumor recur_x0002_rence, and metastasis11. human lung High+Lowthroughput Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer 否 Lung adenocarcinoma adenocarcinoma cell E_01_0242 PCR,Western blot It has been suggested that the expression of stem cell-associated markers, such as CD44 and Oct4, may support their roles in therapy evasion, tumor recur_x0002_rence, and metastasis11. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It has been suggested that the expression of stem cell-associated markers, such as CD44 and Oct4, may support their roles in therapy evasion, tumor recur_x0002_rence, and metastasis11. Immunohistochemical staining It has been suggested that the expression of stem cell-associated markers, such as CD44 and Oct4, may support their roles in therapy evasion, tumor recur_x0002_rence, and metastasis11. PCR,Western blot CD44 It has been suggested that the expression of stem cell-associated markers, such as CD44 and Oct4, may support their roles in therapy evasion, tumor recur_x0002_rence, and metastasis11. 31582835 chr7 148804794 148806794 EZH2 Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. human tumour High+Lowthroughput EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway 否 Medulloblastoma Medulloblastoma cell E_01_0243 PCR,Western blot Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. Immunohistochemical staining Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. PCR,Western blot EZH2 Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. 31581708 chr17 39726151 39728151 MIEN1 Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. human prostate High+Lowthroughput Migration and Invasion Enhancer 1 Is an NF-?B-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo 否 prostatic cancer prostate cancer cell E_01_0244 PCR,Western blot,Flow cytometry Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. Immunohistochemical staining Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. PCR,Western blot,Flow cytometry MIEN1,NDRG1 Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed.;Interleukin-6 (IL-6), a pluripotency cytokine, is involved in the malignant progression of prostate cancer [15,16], while N_x0002_myc downstream regulated 1 (NDRG1) is a tumor suppressor gene in numerous cancer cells [17], including prostate [18,19]. 31581661 chr8 127733019 127735019 MYC Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. human prostate High+Lowthroughput Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells 否 prostatic cancer prostate cancer cell E_01_0245 PCR Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. Immunohistochemical staining Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. PCR MYC Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. 31579913 chr20 63192571 63194571 YTHDF1 After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and human colon High+Lowthroughput Genetic variants in m6A modification genes are associated with colorectal cancer risk 是 rs118049207 Colon cancer Human colorectal carcinoma cell E_01_0246 PCR After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and Immunohistochemical staining After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and PCR YTHDF1,YTHDF3,YTHDF2,EIF3A After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and;After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and;After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and;After excluding genes located on the X chromosome, the resultant twenty related autosomal chromosome genes involved in the m6A modification of methylated RNA were obtained. Briefly, we included seven literatures (14,19,34-38), which described the YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), YTH N6-methyladenosine RNA binding protein 3 (YTHDF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTH domain-containing 1 (YTHDC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), eukaryotic translation initiation factor 3 subunit A (EIF3A), and 31579098 chr7 148804077 148806077 EZH2 The results demonstrated that different concen_x0002_trations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. human tumour High+Lowthroughput DZNep inhibits Hif-1α and Wnt signalling molecules to attenuate the proliferation and invasion of BGC-823 gastric cancer cells 否 tumour tumor cell E_01_0247 PCR,Western blot,Flow cytometry The results demonstrated that different concen_x0002_trations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results demonstrated that different concen_x0002_trations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. Immunohistochemical staining The results demonstrated that different concen_x0002_trations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. PCR,Western blot,Flow cytometry EZH2 The results demonstrated that different concen_x0002_trations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. 31573688 chr12 16545165 16547165 LMO3 LIM domain only 3 (LMO3), a member of the LIM_x0002_only protein group, enhances adipogenesis of human adipose-derived stromal cells by enhancing peroxisome proliferator-activated receptor γ (PPARG) transcriptional activity, and LMO3 is a specific regulator of human adipogenesis, but not of mouse, whose white adipocytes lack LMO3 expression. Moreover, LMO3 is upregulated in a tissue-specific manner in human obese visceral fat, and is an attractive target for interfering with human visceral obe_x0002_sity (Lindroos et al., 2013). human connective High+Lowthroughput Resveratrol Inhibits Human Visceral Preadipocyte Proliferation and Differentiation in vitro 否 diabetes 3T3-L1 cell E_01_0248 PCR,Western blot LIM domain only 3 (LMO3), a member of the LIM_x0002_only protein group, enhances adipogenesis of human adipose-derived stromal cells by enhancing peroxisome proliferator-activated receptor γ (PPARG) transcriptional activity, and LMO3 is a specific regulator of human adipogenesis, but not of mouse, whose white adipocytes lack LMO3 expression. Moreover, LMO3 is upregulated in a tissue-specific manner in human obese visceral fat, and is an attractive target for interfering with human visceral obe_x0002_sity (Lindroos et al., 2013). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LIM domain only 3 (LMO3), a member of the LIM_x0002_only protein group, enhances adipogenesis of human adipose-derived stromal cells by enhancing peroxisome proliferator-activated receptor γ (PPARG) transcriptional activity, and LMO3 is a specific regulator of human adipogenesis, but not of mouse, whose white adipocytes lack LMO3 expression. Moreover, LMO3 is upregulated in a tissue-specific manner in human obese visceral fat, and is an attractive target for interfering with human visceral obe_x0002_sity (Lindroos et al., 2013). Immunohistochemical staining LIM domain only 3 (LMO3), a member of the LIM_x0002_only protein group, enhances adipogenesis of human adipose-derived stromal cells by enhancing peroxisome proliferator-activated receptor γ (PPARG) transcriptional activity, and LMO3 is a specific regulator of human adipogenesis, but not of mouse, whose white adipocytes lack LMO3 expression. Moreover, LMO3 is upregulated in a tissue-specific manner in human obese visceral fat, and is an attractive target for interfering with human visceral obe_x0002_sity (Lindroos et al., 2013). PCR,Western blot LMO3 LIM domain only 3 (LMO3), a member of the LIM_x0002_only protein group, enhances adipogenesis of human adipose-derived stromal cells by enhancing peroxisome proliferator-activated receptor γ (PPARG) transcriptional activity, and LMO3 is a specific regulator of human adipogenesis, but not of mouse, whose white adipocytes lack LMO3 expression. Moreover, LMO3 is upregulated in a tissue-specific manner in human obese visceral fat, and is an attractive target for interfering with human visceral obe_x0002_sity (Lindroos et al., 2013). 31572429 chr22 41558440 41560440 CSDC2 Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR_x0002_373 in MCF-7 cells while not in HeLa cells. human breast High+Lowthroughput Purification and Identification of miRNA Target Sites in Genome Using DNA Affinity Precipitation 否 mammary cancer MCF-7 cell E_01_0249 Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR_x0002_373 in MCF-7 cells while not in HeLa cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR_x0002_373 in MCF-7 cells while not in HeLa cells. Immunohistochemical staining Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR_x0002_373 in MCF-7 cells while not in HeLa cells. CSDC2 Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR_x0002_373 in MCF-7 cells while not in HeLa cells. 31571902 chr22 15781801 15783801 DUXAP8 Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. human liver High+Lowthroughput Up-regulated long non-coding RNA DUXAP8 promotes cell growth through repressing Krüppel-like factor 2 expression in human hepatocellular carcinoma 否 liver cancer hepatocellular carcinoma cell E_01_0250 PCR Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. Immunohistochemical staining Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. PCR DUXAP8 Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. 31570750 chr1 10633990 10635990 CASZ1 This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a signifcant, reproducible, association with CVD (CEAP C≥2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P=1×10−98, PHet=0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. human kidney High+Lowthroughput A variant of the castor zinc finger 1 (CASZ1) gene is differentially associated with the clinical classification of chronic venous disease 是 rs11121615 Chronic venous disease HEK293 cell E_01_0251 PCR,Flow cytometry This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a signifcant, reproducible, association with CVD (CEAP C≥2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P=1×10−98, PHet=0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a signifcant, reproducible, association with CVD (CEAP C≥2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P=1×10−98, PHet=0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. Immunohistochemical staining This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a signifcant, reproducible, association with CVD (CEAP C≥2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P=1×10−98, PHet=0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. PCR,Flow cytometry CASZ1 This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a signifcant, reproducible, association with CVD (CEAP C≥2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P=1×10−98, PHet=0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. 31570746 chr13 40553093 40555093 FOXO1 Lastly, point mutations were induced in the binding sites of FOXO1 and HFH-3, enabling the exclusion of all the identifed and selected TFBSs. In this instance, enhancer activity was further downregulated human connective High+Lowthroughput Characterization of the Long Terminal Repeat of the Endogenous Retrovirus-derived microRNAs in the Olive Flounder 否 cancer cancer cell E_01_0252 PCR Lastly, point mutations were induced in the binding sites of FOXO1 and HFH-3, enabling the exclusion of all the identifed and selected TFBSs. In this instance, enhancer activity was further downregulated Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lastly, point mutations were induced in the binding sites of FOXO1 and HFH-3, enabling the exclusion of all the identifed and selected TFBSs. In this instance, enhancer activity was further downregulated Immunohistochemical staining Lastly, point mutations were induced in the binding sites of FOXO1 and HFH-3, enabling the exclusion of all the identifed and selected TFBSs. In this instance, enhancer activity was further downregulated PCR FOXO1 Lastly, point mutations were induced in the binding sites of FOXO1 and HFH-3, enabling the exclusion of all the identifed and selected TFBSs. In this instance, enhancer activity was further downregulated 31563853 chr3 186840138 186842138 ADIPOQ Relative to untreated control cells, T-brites had increased mRNA expression of PPARγ target genes (ADIPOQ, FABP3, FABP4, and RXRA) and brite/beige marker genes (PGC1α/β, PRDM16, CEBPβ, CIDEA, and ELOVL3), without expression changes in lipogenic genes (FASN and SCD1) (Figure S4a and S4b) human Fat High+Lowthroughput CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells 否 fat cell E_01_0253 Western blot, flow cytometry, PCR, immunofluorescence staining Relative to untreated control cells, T-brites had increased mRNA expression of PPARγ target genes (ADIPOQ, FABP3, FABP4, and RXRA) and brite/beige marker genes (PGC1α/β, PRDM16, CEBPβ, CIDEA, and ELOVL3), without expression changes in lipogenic genes (FASN and SCD1) (Figure S4a and S4b) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Relative to untreated control cells, T-brites had increased mRNA expression of PPARγ target genes (ADIPOQ, FABP3, FABP4, and RXRA) and brite/beige marker genes (PGC1α/β, PRDM16, CEBPβ, CIDEA, and ELOVL3), without expression changes in lipogenic genes (FASN and SCD1) (Figure S4a and S4b) Immunohistochemical staining Relative to untreated control cells, T-brites had increased mRNA expression of PPARγ target genes (ADIPOQ, FABP3, FABP4, and RXRA) and brite/beige marker genes (PGC1α/β, PRDM16, CEBPβ, CIDEA, and ELOVL3), without expression changes in lipogenic genes (FASN and SCD1) (Figure S4a and S4b) Western blot,Flow cytometry,PCR,免疫荧光染色 ADIPOQ Relative to untreated control cells, T-brites had increased mRNA expression of PPARγ target genes (ADIPOQ, FABP3, FABP4, and RXRA) and brite/beige marker genes (PGC1α/β, PRDM16, CEBPβ, CIDEA, and ELOVL3), without expression changes in lipogenic genes (FASN and SCD1) (Figure S4a and S4b) 31563432 chr4 154747879 154749879 Actrt2 Neither wild-type nor mutant b-catenin factors were found to occupy the typical enhancers of Actrt2 and Fam168b (Fig_x0002_ure S5B). mouse colon High+Lowthroughput Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes 否 Colon cancer HCT116 cells E_01_0254 Immunofluorescence light staining, flow cytometry, PCR Neither wild-type nor mutant b-catenin factors were found to occupy the typical enhancers of Actrt2 and Fam168b (Fig_x0002_ure S5B). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Neither wild-type nor mutant b-catenin factors were found to occupy the typical enhancers of Actrt2 and Fam168b (Fig_x0002_ure S5B). Immunohistochemical staining Neither wild-type nor mutant b-catenin factors were found to occupy the typical enhancers of Actrt2 and Fam168b (Fig_x0002_ure S5B). 免疫荧光光染色,Flow cytometry,PCR Actrt2 STAT3 Neither wild-type nor mutant b-catenin factors were found to occupy the typical enhancers of Actrt2 and Fam168b (Fig_x0002_ure S5B). Recent studies have shown that TFs and Mediator form phase_x0002_separated condensates at super-enhancers (Boija et al., 2018; Cho et al., 2018; Sabari et al., 2018), and the terminal signaling factors of the WNT, JAK/STAT, and TGF-b pathways (b-catenin, STAT3, and SMAD3, respectively) have been shown to preferen_x0002_tially occupy super-enhancers (Hnisz et al., 2015). 31561451 chr7 55016281 55018281 EGFR In vitro, we did not find a significant difference in nanoparticle binding to EGFR overexpressing head and neck cancer cells between EGFR-targeted and untargeted FITC-SiO2-NPs. human connective High+Lowthroughput Fluorescein- and EGFR-Antibody Conjugated Silica Nanoparticles for Enhancement of Real-time Tumor Border Definition Using Confocal Laser Endomicroscopy in Squamous Cell Carcinoma of the Head and Neck 否 tumour squamous cell E_01_0255 PCR, Western blot, immunofluorescence staining In vitro, we did not find a significant difference in nanoparticle binding to EGFR overexpressing head and neck cancer cells between EGFR-targeted and untargeted FITC-SiO2-NPs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In vitro, we did not find a significant difference in nanoparticle binding to EGFR overexpressing head and neck cancer cells between EGFR-targeted and untargeted FITC-SiO2-NPs. Immunohistochemical staining In vitro, we did not find a significant difference in nanoparticle binding to EGFR overexpressing head and neck cancer cells between EGFR-targeted and untargeted FITC-SiO2-NPs. PCR,Western blot,免疫荧光染色 EGFR In vitro, we did not find a significant difference in nanoparticle binding to EGFR overexpressing head and neck cancer cells between EGFR-targeted and untargeted FITC-SiO2-NPs. 31561366 chr11 47463063 47465063 CELF1 The DASHR overlap analysis found only one sncRNA overlap, where the variant rs4543938 in the CELF1 region overlapped the piRNA piR-56133. human blood High+Lowthroughput Fluorescein- and EGFR-Antibody Conjugated Silica Nanoparticles for Enhancement of Real-time Tumor Border Definition Using Confocal Laser Endomicroscopy in Squamous Cell Carcinoma of the Head and Neck 是 rs8093731 Chronic myeloid leukemia K562 cells E_01_0256 PCR,Flow cytometry The DASHR overlap analysis found only one sncRNA overlap, where the variant rs4543938 in the CELF1 region overlapped the piRNA piR-56133. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The DASHR overlap analysis found only one sncRNA overlap, where the variant rs4543938 in the CELF1 region overlapped the piRNA piR-56133. Immunohistochemical staining The DASHR overlap analysis found only one sncRNA overlap, where the variant rs4543938 in the CELF1 region overlapped the piRNA piR-56133. PCR,Flow cytometry CELF1,FERMT2 The DASHR overlap analysis found only one sncRNA overlap, where the variant rs4543938 in the CELF1 region overlapped the piRNA piR-56133.;Analysis of miRNA seed disruption found that 46 variants across 5 tag regions (CELF1, FERMT2, INPP5D, MS4A6A, and ZCWPW1) overlapped binding sites for 40 miRNAs in 11 target genes (Supplementary Table 2). 31560287 chr11 116832779 116834779 APOA1 Apolipoprotein A5 (ApoA5) has been shown as a vital regulator of lipid metabolism. Human APOA5 gene is located on the long arm of chromosome 11 adjacent to APOA1/APOC3/APOA4 gene clusters [7]. human Fat High+Lowthroughput New Insights into Apolipoprotein A5 and the Modulation of Human Adipose-derived Mesenchymal Stem Cells Adipogenesis 是 Obesity adipose-derived mesenchymal stem cells E_01_0257 PCR,Western blot Apolipoprotein A5 (ApoA5) has been shown as a vital regulator of lipid metabolism. Human APOA5 gene is located on the long arm of chromosome 11 adjacent to APOA1/APOC3/APOA4 gene clusters [7]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Apolipoprotein A5 (ApoA5) has been shown as a vital regulator of lipid metabolism. Human APOA5 gene is located on the long arm of chromosome 11 adjacent to APOA1/APOC3/APOA4 gene clusters [7]. Immunohistochemical staining Apolipoprotein A5 (ApoA5) has been shown as a vital regulator of lipid metabolism. Human APOA5 gene is located on the long arm of chromosome 11 adjacent to APOA1/APOC3/APOA4 gene clusters [7]. PCR,Western blot APOA1 Apolipoprotein A5 (ApoA5) has been shown as a vital regulator of lipid metabolism. Human APOA5 gene is located on the long arm of chromosome 11 adjacent to APOA1/APOC3/APOA4 gene clusters [7]. 31557715 chr7 25947403 25949403 MIR148A Physical map of the region showing the position of annotated genes, MIR148A and genetic polymorphisms (SNPs, annotated with their rs identifiers) associated with obesity and other related phenotypes human connective High+Lowthroughput Detailed Functional Characterization of a Waist-Hip Ratio Locus in 7p15.2 Defines an Enhancer Controlling Adipocyte Differentiation 是 rs1055144 liver cancer mesenchymal stem cell E_01_0258 PCR, flow cytometry, immunofluorescence staining Physical map of the region showing the position of annotated genes, MIR148A and genetic polymorphisms (SNPs, annotated with their rs identifiers) associated with obesity and other related phenotypes Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Physical map of the region showing the position of annotated genes, MIR148A and genetic polymorphisms (SNPs, annotated with their rs identifiers) associated with obesity and other related phenotypes Immunohistochemical staining Physical map of the region showing the position of annotated genes, MIR148A and genetic polymorphisms (SNPs, annotated with their rs identifiers) associated with obesity and other related phenotypes PCR,Flow cytometry,免疫荧光染色 MIR148A,SNX10,CHI3L1 Physical map of the region showing the position of annotated genes, MIR148A and genetic polymorphisms (SNPs, annotated with their rs identifiers) associated with obesity and other related phenotypes;The region is delimited by the distal gene NPVF and the proximal gene SNX10.;RNA-sequencing of cells with disrupted enhancer showed reduced expression of established adipocyte markers, such as ADIPOQ and LPL, and identified CHI3L1 on chromosome 1 as a potential gene involved in adipocyte differentiation. In conclusion, we identified and characterized an enhancer in the SNX10 locus, outlined its plausible mechanisms of action and downstream targets. 31554806 chr1 37806934 37808934 MTF1 PSIONIC-predicted activity for MTF1 in cell line models correlates with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy. Many identified TFs are significantly associated with survival outcome human breast High+Lowthroughput Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers 否 mammary cancer breast cancer cell E_01_0259 Flow cytometry PSIONIC-predicted activity for MTF1 in cell line models correlates with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy. Many identified TFs are significantly associated with survival outcome Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PSIONIC-predicted activity for MTF1 in cell line models correlates with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy. Many identified TFs are significantly associated with survival outcome Immunohistochemical staining PSIONIC-predicted activity for MTF1 in cell line models correlates with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy. Many identified TFs are significantly associated with survival outcome Flow cytometry MTF1 PSIONIC-predicted activity for MTF1 in cell line models correlates with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy. Many identified TFs are significantly associated with survival outcome 31551335 chr12 55963742 55965742 CDK2 HEAL-FUS complex binds the HIV promoter and enhances recruit_x0002_ment of the histone acetyltransferase p300, which positively regulates HIV transcrip_x0002_tion by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin_x0002_dependent kinase 2 gene, CDK2, to enhance CDK2 expression. human blood High+Lowthroughput The Long Noncoding RNA HEAL Regulates HIV-1 Replication through Epigenetic Regulation of the HIV-1 Promoter 否 AIDS blood mononuclear cells E_01_0260 Western blot,PCR HEAL-FUS complex binds the HIV promoter and enhances recruit_x0002_ment of the histone acetyltransferase p300, which positively regulates HIV transcrip_x0002_tion by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin_x0002_dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HEAL-FUS complex binds the HIV promoter and enhances recruit_x0002_ment of the histone acetyltransferase p300, which positively regulates HIV transcrip_x0002_tion by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin_x0002_dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Immunohistochemical staining HEAL-FUS complex binds the HIV promoter and enhances recruit_x0002_ment of the histone acetyltransferase p300, which positively regulates HIV transcrip_x0002_tion by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin_x0002_dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Western blot,PCR CDK2,NEAT1 HEAL-FUS complex binds the HIV promoter and enhances recruit_x0002_ment of the histone acetyltransferase p300, which positively regulates HIV transcrip_x0002_tion by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin_x0002_dependent kinase 2 gene, CDK2, to enhance CDK2 expression.;The first evidence that lncRNAs might be involved in HIV-1 replication came from experiments in the Jurkat T cell line, in which knockdown (KD) of NEAT1 increased viral production by enhancing the nuclear export of Rev-dependent instability element (INS)-containing HIV-1 mRNAs 31551256 chr9 134027777 134029777 BRD3 BRD3 is recruited to and controls the activity of a subset ERa transcriptional enhancers, providing a therapeu_x0002_tic opportunity to target BRD3 with BET inhibitors in ERa_x0002_positive breast cancers. human breast High+Lowthroughput Distinct Roles for BET Family Members in Estrogen Receptor α Enhancer Function and Gene Regulation in Breast Cancer Cells 否 mammary cancer breast cancer cell E_01_0261 Western blot,PCR,Flow cytometry BRD3 is recruited to and controls the activity of a subset ERa transcriptional enhancers, providing a therapeu_x0002_tic opportunity to target BRD3 with BET inhibitors in ERa_x0002_positive breast cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq BRD3 is recruited to and controls the activity of a subset ERa transcriptional enhancers, providing a therapeu_x0002_tic opportunity to target BRD3 with BET inhibitors in ERa_x0002_positive breast cancers. Immunohistochemical staining BRD3 is recruited to and controls the activity of a subset ERa transcriptional enhancers, providing a therapeu_x0002_tic opportunity to target BRD3 with BET inhibitors in ERa_x0002_positive breast cancers. Western blot,PCR,Flow cytometry BRD3 BRD3 is recruited to and controls the activity of a subset ERa transcriptional enhancers, providing a therapeu_x0002_tic opportunity to target BRD3 with BET inhibitors in ERa_x0002_positive breast cancers. 31551012 chr7 148804569 148806569 EZH2 Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing coun_x0002_teracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells human stomach High+Lowthroughput HOXD-AS1 confers cisplatin resistance in gastric cancer through epigenetically silencing PDCD4 via recruiting EZH2 否 gastric cancer gastric cancer cell E_01_0262 Western blot,PCR Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing coun_x0002_teracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing coun_x0002_teracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells Immunohistochemical staining Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing coun_x0002_teracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells Western blot,PCR PDCD4 EZH2 Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing coun_x0002_teracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing coun_x0002_teracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells 31547883 chr16 67559930 67561930 CTCF In the lysates from starved cells, the recip_x0002_rocal pull-down of CTCF and CGGBP1 was very weak. In lysates from stimulated cells, however, using CGGBP1 antibody we could pull down a major fraction of CTCF (Fig. 2b). human kidney High+Lowthroughput CGGBP1 regulates CTCF occupancy at repeats 否 HEK293T E_01_0263 Flow cytometry,PCR In the lysates from starved cells, the recip_x0002_rocal pull-down of CTCF and CGGBP1 was very weak. In lysates from stimulated cells, however, using CGGBP1 antibody we could pull down a major fraction of CTCF (Fig. 2b). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the lysates from starved cells, the recip_x0002_rocal pull-down of CTCF and CGGBP1 was very weak. In lysates from stimulated cells, however, using CGGBP1 antibody we could pull down a major fraction of CTCF (Fig. 2b). Immunohistochemical staining In the lysates from starved cells, the recip_x0002_rocal pull-down of CTCF and CGGBP1 was very weak. In lysates from stimulated cells, however, using CGGBP1 antibody we could pull down a major fraction of CTCF (Fig. 2b). Flow cytometry,PCR CTCF In the lysates from starved cells, the recip_x0002_rocal pull-down of CTCF and CGGBP1 was very weak. In lysates from stimulated cells, however, using CGGBP1 antibody we could pull down a major fraction of CTCF (Fig. 2b). 31545422 chr7 148804556 148806556 EZH2 In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. human neck High+Lowthroughput Targeting of EZH2 inhibits epithelial?mesenchymal transition in head and neck squamous cell carcinoma via regulating the STAT3/VEGFR2 axis 否 cancer neck squamous cell E_01_0264 PCR, Western blot, immunofluorescence staining In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. Immunohistochemical staining In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo. PCR,Western blot,免疫荧光染色 EZH2,STAT3 In this study, we found that inhibition of enhancer of zeste homolog 2 (EZH2) resulted in suppressed EMT in HNSCC in vitro and in vivo.;We reported that signal transducer and activator of transcription factor 3 (STAT3)/vascular endothelial growth factor receptor 2 (VEGFR2) axis served as the downstream signaling of EZH2 and mediated EMT in HNSCC. 31542774 chr19 29809345 29811345 CCNE1 By integrating SVs associated with acetylated chro_x0002_matin identified by paired-end NanoChIP-seq (PeNChIP-seq) with whole-genome sequencing (WGS) analysis of a large GC cohort, we observed enhancer hijacking events in GC targeting CCNE1, IGF2 and CCND1. human blood High+Lowthroughput Integrated paired-end enhancer profiling and whole-genome sequencing reveals recurrent CCNE1 and IGF2 enhancer hijacking in primary gastric adenocarcinoma 否 gastric cancer B cell E_01_0265 PCR,Flow cytometry By integrating SVs associated with acetylated chro_x0002_matin identified by paired-end NanoChIP-seq (PeNChIP-seq) with whole-genome sequencing (WGS) analysis of a large GC cohort, we observed enhancer hijacking events in GC targeting CCNE1, IGF2 and CCND1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By integrating SVs associated with acetylated chro_x0002_matin identified by paired-end NanoChIP-seq (PeNChIP-seq) with whole-genome sequencing (WGS) analysis of a large GC cohort, we observed enhancer hijacking events in GC targeting CCNE1, IGF2 and CCND1. Immunohistochemical staining By integrating SVs associated with acetylated chro_x0002_matin identified by paired-end NanoChIP-seq (PeNChIP-seq) with whole-genome sequencing (WGS) analysis of a large GC cohort, we observed enhancer hijacking events in GC targeting CCNE1, IGF2 and CCND1. PCR,Flow cytometry CCNE1 By integrating SVs associated with acetylated chro_x0002_matin identified by paired-end NanoChIP-seq (PeNChIP-seq) with whole-genome sequencing (WGS) analysis of a large GC cohort, we observed enhancer hijacking events in GC targeting CCNE1, IGF2 and CCND1. 31541592 chr6 35570844 35572844 FKBP5 We then carried out qRT‐PCR using primers of APP and FKBP5, a representative AR target gene, to evaluate their expression at the mRNA level. human bone High+Lowthroughput Amyloid precursor protein, an androgen-regulated gene, is targeted by RNA-binding protein PSF/SFPQ in neuronal cells 否 Osteoma SH‐SY5Y cells E_01_0266 PCR,Western blot We then carried out qRT‐PCR using primers of APP and FKBP5, a representative AR target gene, to evaluate their expression at the mRNA level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We then carried out qRT‐PCR using primers of APP and FKBP5, a representative AR target gene, to evaluate their expression at the mRNA level. Immunohistochemical staining We then carried out qRT‐PCR using primers of APP and FKBP5, a representative AR target gene, to evaluate their expression at the mRNA level. PCR,Western blot FKBP5 We then carried out qRT‐PCR using primers of APP and FKBP5, a representative AR target gene, to evaluate their expression at the mRNA level. 31538139 chr3 186839743 186841743 ADIPOQ The 50,336 ATAC-seq peaks that were more accessible in primary human adipocytes (‘adipocyte accessible’) included the promoters of the ADIPOQ and PPARGC1A genes with known adipocyte-spe_x0002_cific expression (Fig. 1c,d), providing evidence that we successfully differentiated adipocytes in vitro. human Fat High+Lowthroughput Reverse gene-environment interaction approach to identify variants influencing body-mass index in humans 是 rs10788522 fat cell E_01_0267 PCR,Flow cytometry The 50,336 ATAC-seq peaks that were more accessible in primary human adipocytes (‘adipocyte accessible’) included the promoters of the ADIPOQ and PPARGC1A genes with known adipocyte-spe_x0002_cific expression (Fig. 1c,d), providing evidence that we successfully differentiated adipocytes in vitro. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The 50,336 ATAC-seq peaks that were more accessible in primary human adipocytes (‘adipocyte accessible’) included the promoters of the ADIPOQ and PPARGC1A genes with known adipocyte-spe_x0002_cific expression (Fig. 1c,d), providing evidence that we successfully differentiated adipocytes in vitro. Immunohistochemical staining The 50,336 ATAC-seq peaks that were more accessible in primary human adipocytes (‘adipocyte accessible’) included the promoters of the ADIPOQ and PPARGC1A genes with known adipocyte-spe_x0002_cific expression (Fig. 1c,d), providing evidence that we successfully differentiated adipocytes in vitro. PCR,Flow cytometry ADIPOQ The 50,336 ATAC-seq peaks that were more accessible in primary human adipocytes (‘adipocyte accessible’) included the promoters of the ADIPOQ and PPARGC1A genes with known adipocyte-spe_x0002_cific expression (Fig. 1c,d), providing evidence that we successfully differentiated adipocytes in vitro. 31534142 chr16 67559649 67561649 CTCF To evaluate the specificity of epigenome editing systematically, we used ChIP-seq to map H3K9me3 and CTCF genome-wide in HEK293 cells after CTCF disruption by dCas9-KRAB (Fig. 1d, e). human kidney High+Lowthroughput Epigenome editing strategies for the functional annotation of CTCF insulators 否 tumour HEK293 cell E_01_0268 PCR,Flow cytometry To evaluate the specificity of epigenome editing systematically, we used ChIP-seq to map H3K9me3 and CTCF genome-wide in HEK293 cells after CTCF disruption by dCas9-KRAB (Fig. 1d, e). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To evaluate the specificity of epigenome editing systematically, we used ChIP-seq to map H3K9me3 and CTCF genome-wide in HEK293 cells after CTCF disruption by dCas9-KRAB (Fig. 1d, e). Immunohistochemical staining To evaluate the specificity of epigenome editing systematically, we used ChIP-seq to map H3K9me3 and CTCF genome-wide in HEK293 cells after CTCF disruption by dCas9-KRAB (Fig. 1d, e). PCR,Flow cytometry GSX2 CTCF,PDGFRA We found that the interaction between the GSX2 promoter and the PDGFRA insulator was reduced by disruption of the latter, albeit to a lesser extent than that observed for the PDGFRA promoter viewpoint. To evaluate the specificity of epigenome editing systematically, we used ChIP-seq to map H3K9me3 and CTCF genome-wide in HEK293 cells after CTCF disruption by dCas9-KRAB (Fig. 1d, e).;We found that the interaction between the GSX2 promoter and the PDGFRA insulator was reduced by disruption of the latter, albeit to a lesser extent than that observed for the PDGFRA promoter viewpoint. 31533028 chr21 34785012 34787012 RUNX1 The t(8;21) (q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoiet_x0002_ic master regulator RUNX1. human blood High+Lowthroughput RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction 否 leukemia hematopoietic stem cell E_01_0269 PCR,Flow cytometry The t(8;21) (q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoiet_x0002_ic master regulator RUNX1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The t(8;21) (q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoiet_x0002_ic master regulator RUNX1. Immunohistochemical staining The t(8;21) (q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoiet_x0002_ic master regulator RUNX1. PCR,Flow cytometry CCND2 RUNX1 Figure 2F shows an example of interactions at the upregulated CCND2 gene, which shows changes in interactions between its promoter and two up_x0002_stream distal elements (depicted in red). The t(8;21) (q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoiet_x0002_ic master regulator RUNX1. 31531679 chr16 86564387 86566387 FOXC2 FOXC2 is a transcription factor essential for inducing podocyte diferentiation, development and maturation, and is considered to be the earliest podocyte marker. human Epithelial High+Lowthroughput Evidence for miR-548c-5p regulation of FOXC2 transcription through a distal genomic target site in human podocytes 否 epithelial cell E_01_0270 PCR, Western blot, immunofluorescence staining FOXC2 is a transcription factor essential for inducing podocyte diferentiation, development and maturation, and is considered to be the earliest podocyte marker. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FOXC2 is a transcription factor essential for inducing podocyte diferentiation, development and maturation, and is considered to be the earliest podocyte marker. Immunohistochemical staining FOXC2 is a transcription factor essential for inducing podocyte diferentiation, development and maturation, and is considered to be the earliest podocyte marker. PCR,Western blot,免疫荧光染色 NPHS2,MTHFSD FOXC2 As the earliest podocyte marker, it has a prominent role in the diferen_x0002_tiation, development and maturation of podocytes, through the transcriptional regulation of a variety of diferent genes, such as podocin (NPHS2) [20, 22].;Schematic alignment of human vs mouse synteny of the miRNA target region. Head-to-head arrangement of MTHFSD and FOXC2 in mouse chromosome 8 corresponds to (or is syntenic to) human chromosome 16. FOXC2 is a transcription factor essential for inducing podocyte diferentiation, development and maturation, and is considered to be the earliest podocyte marker. 31530818 chr8 127732403 127734403 MYC FitHiChIP also captures previously validated enhancer interactions for several genes including MYC, TP53, and NMU. human blood High+Lowthroughput Identification of significant chromatin contacts from HiChIP data by FitHiChIP 否 leukemia T cell E_01_0271 Flow cytometry FitHiChIP also captures previously validated enhancer interactions for several genes including MYC, TP53, and NMU. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FitHiChIP also captures previously validated enhancer interactions for several genes including MYC, TP53, and NMU. Immunohistochemical staining FitHiChIP also captures previously validated enhancer interactions for several genes including MYC, TP53, and NMU. Flow cytometry MYC,TP53 FitHiChIP also captures previously validated enhancer interactions for several genes including MYC, TP53, and NMU.;FitHiChIP also captures previously validated enhancer interactions for several genes including MYC, TP53, and NMU. 31530812 chr2 24200308 24202308 ITSN2 In the PFC, according to the published transcriptome data of 16 PFC layers and the adjacent white matter48, the expression of ITSN2 is significantly lower in humans and chimpanzees than in rhesus macaques, consistent with their reduced H3K27Ac signals (an indication of enhancer activity) owing to the ASSV that disrupts an ADE in ITSN2 (Fig. 5c, d, g). human Nervous High+Lowthroughput Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants 是 neuronal cell E_01_0272 Flow cytometry,Western blot In the PFC, according to the published transcriptome data of 16 PFC layers and the adjacent white matter48, the expression of ITSN2 is significantly lower in humans and chimpanzees than in rhesus macaques, consistent with their reduced H3K27Ac signals (an indication of enhancer activity) owing to the ASSV that disrupts an ADE in ITSN2 (Fig. 5c, d, g). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the PFC, according to the published transcriptome data of 16 PFC layers and the adjacent white matter48, the expression of ITSN2 is significantly lower in humans and chimpanzees than in rhesus macaques, consistent with their reduced H3K27Ac signals (an indication of enhancer activity) owing to the ASSV that disrupts an ADE in ITSN2 (Fig. 5c, d, g). Immunohistochemical staining In the PFC, according to the published transcriptome data of 16 PFC layers and the adjacent white matter48, the expression of ITSN2 is significantly lower in humans and chimpanzees than in rhesus macaques, consistent with their reduced H3K27Ac signals (an indication of enhancer activity) owing to the ASSV that disrupts an ADE in ITSN2 (Fig. 5c, d, g). Flow cytometry,Western blot ITSN2,NEDD9 In the PFC, according to the published transcriptome data of 16 PFC layers and the adjacent white matter48, the expression of ITSN2 is significantly lower in humans and chimpanzees than in rhesus macaques, consistent with their reduced H3K27Ac signals (an indication of enhancer activity) owing to the ASSV that disrupts an ADE in ITSN2 (Fig. 5c, d, g).;Gene expression data of cerebellum in NHPs are not available to check its effect on NEDD9 expression 31530225 chr16 53698982 53700982 FTO FTO encodes an ortholog to the AlkB family of enzymes that demethylate nucleic acids human connective High+Lowthroughput Functional genomic characterization of the FTO locus in African Americans 是 rs9927317 Obesity mesenchymal stem cell E_01_0273 Flow cytometry FTO encodes an ortholog to the AlkB family of enzymes that demethylate nucleic acids Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FTO encodes an ortholog to the AlkB family of enzymes that demethylate nucleic acids Immunohistochemical staining FTO encodes an ortholog to the AlkB family of enzymes that demethylate nucleic acids Flow cytometry FTO,RPGRIP1L,IRX3,IRX5 CUX1 FTO encodes an ortholog to the AlkB family of enzymes that demethylate nucleic acids;The first intronic region of FTO is less than 100 bp 3’ from the transcriptional start site of the gene Retinitis Pigmentosa GTPase Regulator-Interacting Protein-1 Like (RPGRIP1L), a ciliary gene (24, 56) that is transcribed in the 5’ direction.;Other groups have shown that rs9930506 is associated with expression of IRX3 in the brain (39), as well as expression of both IRX3 and IRX5 in adipose tissue (7), with apparent biological relevance conveyed by physical interactions (chromosome conformation) with these genes’ promoters, although the resolution of this chromatin interaction data was not sufficient to detect (or rule out) interactions with RPGRIP1L.;Other groups have shown that rs9930506 is associated with expression of IRX3 in the brain (39), as well as expression of both IRX3 and IRX5 in adipose tissue (7), with apparent biological relevance conveyed by physical interactions (chromosome conformation) with these genes’ promoters, although the resolution of this chromatin interaction data was not sufficient to detect (or rule out) interactions with RPGRIP1L. We previously showed that rs8050136 resides within a putative binding site for the transcription factor Cut-like Homeobox 1 (CUX1) (46), which regulates expression of FTO and RPGRIP1L (43, 44). 31529763 chr17 43041465 43043465 BRCA1 Here we study how the N-terminal plastic region of Myc folds in complex with Max in the absence and presence of an E_x0002_box DNA fragment, and another intrinsically disordered binding partner, BRCA1. human High+Lowthroughput (19) F?NMR Spectroscopy Tagging and Paramagnetic Relaxation Enhancement-Based Conformation Analysis of Intrinsically Disordered Protein Complexes 否 tumour E-coli cell E_01_0274 Flow cytometry Here we study how the N-terminal plastic region of Myc folds in complex with Max in the absence and presence of an E_x0002_box DNA fragment, and another intrinsically disordered binding partner, BRCA1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we study how the N-terminal plastic region of Myc folds in complex with Max in the absence and presence of an E_x0002_box DNA fragment, and another intrinsically disordered binding partner, BRCA1. Immunohistochemical staining Here we study how the N-terminal plastic region of Myc folds in complex with Max in the absence and presence of an E_x0002_box DNA fragment, and another intrinsically disordered binding partner, BRCA1. Flow cytometry BRCA1 Here we study how the N-terminal plastic region of Myc folds in complex with Max in the absence and presence of an E_x0002_box DNA fragment, and another intrinsically disordered binding partner, BRCA1. 31525599 chr11 10302280 10304280 ADM ADMs were cut into disks with different diameters (4 mm and 8 mm) using a puncher, placed in a 24-well plate (Corning Costar) and ster_x0002_ilized with water (Millipore) containing 0.1 (v/v) peracetic acid and 4% (v/v) ethanol and incubated for 2 h at room temperature. human High+Lowthroughput Tracing upconversion nanoparticle penetration in human skin 否 E_01_0275 PCR, immunofluorescence staining ADMs were cut into disks with different diameters (4 mm and 8 mm) using a puncher, placed in a 24-well plate (Corning Costar) and ster_x0002_ilized with water (Millipore) containing 0.1 (v/v) peracetic acid and 4% (v/v) ethanol and incubated for 2 h at room temperature. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ADMs were cut into disks with different diameters (4 mm and 8 mm) using a puncher, placed in a 24-well plate (Corning Costar) and ster_x0002_ilized with water (Millipore) containing 0.1 (v/v) peracetic acid and 4% (v/v) ethanol and incubated for 2 h at room temperature. Immunohistochemical staining ADMs were cut into disks with different diameters (4 mm and 8 mm) using a puncher, placed in a 24-well plate (Corning Costar) and ster_x0002_ilized with water (Millipore) containing 0.1 (v/v) peracetic acid and 4% (v/v) ethanol and incubated for 2 h at room temperature. PCR,免疫荧光染色 ADM ADMs were cut into disks with different diameters (4 mm and 8 mm) using a puncher, placed in a 24-well plate (Corning Costar) and ster_x0002_ilized with water (Millipore) containing 0.1 (v/v) peracetic acid and 4% (v/v) ethanol and incubated for 2 h at room temperature. 31521883 chr18 63120882 63122882 BCL2 In experiment 4, the effect of trehalose treatment on the mRNA expression of lysosome-associated membrane protein 2 (LAMP2), porcine autophagy-related 5 (pATG5), LC3, BCL2 antagonist/ killer (Bak), BCL2 associated X (Bax), and B-cell lymphoma 2 (Bcl2) in cumulus cells and blastocysts were analyzed. human blood High+Lowthroughput Trehalose supplementation during porcine oocytes in?vitro maturation improves the developmental capacity of parthenotes 否 B cell E_01_0276 PCR, immunofluorescence staining In experiment 4, the effect of trehalose treatment on the mRNA expression of lysosome-associated membrane protein 2 (LAMP2), porcine autophagy-related 5 (pATG5), LC3, BCL2 antagonist/ killer (Bak), BCL2 associated X (Bax), and B-cell lymphoma 2 (Bcl2) in cumulus cells and blastocysts were analyzed. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In experiment 4, the effect of trehalose treatment on the mRNA expression of lysosome-associated membrane protein 2 (LAMP2), porcine autophagy-related 5 (pATG5), LC3, BCL2 antagonist/ killer (Bak), BCL2 associated X (Bax), and B-cell lymphoma 2 (Bcl2) in cumulus cells and blastocysts were analyzed. Immunohistochemical staining In experiment 4, the effect of trehalose treatment on the mRNA expression of lysosome-associated membrane protein 2 (LAMP2), porcine autophagy-related 5 (pATG5), LC3, BCL2 antagonist/ killer (Bak), BCL2 associated X (Bax), and B-cell lymphoma 2 (Bcl2) in cumulus cells and blastocysts were analyzed. PCR,免疫荧光染色 BCL2 In experiment 4, the effect of trehalose treatment on the mRNA expression of lysosome-associated membrane protein 2 (LAMP2), porcine autophagy-related 5 (pATG5), LC3, BCL2 antagonist/ killer (Bak), BCL2 associated X (Bax), and B-cell lymphoma 2 (Bcl2) in cumulus cells and blastocysts were analyzed. 31519749 chr3 142303842 142305842 XRN1 Insect-borne flaviviruses produce a 300- 500 base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5’-3’ exoribonuclease 1 (XRN1) via structures located in their 3’ UTRs. human High+Lowthroughput Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection 否 Villous carcinoma choriocarcinoma cells E_01_0277 PCR,Western blot Insect-borne flaviviruses produce a 300- 500 base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5’-3’ exoribonuclease 1 (XRN1) via structures located in their 3’ UTRs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Insect-borne flaviviruses produce a 300- 500 base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5’-3’ exoribonuclease 1 (XRN1) via structures located in their 3’ UTRs. Immunohistochemical staining Insect-borne flaviviruses produce a 300- 500 base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5’-3’ exoribonuclease 1 (XRN1) via structures located in their 3’ UTRs. PCR,Western blot XRN1 Insect-borne flaviviruses produce a 300- 500 base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5’-3’ exoribonuclease 1 (XRN1) via structures located in their 3’ UTRs. 31515496 chr16 67559926 67561926 CTCF By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and tran_x0002_scriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells. human prostate High+Lowthroughput A high-resolution 3D epigenomic map reveals insights into the creation of the prostate cancer transcriptome 是 prostatic cancer prostate cancer cell E_01_0278 PCR,Flow cytometry By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and tran_x0002_scriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and tran_x0002_scriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells. Immunohistochemical staining By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and tran_x0002_scriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells. PCR,Flow cytometry PRMT6,GABRB3 CTCF,FOXA1,TBX3 Examples of genes that belong to this cate_x0002_gory are TBX3 and PRMT6, which are known to be involved in prostate cancers23,24.;Moreover, we found that the size change of a TAD can be related to gene expression changes. For example, in normal cells, there is one large TAD at chromosome 15q12 containing the GABRB3 gene, which is not expressed in RWPE1. By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and tran_x0002_scriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells.;Moreover, we identify normal and prostate cancer-specific enhancer-promoter loops and involved transcription factors. For example, we show that FOXA1 is enriched in prostate cancer-specific enhancer_x0002_promoter loop anchors.;Examples of genes that belong to this cate_x0002_gory are TBX3 and PRMT6, which are known to be involved in prostate cancers23,24. 31514731 chr16 67559877 67561877 CTCF These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. human blood High+Lowthroughput The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance 是 leukemia K562 cell E_01_0279 PCR These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. Immunohistochemical staining These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. PCR CTCF These first en_x0002_hancers maintain more Hi-C interactions with other en_x0002_hancers and promoters, are more enriched for the loop factors CCCTC-binding factor (CTCF) and cohesin, and commonly overlap with the boundaries of chromatin loops. 31513772 chr9 21074265 21076265 IFNB1 We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). human uterus High+Lowthroughput The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers 否 cervical carcinoma HeLa cell E_01_0280 PCR, Western blot, flow cytometry, immunofluorescence staining We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). Immunohistochemical staining We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). PCR,Western blot,Flow cytometry,免疫荧光染色 IFNB1 We constructed IFNB1 luciferase reporter plasmids composed of IFNB1 immediate promoter followed by these enhancers (Figure S6D). 31509720 chr10 121475640 121477640 FGFR2 Fibroblast growth factor receptor 2 (FGFR2) in craniofacial bones mediates osteoprogenitor proliferation, differentiation, and apoptosis. human bone High+Lowthroughput Genetic Polymorphisms in FGFR2 Underlie Skeletal Malocclusion 是 rs2162540 Osteosarcoma MG-63 cell E_01_0281 Western blot,PCR,Flow cytometry Fibroblast growth factor receptor 2 (FGFR2) in craniofacial bones mediates osteoprogenitor proliferation, differentiation, and apoptosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Fibroblast growth factor receptor 2 (FGFR2) in craniofacial bones mediates osteoprogenitor proliferation, differentiation, and apoptosis. Immunohistochemical staining Fibroblast growth factor receptor 2 (FGFR2) in craniofacial bones mediates osteoprogenitor proliferation, differentiation, and apoptosis. Western blot,PCR,Flow cytometry FGFR2,RUNX2,SMAD4 Fibroblast growth factor receptor 2 (FGFR2) in craniofacial bones mediates osteoprogenitor proliferation, differentiation, and apoptosis.;That is, rs2162540 was significantly associated with skeletal class II malocclusion, while others were associated with skeletal class III malocclusion. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed that the common genotypes of rs2981578 and rs10736303 contained the binding sites of RUNX2 and SMAD4.;That is, rs2162540 was significantly associated with skeletal class II malocclusion, while others were associated with skeletal class III malocclusion. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed that the common genotypes of rs2981578 and rs10736303 contained the binding sites of RUNX2 and SMAD4. 31507631 chr11 65877171 65879171 CTSW This paper presents evidence that the breast_x0002_cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor_x0002_infiltrating lymphocytes. human connective High+Lowthroughput The Cancer-Associated Genetic Variant Rs3903072 Modulates Immune Cells in the Tumor Microenvironment 是 rs3903072 cancer immune cell E_01_0282 Flow cytometry,PCR This paper presents evidence that the breast_x0002_cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor_x0002_infiltrating lymphocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This paper presents evidence that the breast_x0002_cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor_x0002_infiltrating lymphocytes. Immunohistochemical staining This paper presents evidence that the breast_x0002_cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor_x0002_infiltrating lymphocytes. Flow cytometry,PCR CTSW This paper presents evidence that the breast_x0002_cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor_x0002_infiltrating lymphocytes. 31504407 chr6 151653980 151655980 ESR1 We observed ESR1 mRNA and ER protein down_x0002_regulation in BC cells treated with conditioned media (CM) from patient-derived, cancer-activated bone marrow stromal cells (BMSCs) and the BMSC cell line HS5. human breast High+Lowthroughput Bone Marrow Stromal Cells Transcriptionally Repress ESR1 but Cannot Overcome Constitutive ESR1 Mutant Activity 否 mammary cancer MCF7 cell E_01_0283 PCR, Western blot, immunofluorescence staining We observed ESR1 mRNA and ER protein down_x0002_regulation in BC cells treated with conditioned media (CM) from patient-derived, cancer-activated bone marrow stromal cells (BMSCs) and the BMSC cell line HS5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We observed ESR1 mRNA and ER protein down_x0002_regulation in BC cells treated with conditioned media (CM) from patient-derived, cancer-activated bone marrow stromal cells (BMSCs) and the BMSC cell line HS5. Immunohistochemical staining We observed ESR1 mRNA and ER protein down_x0002_regulation in BC cells treated with conditioned media (CM) from patient-derived, cancer-activated bone marrow stromal cells (BMSCs) and the BMSC cell line HS5. PCR,Western blot,免疫荧光染色 ESR1 We observed ESR1 mRNA and ER protein down_x0002_regulation in BC cells treated with conditioned media (CM) from patient-derived, cancer-activated bone marrow stromal cells (BMSCs) and the BMSC cell line HS5. 31503357 chrX 119233203 119235203 PGRMC1 Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot human prostate High+Lowthroughput Functional validation of metabolic genes that distinguish Gleason 3 from Gleason 4 prostate cancer foci 否 prostatic cancer prostate cancer cell E_01_0284 PCR,Western blot Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot Immunohistochemical staining Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot PCR,Western blot PGRMC1 Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot 31501538 chr8 95534429 95536429 Ccl17 We observed robust upregulation of immune marker genes associated with myeloid-derived suppressor cells (MDSCs) (Il10, Ifng, Csf1, Il6, Ptgs2 and Nfkb1), tumour-associ_x0002_ated macrophages (TAMs) (Ccl17, Ccl22, Il1r1, Il1a, Cxcl10 and Tnf) and tumour-associated neutrophils (TANs) (Cxcl1, Cxcl2, Cxcl5, Tnf and Il17a) (Supplementary Table 4) in colonic tumours from P. anaerobius-treated ApcMin/+. mouse colon High+Lowthroughput Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity 否 Colon cancer E_01_0285 Western blot,PCR We observed robust upregulation of immune marker genes associated with myeloid-derived suppressor cells (MDSCs) (Il10, Ifng, Csf1, Il6, Ptgs2 and Nfkb1), tumour-associ_x0002_ated macrophages (TAMs) (Ccl17, Ccl22, Il1r1, Il1a, Cxcl10 and Tnf) and tumour-associated neutrophils (TANs) (Cxcl1, Cxcl2, Cxcl5, Tnf and Il17a) (Supplementary Table 4) in colonic tumours from P. anaerobius-treated ApcMin/+. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We observed robust upregulation of immune marker genes associated with myeloid-derived suppressor cells (MDSCs) (Il10, Ifng, Csf1, Il6, Ptgs2 and Nfkb1), tumour-associ_x0002_ated macrophages (TAMs) (Ccl17, Ccl22, Il1r1, Il1a, Cxcl10 and Tnf) and tumour-associated neutrophils (TANs) (Cxcl1, Cxcl2, Cxcl5, Tnf and Il17a) (Supplementary Table 4) in colonic tumours from P. anaerobius-treated ApcMin/+. Immunohistochemical staining We observed robust upregulation of immune marker genes associated with myeloid-derived suppressor cells (MDSCs) (Il10, Ifng, Csf1, Il6, Ptgs2 and Nfkb1), tumour-associ_x0002_ated macrophages (TAMs) (Ccl17, Ccl22, Il1r1, Il1a, Cxcl10 and Tnf) and tumour-associated neutrophils (TANs) (Cxcl1, Cxcl2, Cxcl5, Tnf and Il17a) (Supplementary Table 4) in colonic tumours from P. anaerobius-treated ApcMin/+. Western blot,PCR Ccl17 We observed robust upregulation of immune marker genes associated with myeloid-derived suppressor cells (MDSCs) (Il10, Ifng, Csf1, Il6, Ptgs2 and Nfkb1), tumour-associ_x0002_ated macrophages (TAMs) (Ccl17, Ccl22, Il1r1, Il1a, Cxcl10 and Tnf) and tumour-associated neutrophils (TANs) (Cxcl1, Cxcl2, Cxcl5, Tnf and Il17a) (Supplementary Table 4) in colonic tumours from P. anaerobius-treated ApcMin/+. 31501517 chr19 46644863 46646863 DACT3 For instance, strong chromatin interactions were found between the DACT3 and AP2S1 promoter regions, and one significant eQTL, rs78730097 (NC_000019) for DACT3 was located in the AP2S1 promoter in the dorsolateral prefrontal cortex (Supplementary Fig. 10a) human connective High+Lowthroughput A compendium of promoter-centered long-range chromatin interactions in the human genome 是 embryonic cell E_01_0286 Flow cytometry,PCR For instance, strong chromatin interactions were found between the DACT3 and AP2S1 promoter regions, and one significant eQTL, rs78730097 (NC_000019) for DACT3 was located in the AP2S1 promoter in the dorsolateral prefrontal cortex (Supplementary Fig. 10a) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For instance, strong chromatin interactions were found between the DACT3 and AP2S1 promoter regions, and one significant eQTL, rs78730097 (NC_000019) for DACT3 was located in the AP2S1 promoter in the dorsolateral prefrontal cortex (Supplementary Fig. 10a) Immunohistochemical staining For instance, strong chromatin interactions were found between the DACT3 and AP2S1 promoter regions, and one significant eQTL, rs78730097 (NC_000019) for DACT3 was located in the AP2S1 promoter in the dorsolateral prefrontal cortex (Supplementary Fig. 10a) Flow cytometry,PCR DACT3 For instance, strong chromatin interactions were found between the DACT3 and AP2S1 promoter regions, and one significant eQTL, rs78730097 (NC_000019) for DACT3 was located in the AP2S1 promoter in the dorsolateral prefrontal cortex (Supplementary Fig. 10a) 31500558 chr7 18084316 18086316 HDAC9 Targeted resequencing of the HDAC9 locus in patients with atherosclerotic stroke and controls supported candidacy of rs2107595 as the causative single nucleotide polymorphism. A proteomic search for nuclear binding partners revealed preferential binding of the E2F3/TFDP1/Rb1 complex (E2F transcription factor 3/transcription factor Dp-1/Retinoblastoma 1) to the rs2107595 common allele, consistent with the disruption of an E2F3 consensus site by the risk allele. human connective High+Lowthroughput The Atherosclerosis Risk Variant rs2107595 Mediates Allele-Specific Transcriptional Regulation of HDAC9 via E2F3 and Rb1 是 rs2107595 atherosclerosis immune cell E_01_0287 Flow cytometry,PCR Targeted resequencing of the HDAC9 locus in patients with atherosclerotic stroke and controls supported candidacy of rs2107595 as the causative single nucleotide polymorphism. A proteomic search for nuclear binding partners revealed preferential binding of the E2F3/TFDP1/Rb1 complex (E2F transcription factor 3/transcription factor Dp-1/Retinoblastoma 1) to the rs2107595 common allele, consistent with the disruption of an E2F3 consensus site by the risk allele. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Targeted resequencing of the HDAC9 locus in patients with atherosclerotic stroke and controls supported candidacy of rs2107595 as the causative single nucleotide polymorphism. A proteomic search for nuclear binding partners revealed preferential binding of the E2F3/TFDP1/Rb1 complex (E2F transcription factor 3/transcription factor Dp-1/Retinoblastoma 1) to the rs2107595 common allele, consistent with the disruption of an E2F3 consensus site by the risk allele. Immunohistochemical staining Targeted resequencing of the HDAC9 locus in patients with atherosclerotic stroke and controls supported candidacy of rs2107595 as the causative single nucleotide polymorphism. A proteomic search for nuclear binding partners revealed preferential binding of the E2F3/TFDP1/Rb1 complex (E2F transcription factor 3/transcription factor Dp-1/Retinoblastoma 1) to the rs2107595 common allele, consistent with the disruption of an E2F3 consensus site by the risk allele. Flow cytometry,PCR HDAC9 Targeted resequencing of the HDAC9 locus in patients with atherosclerotic stroke and controls supported candidacy of rs2107595 as the causative single nucleotide polymorphism. A proteomic search for nuclear binding partners revealed preferential binding of the E2F3/TFDP1/Rb1 complex (E2F transcription factor 3/transcription factor Dp-1/Retinoblastoma 1) to the rs2107595 common allele, consistent with the disruption of an E2F3 consensus site by the risk allele. 31491956 chr7 55015564 55017564 EGFR ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs)pathway. human stomach High+Lowthroughput Lycopene Inhibits Activation of Epidermal Growth Factor Receptor and Expression of Cyclooxygenase-2 in Gastric Cancer Cells 否 gastric cancer gastric cancer cell E_01_0288 PCR,Western blot,Flow cytometry ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs)pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs)pathway. Immunohistochemical staining ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs)pathway. PCR,Western blot,Flow cytometry EGFR ROS are known to activate the epidermal growth factor receptor (EGFR), which causes the activation of the Ras/mitogen-activated protein kinases (MAPKs)pathway. 31481468 chr9 6410546 6412546 UHRF2 In mammals, SRA domains are found in only two proteins (15), the DNA methylation maintenance factor UHRF1 and the structurally related, but functionally distinct, UHRF2 (16, 17). human colon High+Lowthroughput The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation 否 Colon cancer colon cancer cell E_01_0289 Western blot In mammals, SRA domains are found in only two proteins (15), the DNA methylation maintenance factor UHRF1 and the structurally related, but functionally distinct, UHRF2 (16, 17). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In mammals, SRA domains are found in only two proteins (15), the DNA methylation maintenance factor UHRF1 and the structurally related, but functionally distinct, UHRF2 (16, 17). Immunohistochemical staining In mammals, SRA domains are found in only two proteins (15), the DNA methylation maintenance factor UHRF1 and the structurally related, but functionally distinct, UHRF2 (16, 17). Western blot UHRF2 In mammals, SRA domains are found in only two proteins (15), the DNA methylation maintenance factor UHRF1 and the structurally related, but functionally distinct, UHRF2 (16, 17). 31478258 chr7 148803962 148805962 EZH2 In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. human stomach High+Lowthroughput PCAT-1 contributes to cisplatin resistance in gastric cancer through epigenetically silencing PTEN via recruiting EZH2 否 gastric cancer gastric cancer cell E_01_0290 Western blot, PCR,Flow cytometry In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. Immunohistochemical staining In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. Western blot, PCR,Flow cytometry EZH2 In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. 30700785 chr17 31933934 31935934 SUZ12 PRC2 is composed of four main subunits; Suppressor of Zeste 12 (SUZ12), Retinoblastoma-Associated Protein 46/48 (RbAp46/48) human High+Lowthroughput The EZH2 SANT1 domain is a histone reader providing sensitivity to the modification state of the H4 tail 否 eukaryotic,HeLa,E. coli Rosetta2 (DE3) pLysS cell E_01_0291 ChIP-seq,Gateway Recombination cloning,EMSAs,HADDOCK Modeling PRC2 is composed of four main subunits; Suppressor of Zeste 12 (SUZ12), Retinoblastoma-Associated Protein 46/48 (RbAp46/48) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PRC2 is composed of four main subunits; Suppressor of Zeste 12 (SUZ12), Retinoblastoma-Associated Protein 46/48 (RbAp46/48) Immunohistochemical staining PRC2 is composed of four main subunits; Suppressor of Zeste 12 (SUZ12), Retinoblastoma-Associated Protein 46/48 (RbAp46/48) ChIP-seq,Gateway Recombination cloning,EMSAs,HADDOCK Modeling SUZ12 PRC2 is composed of four main subunits; Suppressor of Zeste 12 (SUZ12), Retinoblastoma-Associated Protein 46/48 (RbAp46/48) 30696717 chr4 71738822 71740822 GC Our classifiers also indicate that there are functionally relevant differences in enhancer and promoter GC content beyond the influence of CpG islands human Liver High+Lowthroughput Sequence Characteristics Distinguish Transcribed Enhancers from Promoters and Predict Their Breadth of Activity 否 common metabolic disorders E_01_0292 Western blot,Immunostaining,RT-PCR Our classifiers also indicate that there are functionally relevant differences in enhancer and promoter GC content beyond the influence of CpG islands Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our classifiers also indicate that there are functionally relevant differences in enhancer and promoter GC content beyond the influence of CpG islands Immunohistochemical staining Our classifiers also indicate that there are functionally relevant differences in enhancer and promoter GC content beyond the influence of CpG islands Western blot,Immunostaining,RT-PCR GC Our classifiers also indicate that there are functionally relevant differences in enhancer and promoter GC content beyond the influence of CpG islands 30692044 chr10 100732827 100734827 PAX2 To generate the recombinant lentivirus, lentiviral pLKO-shAR/pLKO-Scr with pMD2.G packaging and psPAX2 envelope plasmids human prostate High+Lowthroughput Preclinical study using androgen receptor (AR) degradation enhancer to increase radiotherapy efficacy via targeting radiation-increased AR to better suppress prostate cancer progression Prostate cancer E_01_0293 PCR,Western blot To generate the recombinant lentivirus, lentiviral pLKO-shAR/pLKO-Scr with pMD2.G packaging and psPAX2 envelope plasmids Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To generate the recombinant lentivirus, lentiviral pLKO-shAR/pLKO-Scr with pMD2.G packaging and psPAX2 envelope plasmids Immunohistochemical staining To generate the recombinant lentivirus, lentiviral pLKO-shAR/pLKO-Scr with pMD2.G packaging and psPAX2 envelope plasmids PCR,Western blot PAX2 To generate the recombinant lentivirus, lentiviral pLKO-shAR/pLKO-Scr with pMD2.G packaging and psPAX2 envelope plasmids 33147208 chr9 21074558 21076558 IFNB1 This variant prevents binding of the C/EBP-β transcription factor, and is associated with decreased expression of IFNB1 in activated monocytes. human Epithelial High+Lowthroughput A genetic variant controls interferon-尾 gene expression in human myeloid cells by preventing C/EBP-尾 binding on a conserved enhancer 是 monocyte cells E_01_0294 Flow cytometry This variant prevents binding of the C/EBP-β transcription factor, and is associated with decreased expression of IFNB1 in activated monocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This variant prevents binding of the C/EBP-β transcription factor, and is associated with decreased expression of IFNB1 in activated monocytes. Immunohistochemical staining This variant prevents binding of the C/EBP-β transcription factor, and is associated with decreased expression of IFNB1 in activated monocytes. 流式细胞术 IFNB1 This variant prevents binding of the C/EBP-β transcription factor, and is associated with decreased expression of IFNB1 in activated monocytes. 30688289 chr4 73737463 73739463 CXCL8 Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine the expressions of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), apoptosis-related genes, and the downstream target genes of NF-κB signaling pathway, including NFKBIA, CXCL8, and cyclin D1. human Kidney High+Lowthroughput The Effect of Overexpression of the Enhancer of Zeste Homolog 1 (EZH1) Gene on Aristolochic Acid-Induced Injury in HK-2 Human Kidney Proximal Tubule Cells In Vitro Acute kidney injury Human Kidney Proximal Tubule cell E_01_0295 PCR, Western blots, sequencing technology Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine the expressions of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), apoptosis-related genes, and the downstream target genes of NF-κB signaling pathway, including NFKBIA, CXCL8, and cyclin D1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine the expressions of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), apoptosis-related genes, and the downstream target genes of NF-κB signaling pathway, including NFKBIA, CXCL8, and cyclin D1. Immunohistochemical staining Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine the expressions of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), apoptosis-related genes, and the downstream target genes of NF-κB signaling pathway, including NFKBIA, CXCL8, and cyclin D1. PCR，Western blots,测序技术 CXCL8 Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine the expressions of inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), apoptosis-related genes, and the downstream target genes of NF-κB signaling pathway, including NFKBIA, CXCL8, and cyclin D1. 30683753 chr3 133743339 133745339 TF This higher tissue specificity is strongly associated with having less complex transcription factor (TF) motif profiles at the core promoter. human Liver High+Lowthroughput High-throughput functional analysis of lncRNA core promoters elucidates rules governing tissue specificity common metabolic disorders E_01_0296 Western blot,Immunostaining,RT-PCR This higher tissue specificity is strongly associated with having less complex transcription factor (TF) motif profiles at the core promoter. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This higher tissue specificity is strongly associated with having less complex transcription factor (TF) motif profiles at the core promoter. Immunohistochemical staining This higher tissue specificity is strongly associated with having less complex transcription factor (TF) motif profiles at the core promoter. Western blot,Immunostaining,RT-PCR TF This higher tissue specificity is strongly associated with having less complex transcription factor (TF) motif profiles at the core promoter. 30683142 chr17 43041963 43043963 BRCA1 o provide insights into alternative classification and potential therapeutic targeting strategies of BRCA1-like hormone-receptor-positive tumors we developed and applied a novel copy number classifier to identify BRCA1-like hormone-receptor-positive tumors and their characteristic somatic alteration profiles. human Breast High+Lowthroughput Molecular and epigenetic profiles of BRCA1-like hormone-receptor-positive breast tumors identified with development and application of a copy-number-based classifier mammary cancer breast cancer cell E_01_0297 PCR, sequencing technology o provide insights into alternative classification and potential therapeutic targeting strategies of BRCA1-like hormone-receptor-positive tumors we developed and applied a novel copy number classifier to identify BRCA1-like hormone-receptor-positive tumors and their characteristic somatic alteration profiles. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq o provide insights into alternative classification and potential therapeutic targeting strategies of BRCA1-like hormone-receptor-positive tumors we developed and applied a novel copy number classifier to identify BRCA1-like hormone-receptor-positive tumors and their characteristic somatic alteration profiles. Immunohistochemical staining o provide insights into alternative classification and potential therapeutic targeting strategies of BRCA1-like hormone-receptor-positive tumors we developed and applied a novel copy number classifier to identify BRCA1-like hormone-receptor-positive tumors and their characteristic somatic alteration profiles. PCR，测序技术 BRCA1 o provide insights into alternative classification and potential therapeutic targeting strategies of BRCA1-like hormone-receptor-positive tumors we developed and applied a novel copy number classifier to identify BRCA1-like hormone-receptor-positive tumors and their characteristic somatic alteration profiles. 30682089 chr15 72964799 72966799 Ago2 One strand then incorporates with Argonaute (Ago2) proteins into the RNA Inducing Silencing Complex (RISC) mouse lymph High+Lowthroughput HIV-1 infection increases microRNAs that inhibit Dicer1, HRB and HIV-EP2, thereby reducing viral replication AIDS Sup-T1 cell，HeLa-MAGI cell E_01_0298 PCR, Western blot, sequencing technology One strand then incorporates with Argonaute (Ago2) proteins into the RNA Inducing Silencing Complex (RISC) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq One strand then incorporates with Argonaute (Ago2) proteins into the RNA Inducing Silencing Complex (RISC) Immunohistochemical staining One strand then incorporates with Argonaute (Ago2) proteins into the RNA Inducing Silencing Complex (RISC) PCR，Western blot，测序技术 Ago2 One strand then incorporates with Argonaute (Ago2) proteins into the RNA Inducing Silencing Complex (RISC) 30678091 chr15 99562775 99564775 MEF2A The strongest effect visible in three distinct cell types was observed for rs12946510 that is predicted to alter MEF2A/C and FOXO1 binding sites. human lymph High+Lowthroughput Functional SNPs in the Human Autoimmunity-Associated Locus 17q12-21 mammary cancer immune cell E_01_0299 PCR，Western blot，ChIP-seq The strongest effect visible in three distinct cell types was observed for rs12946510 that is predicted to alter MEF2A/C and FOXO1 binding sites. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The strongest effect visible in three distinct cell types was observed for rs12946510 that is predicted to alter MEF2A/C and FOXO1 binding sites. Immunohistochemical staining The strongest effect visible in three distinct cell types was observed for rs12946510 that is predicted to alter MEF2A/C and FOXO1 binding sites. PCR，Western blot，ChIP-seq MEF2A The strongest effect visible in three distinct cell types was observed for rs12946510 that is predicted to alter MEF2A/C and FOXO1 binding sites. 30676242 chr14 64081786 64083786 ESR2 They were also more likely to be in ARNT and ESR2 transcription factor binding sites human lymph High+Lowthroughput Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood Autoimmune diseases B cell E_01_0300 ChIP-seq They were also more likely to be in ARNT and ESR2 transcription factor binding sites Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq They were also more likely to be in ARNT and ESR2 transcription factor binding sites Immunohistochemical staining They were also more likely to be in ARNT and ESR2 transcription factor binding sites ChIP-seq ESR2 They were also more likely to be in ARNT and ESR2 transcription factor binding sites 30675263 chr13 73052370 73054370 KLF5 In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. human lymph High+Lowthroughput Association of the invasiveness of colon cancer with the expression of C/EBPα Colon cancer SW480 cell，CC cell E_01_0301 PCR，ChIP-Seq In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. Immunohistochemical staining In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. PCR，ChIP-Seq KLF5 In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. 30672466 chr11 114255412 114257412 NNMT Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. human bone High+Lowthroughput PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells E_01_0302 PCR，Western blot，ChIP-seq Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. Immunohistochemical staining Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. PCR，Western blot，ChIP-seq NNMT Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. 34529725 chr7 128935299 128937299 IRF5 Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases human Renal High+Lowthroughput A comprehensive integrated post-GWAS analysis of Type 1 diabetes reveals enhancer_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_based immune dysregulation 有 Type 1 diabetes E_01_0303 Gel electrophoresis Western blot flow cytometry chip Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases Immunohistochemical staining Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases 凝胶电泳 Western blot 流式细胞术 CHIP IRF5 Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases 30670628 chr6 43767278 43769278 VEGFA Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network human endothelial High+Lowthroughput A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA endothelial cell E_01_0304 PCR，Western blot，ChIP-seq Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network Immunohistochemical staining Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network PCR，Western blot，ChIP-seq VEGFA Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network 30670569 chrX 55006658 55008658 ALAS2 we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene human blood High+Lowthroughput Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation anemia E_01_0305 PCR，Western blot，ChIP-seq we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene Immunohistochemical staining we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene PCR，Western blot，ChIP-seq ALAS2 we first generated mutant mice by disrupting the GATA-1 binding motif at the intron 1 enhancer of the ALAS2 gene 30664779 chr5 69231799 69233799 CDK7 These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. human bone High+Lowthroughput Small-molecule targeting of brachyury transcription factor addiction in chordoma chordoma chordoma cell E_01_0306 PCR，ChIP-seq These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. Immunohistochemical staining These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. PCR，ChIP-seq CDK7 These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. 30664211 chr1 153387368 153389368 S100A8 The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region human epithelial High+Lowthroughput Expression of S100A8 is induced by interleukin?1α in TR146 epithelial cells through a mechanism involving CCAAT/enhancer binding protein β Infection of mucosal epithelial cells TR146 epithelial cell E_01_0307 PCR, Western blot, chip SEQ bioinformatic prediction The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region Immunohistochemical staining The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region PCR，Western blot，ChIP-seq生物信息预测 S100A8 The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region 30664173 chr9 117701433 117703433 TLR4 The cell proliferation rate and inflammatory cytokine expression of PBMCs treated with the FimA fusion protein with or without transfection with toll‑like receptor 4 (TLR4) small interfering (si)RNA were detected by CCK‑8 assays and ELISAs, respectively. human blood High+Lowthroughput Recombinant fimbriae protein of Porphyromonas gingivalis induces an inflammatory response via the TLR4/NF?κB signaling pathway in human peripheral blood mononuclear cells Periodontal disease peripheral blood mononuclear cell E_01_0308 PCR, Western blot, sequencing technology The cell proliferation rate and inflammatory cytokine expression of PBMCs treated with the FimA fusion protein with or without transfection with toll‑like receptor 4 (TLR4) small interfering (si)RNA were detected by CCK‑8 assays and ELISAs, respectively. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The cell proliferation rate and inflammatory cytokine expression of PBMCs treated with the FimA fusion protein with or without transfection with toll‑like receptor 4 (TLR4) small interfering (si)RNA were detected by CCK‑8 assays and ELISAs, respectively. Immunohistochemical staining The cell proliferation rate and inflammatory cytokine expression of PBMCs treated with the FimA fusion protein with or without transfection with toll‑like receptor 4 (TLR4) small interfering (si)RNA were detected by CCK‑8 assays and ELISAs, respectively. PCR，Western blot，测序技术 TLR4 The cell proliferation rate and inflammatory cytokine expression of PBMCs treated with the FimA fusion protein with or without transfection with toll‑like receptor 4 (TLR4) small interfering (si)RNA were detected by CCK‑8 assays and ELISAs, respectively. 30662920 chr6 137864227 137866227 TNFAIP3 The TNFAIP3 gene encodes the A20 protein essential for the development and functional performance of dendritic, B and T cells and macrophages as well as an important negative feedback regulator of the NF-κB pathway human lymph High+Lowthroughput TNFAIP3 F127C Coding Variation in Greek Primary Sjogren's Syndrome Patients Periodontal disease peripheral blood mononuclear cell E_01_0309 PCR The TNFAIP3 gene encodes the A20 protein essential for the development and functional performance of dendritic, B and T cells and macrophages as well as an important negative feedback regulator of the NF-κB pathway Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The TNFAIP3 gene encodes the A20 protein essential for the development and functional performance of dendritic, B and T cells and macrophages as well as an important negative feedback regulator of the NF-κB pathway Immunohistochemical staining The TNFAIP3 gene encodes the A20 protein essential for the development and functional performance of dendritic, B and T cells and macrophages as well as an important negative feedback regulator of the NF-κB pathway PCR TNFAIP3 The TNFAIP3 gene encodes the A20 protein essential for the development and functional performance of dendritic, B and T cells and macrophages as well as an important negative feedback regulator of the NF-κB pathway 30662804 chr6 11180709 11182709 NEDD9 Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. human bladder High+Lowthroughput SPAG9 regulates HEF1 expression and drives EMT in bladder transitional cell carcinoma via rac1 signaling pathway Transitional cell carcinoma of the urinary bladder bladder cancer cell E_01_0310 PCR, Western blot, sequencing technology Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. Immunohistochemical staining Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. PCR，Western blot，测序技术 NEDD9 Human enhancer of filamentation 1 (HEF1, also known as CasL and NEDD9) is a non-catalytic scaffolding protein belonging to CAS (Crk-associated substrate) protein family that interacts with multiple signaling cascades. 30662285 chr11 102517572 102519572 MMP7 Notch3 may affect the invasiveness and metastasis of osteosarcoma cells by regulating the downstream target gene Hes1 and its effector protein, MMP7. human bone High+Lowthroughput Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients Osteosarcoma osteosarcoma cell E_01_0311 Lentiviral transfection, gene knockdown, PCR, Western blot Notch3 may affect the invasiveness and metastasis of osteosarcoma cells by regulating the downstream target gene Hes1 and its effector protein, MMP7. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Notch3 may affect the invasiveness and metastasis of osteosarcoma cells by regulating the downstream target gene Hes1 and its effector protein, MMP7. Immunohistochemical staining Notch3 may affect the invasiveness and metastasis of osteosarcoma cells by regulating the downstream target gene Hes1 and its effector protein, MMP7. 慢病毒转染，基因敲除，PCR，Western blot MMP7 Notch3 may affect the invasiveness and metastasis of osteosarcoma cells by regulating the downstream target gene Hes1 and its effector protein, MMP7. 30659980 chrX 154538337 154540337 IKBKG IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency. human bone High+Lowthroughput Absence of an osteopetrosis phenotype in IKBKG (NEMO) mutation-positive women: A case-control study Osteosclerosis B cell， Oc precursor cell E_01_0312 PCR，Bone marrow aspiration，Histomorphometry IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency. Immunohistochemical staining IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency. PCR，Bone marrow aspiration，Histomorphometry IKBKG IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency. 30659195 chr19 15232704 15234704 BRD4 Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers human liver High+Lowthroughput Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming liver cancer HCC cell E_01_0313 PCR，Western blot，ChIP-seq Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers Immunohistochemical staining Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers PCR，Western blot，ChIP-seq BRD4 Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers 30659153 chr16 67560054 67562054 CTCF chromHMM chromatin states from Roadmap (32), cross-tissue gene expression for TSSs from GTEx (33), TAD boundaries from high-resolution Hi-C data, called using an arrowhead score (34), and binding clusters for the insulator protein CTCF from ENCODE human High+Lowthroughput Chromatin features constrain structural variation across evolutionary timescales E_01_0314 Western blot，ChIP-seq chromHMM chromatin states from Roadmap (32), cross-tissue gene expression for TSSs from GTEx (33), TAD boundaries from high-resolution Hi-C data, called using an arrowhead score (34), and binding clusters for the insulator protein CTCF from ENCODE Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq chromHMM chromatin states from Roadmap (32), cross-tissue gene expression for TSSs from GTEx (33), TAD boundaries from high-resolution Hi-C data, called using an arrowhead score (34), and binding clusters for the insulator protein CTCF from ENCODE Immunohistochemical staining chromHMM chromatin states from Roadmap (32), cross-tissue gene expression for TSSs from GTEx (33), TAD boundaries from high-resolution Hi-C data, called using an arrowhead score (34), and binding clusters for the insulator protein CTCF from ENCODE Western blot，ChIP-seq CTCF chromHMM chromatin states from Roadmap (32), cross-tissue gene expression for TSSs from GTEx (33), TAD boundaries from high-resolution Hi-C data, called using an arrowhead score (34), and binding clusters for the insulator protein CTCF from ENCODE 30657937 chr16 85896547 85898547 IRF8 We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity human High+Lowthroughput NextPBM: a platform to study cell-specific transcription factor binding and cooperativity E_01_0315 HT nextPBM We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity Immunohistochemical staining We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity HT nextPBM IRF8 We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity 30655550 chr19 17400341 17402341 BST2 CBX6 induced significant downregulation of bone marrow stromal cell antigen-2 (BST2), a potential therapeutic target, via interactions with its promoter region. Our collective findings support a tumor suppressor role of CBX6 in breast cancer. human breast High+Lowthroughput CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer mammary cancer breast cancer cell E_01_0316 PCR，Western blot，ChIP-seq CBX6 induced significant downregulation of bone marrow stromal cell antigen-2 (BST2), a potential therapeutic target, via interactions with its promoter region. Our collective findings support a tumor suppressor role of CBX6 in breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CBX6 induced significant downregulation of bone marrow stromal cell antigen-2 (BST2), a potential therapeutic target, via interactions with its promoter region. Our collective findings support a tumor suppressor role of CBX6 in breast cancer. Immunohistochemical staining CBX6 induced significant downregulation of bone marrow stromal cell antigen-2 (BST2), a potential therapeutic target, via interactions with its promoter region. Our collective findings support a tumor suppressor role of CBX6 in breast cancer. PCR，Western blot，ChIP-seq BST2 CBX6 induced significant downregulation of bone marrow stromal cell antigen-2 (BST2), a potential therapeutic target, via interactions with its promoter region. Our collective findings support a tumor suppressor role of CBX6 in breast cancer. 30655376 chr14 68785051 68787051 ZFP36L1 In vitro reporter assay and 5'-azacitidine treatment confirmed the functional relevance of hyper-methylation of ZFP36L1 enhancer. human bone High+Lowthroughput Epigenomic profiling of myelofibrosis reveals widespread DNA methylation changes in enhancer elements and ZFP36L1 as a potential tumor suppressor gene that is epigenetically regulated Myelofibrosis bone marrow cell E_01_0317 PCR，Western blot In vitro reporter assay and 5'-azacitidine treatment confirmed the functional relevance of hyper-methylation of ZFP36L1 enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In vitro reporter assay and 5'-azacitidine treatment confirmed the functional relevance of hyper-methylation of ZFP36L1 enhancer. Immunohistochemical staining In vitro reporter assay and 5'-azacitidine treatment confirmed the functional relevance of hyper-methylation of ZFP36L1 enhancer. PCR，Western blot ZFP36L1 In vitro reporter assay and 5'-azacitidine treatment confirmed the functional relevance of hyper-methylation of ZFP36L1 enhancer. 30654703 chr12 57092847 57094847 STAT6 The overexpression vectors of NEAT1 and ITCH, and siRNA targeting NEAT1, EZH2 (enhancer of zeste homolog 2) and STAT6 (signal transducer and activator of transcription 6) were transfected into CD4+T cells. human lymph High+Lowthroughput NEAT1 regulates Th2 cell development by targeting STAT6 for degradation Th2 cell E_01_0318 PCR, Western blot, chip SEQ, RNA immunoprecipitation, cell transfection The overexpression vectors of NEAT1 and ITCH, and siRNA targeting NEAT1, EZH2 (enhancer of zeste homolog 2) and STAT6 (signal transducer and activator of transcription 6) were transfected into CD4+T cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The overexpression vectors of NEAT1 and ITCH, and siRNA targeting NEAT1, EZH2 (enhancer of zeste homolog 2) and STAT6 (signal transducer and activator of transcription 6) were transfected into CD4+T cells. Immunohistochemical staining The overexpression vectors of NEAT1 and ITCH, and siRNA targeting NEAT1, EZH2 (enhancer of zeste homolog 2) and STAT6 (signal transducer and activator of transcription 6) were transfected into CD4+T cells. PCR，Western blot，ChIP-seq，RNA免疫沉淀，细胞转染 STAT6 The overexpression vectors of NEAT1 and ITCH, and siRNA targeting NEAT1, EZH2 (enhancer of zeste homolog 2) and STAT6 (signal transducer and activator of transcription 6) were transfected into CD4+T cells. 30653446 chr3 11269697 11271697 ATG7 Specifically, deletion of ATG7 in retinal vascular ECs of db/db mice and cultured HUVECs indicated a detrimental role of autophagy in hyperglycemia-induced endothelial dysfunction. Pretreatment with GANT61, a Hh pathway inhibitor, abolished the metformin-mediated downregulation of autophagy and endothelial protective action human kidney High+Lowthroughput Metformin alleviates hyperglycemia-induced endothelial impairment by downregulating autophagy via the Hedgehog pathway diabetes endothelial cell E_01_0319 PCR Specifically, deletion of ATG7 in retinal vascular ECs of db/db mice and cultured HUVECs indicated a detrimental role of autophagy in hyperglycemia-induced endothelial dysfunction. Pretreatment with GANT61, a Hh pathway inhibitor, abolished the metformin-mediated downregulation of autophagy and endothelial protective action Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Specifically, deletion of ATG7 in retinal vascular ECs of db/db mice and cultured HUVECs indicated a detrimental role of autophagy in hyperglycemia-induced endothelial dysfunction. Pretreatment with GANT61, a Hh pathway inhibitor, abolished the metformin-mediated downregulation of autophagy and endothelial protective action Immunohistochemical staining Specifically, deletion of ATG7 in retinal vascular ECs of db/db mice and cultured HUVECs indicated a detrimental role of autophagy in hyperglycemia-induced endothelial dysfunction. Pretreatment with GANT61, a Hh pathway inhibitor, abolished the metformin-mediated downregulation of autophagy and endothelial protective action PCR ATG7,BNIP3 Specifically, deletion of ATG7 in retinal vascular ECs of db/db mice and cultured HUVECs indicated a detrimental role of autophagy in hyperglycemia-induced endothelial dysfunction. Pretreatment with GANT61, a Hh pathway inhibitor, abolished the metformin-mediated downregulation of autophagy and endothelial protective action;Mechanistically, GLI1 knockdown-triggered autophagy was related to upregulation of BNIP3, which subsequently disrupted the association of BECN1/Beclin 1 and BCL2. 30651971 chr9 117701165 117703165 TLR4 Furthermore, defciency of TLR4 receptor resulted in disappeared of the autophagy activation by treatment with IL-33 or EBSS (Fig. 6). human lymph High+Lowthroughput IL-33 ameliorates experimental colitis involving regulation of autophagy of macrophages in mice colitis macrophage E_01_0320 Western blot, immunofluorescence staining Furthermore, defciency of TLR4 receptor resulted in disappeared of the autophagy activation by treatment with IL-33 or EBSS (Fig. 6). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, defciency of TLR4 receptor resulted in disappeared of the autophagy activation by treatment with IL-33 or EBSS (Fig. 6). Immunohistochemical staining Furthermore, defciency of TLR4 receptor resulted in disappeared of the autophagy activation by treatment with IL-33 or EBSS (Fig. 6). Western blot，免疫荧光染色法 TLR4 Furthermore, defciency of TLR4 receptor resulted in disappeared of the autophagy activation by treatment with IL-33 or EBSS (Fig. 6). 30651597 chr3 69736856 69738856 MITF Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. human kidney High+Lowthroughput Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair Renal cell E_01_0321 PCR, Western blot, chip SEQ, lentiviral infection, Clontech Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. Immunohistochemical staining Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. PCR，Western blot，ChIP-seq，慢病毒感染，克隆技术 CDK7 MITF,MYC Moreover, MITF controls cMYC implicated in general transcription by transactivation of far upstream binding protein 2 (FUBP2/KSHRP), which induces c-MYC pulse regulation through TFIIH, and experimental depletion of MITF results in consecutive loss of CDK7 in the TFIIH-CAK subcomplex Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo.;Moreover, MITF controls cMYC implicated in general transcription by transactivation of far upstream binding protein 2 (FUBP2/KSHRP), which induces c-MYC pulse regulation through TFIIH, and experimental depletion of MITF results in consecutive loss of CDK7 in the TFIIH-CAK subcomplex 30649550 chr2 86437792 86439792 KDM3A In the current study, using a FBSinducing model following serum starvation, we identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes. human lymph High+Lowthroughput Histone demethylase KDM3A is required for enhancer activation of hippo target genes in colorectal cancer colorectal cancer HCT116 cell E_01_0322 PCR，Western blot，ChIP-seq In the current study, using a FBSinducing model following serum starvation, we identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the current study, using a FBSinducing model following serum starvation, we identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes. Immunohistochemical staining In the current study, using a FBSinducing model following serum starvation, we identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes. PCR，Western blot，ChIP-seq KDM3A In the current study, using a FBSinducing model following serum starvation, we identified KDM3A, a demethylase of histone H3K9me1/2, as a positive regulator for hippo target genes. 30644437 chr22 30922640 30924640 MORC2 Here, we found that MORC2 interacted with TE-III domain of C/EBPα, and the overexpression of MORC2 promoted wild-type C/EBPα sumoylation and its subsequent degradation, which didn’t significantly observe in mutant C/EBPα-K161R. human lymph High+Lowthroughput MORC2 regulates C/EBPα-mediated cell differentiation via sumoylation C2C12 cell E_01_0323 PCR，Western blot Here, we found that MORC2 interacted with TE-III domain of C/EBPα, and the overexpression of MORC2 promoted wild-type C/EBPα sumoylation and its subsequent degradation, which didn’t significantly observe in mutant C/EBPα-K161R. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we found that MORC2 interacted with TE-III domain of C/EBPα, and the overexpression of MORC2 promoted wild-type C/EBPα sumoylation and its subsequent degradation, which didn’t significantly observe in mutant C/EBPα-K161R. Immunohistochemical staining Here, we found that MORC2 interacted with TE-III domain of C/EBPα, and the overexpression of MORC2 promoted wild-type C/EBPα sumoylation and its subsequent degradation, which didn’t significantly observe in mutant C/EBPα-K161R. PCR，Western blot MORC2 Here, we found that MORC2 interacted with TE-III domain of C/EBPα, and the overexpression of MORC2 promoted wild-type C/EBPα sumoylation and its subsequent degradation, which didn’t significantly observe in mutant C/EBPα-K161R. 30643424 chr17 42310283 42312283 STAT3 Zhang et al’s29 research showed that pancreatic cancer stem cells developed chemoresistance toward GEM through the NAPDH oxidase/ROS (Nox/ROS)/NF-κB/STAT 3 signaling pathway (STAT3). human tongue High+Lowthroughput Evodiamine inactivates NF-κB and potentiates the antitumor effects of gemcitabine on tongue cancer both in vitro and in vivo tongue cancer tongue cancer cell，Tca8113 cell E_01_0324 PCR, sequencing technology Zhang et al’s29 research showed that pancreatic cancer stem cells developed chemoresistance toward GEM through the NAPDH oxidase/ROS (Nox/ROS)/NF-κB/STAT 3 signaling pathway (STAT3). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Zhang et al’s29 research showed that pancreatic cancer stem cells developed chemoresistance toward GEM through the NAPDH oxidase/ROS (Nox/ROS)/NF-κB/STAT 3 signaling pathway (STAT3). Immunohistochemical staining Zhang et al’s29 research showed that pancreatic cancer stem cells developed chemoresistance toward GEM through the NAPDH oxidase/ROS (Nox/ROS)/NF-κB/STAT 3 signaling pathway (STAT3). PCR，测序技术 STAT3 Zhang et al’s29 research showed that pancreatic cancer stem cells developed chemoresistance toward GEM through the NAPDH oxidase/ROS (Nox/ROS)/NF-κB/STAT 3 signaling pathway (STAT3). 30642336 chr18 76976527 76978527 MBP ScFv antibody proteins without any tag and with different fusion tags such as 6xHis, GST and MBP, were expressed in E. coli in diferent growth condition. human lymph High+Lowthroughput Evaluation of scFv protein recovery from E. coli by in vitro refolding and mild solubilization process E_01_0325 In vitro refolding and gentle lysis method ScFv antibody proteins without any tag and with different fusion tags such as 6xHis, GST and MBP, were expressed in E. coli in diferent growth condition. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ScFv antibody proteins without any tag and with different fusion tags such as 6xHis, GST and MBP, were expressed in E. coli in diferent growth condition. Immunohistochemical staining ScFv antibody proteins without any tag and with different fusion tags such as 6xHis, GST and MBP, were expressed in E. coli in diferent growth condition. 体外重折叠和温和溶解法 MBP ScFv antibody proteins without any tag and with different fusion tags such as 6xHis, GST and MBP, were expressed in E. coli in diferent growth condition. 30642251 chr17 7658541 7660541 TP53 If gene symbols are used that do not occur in the downloaded annotation data, as can be the case if an invalid or outdated symbol is used (e.g., P53 instead of the official gene symbol TP53), GOPHER will issue a warning and report a list of unmappable symbols that can be used to search for the current correct symbols. human adipose High+Lowthroughput GOPHER: Generator Of Probes for capture Hi-C Experiments at high Resolution IWAT cell E_01_0326 Hi-C，PCR，Western blot，ChIP-seq If gene symbols are used that do not occur in the downloaded annotation data, as can be the case if an invalid or outdated symbol is used (e.g., P53 instead of the official gene symbol TP53), GOPHER will issue a warning and report a list of unmappable symbols that can be used to search for the current correct symbols. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq If gene symbols are used that do not occur in the downloaded annotation data, as can be the case if an invalid or outdated symbol is used (e.g., P53 instead of the official gene symbol TP53), GOPHER will issue a warning and report a list of unmappable symbols that can be used to search for the current correct symbols. Immunohistochemical staining If gene symbols are used that do not occur in the downloaded annotation data, as can be the case if an invalid or outdated symbol is used (e.g., P53 instead of the official gene symbol TP53), GOPHER will issue a warning and report a list of unmappable symbols that can be used to search for the current correct symbols. Hi-C，PCR，Western blot，ChIP-seq TP53 If gene symbols are used that do not occur in the downloaded annotation data, as can be the case if an invalid or outdated symbol is used (e.g., P53 instead of the official gene symbol TP53), GOPHER will issue a warning and report a list of unmappable symbols that can be used to search for the current correct symbols. 30639323 chr16 86507633 86509633 FOXF1 In contrast to ACDMPV caused by loss-of-function (LoF) of FOXF1 (MIM: 601089),20,21 the molecular etiology of AcDys and CAD is largely unknown. human Lung High+Lowthroughput Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway Pulmonary hypoplasia IMR-90 ，NHLF cell E_01_0327 PCR, chip SEQ, variant enrichment analysis, bioinformatics prediction In contrast to ACDMPV caused by loss-of-function (LoF) of FOXF1 (MIM: 601089),20,21 the molecular etiology of AcDys and CAD is largely unknown. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In contrast to ACDMPV caused by loss-of-function (LoF) of FOXF1 (MIM: 601089),20,21 the molecular etiology of AcDys and CAD is largely unknown. Immunohistochemical staining In contrast to ACDMPV caused by loss-of-function (LoF) of FOXF1 (MIM: 601089),20,21 the molecular etiology of AcDys and CAD is largely unknown. PCR，ChIP-seq，变体富集分析，生物信息学预测 FOXF1 In contrast to ACDMPV caused by loss-of-function (LoF) of FOXF1 (MIM: 601089),20,21 the molecular etiology of AcDys and CAD is largely unknown. 30632221 chr8 127732390 127734390 MYC MYC is known to cause increased expression of EZH2 in prostate cancer, both directly and through downregulation of miR-26a and miR-26b, which are known to inhibit EZH2.5 human brain High+Lowthroughput Inhibition of enhancer of zest homologue 2 is a potential therapeutic target for high-MYC medulloblastoma Medulloblastoma E_01_0328 PCR，Western blot MYC is known to cause increased expression of EZH2 in prostate cancer, both directly and through downregulation of miR-26a and miR-26b, which are known to inhibit EZH2.5 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MYC is known to cause increased expression of EZH2 in prostate cancer, both directly and through downregulation of miR-26a and miR-26b, which are known to inhibit EZH2.5 Immunohistochemical staining MYC is known to cause increased expression of EZH2 in prostate cancer, both directly and through downregulation of miR-26a and miR-26b, which are known to inhibit EZH2.5 PCR，Western blot MYC,EZH2 MYC is known to cause increased expression of EZH2 in prostate cancer, both directly and through downregulation of miR-26a and miR-26b, which are known to inhibit EZH2.5;MYC is known to cause increased expression of EZH2 in prostate cancer, both directly and through downregulation of miR-26a and miR-26b, which are known to inhibit EZH2.5 30631044 chr13 27957842 27959842 CDX2 Caudal-related homeobox transcription factor 2 (CDX2), an intestine-specific nuclear transcription factor, has been strongly implicated in the tumourigenesis of various human cancers. human lymph High+Lowthroughput CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/β-catenin signaling via transactivation of GSK-3β and Axin2 expression Colon cancer colon cancer cell E_01_0329 Immunohistochemistry, PCR, Western blot, chip seq Caudal-related homeobox transcription factor 2 (CDX2), an intestine-specific nuclear transcription factor, has been strongly implicated in the tumourigenesis of various human cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Caudal-related homeobox transcription factor 2 (CDX2), an intestine-specific nuclear transcription factor, has been strongly implicated in the tumourigenesis of various human cancers. Immunohistochemical staining Caudal-related homeobox transcription factor 2 (CDX2), an intestine-specific nuclear transcription factor, has been strongly implicated in the tumourigenesis of various human cancers. 免疫组化检测，PCR，Western blot，ChIP-seq CDX2 Caudal-related homeobox transcription factor 2 (CDX2), an intestine-specific nuclear transcription factor, has been strongly implicated in the tumourigenesis of various human cancers. 30628724 chr7 148804584 148806584 EZH2 Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. human prostate High+Lowthroughput Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer prostatic cancer Cancer Stem Cell E_01_0330 Immunoprecipitation, RNA SEQ, PCR, Western blot Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. Immunohistochemical staining Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. 免疫沉淀法，RNA-seq，PCR，Western blot EZH2 Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. 30628655 chr11 1155242 1157242 MUC5AC P300 decreases the protein expression level of MUC5AC. The empty vector, untransfected control, the P300 expression plasmid and P300 siRNA, together with their control plasmids, were transfected into A549 cells. Immunofluorescence was then performed to detect the protein expression of MUC5AC in each group. human Lung High+Lowthroughput Characterization of the human mucin 5AC promoter and its regulation by the histone acetyltransferase P300 asthma A549 cell E_01_0331 Transient transfection, luciferase assay, immunoprecipitation, PCR, Western blot P300 decreases the protein expression level of MUC5AC. The empty vector, untransfected control, the P300 expression plasmid and P300 siRNA, together with their control plasmids, were transfected into A549 cells. Immunofluorescence was then performed to detect the protein expression of MUC5AC in each group. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq P300 decreases the protein expression level of MUC5AC. The empty vector, untransfected control, the P300 expression plasmid and P300 siRNA, together with their control plasmids, were transfected into A549 cells. Immunofluorescence was then performed to detect the protein expression of MUC5AC in each group. Immunohistochemical staining P300 decreases the protein expression level of MUC5AC. The empty vector, untransfected control, the P300 expression plasmid and P300 siRNA, together with their control plasmids, were transfected into A549 cells. Immunofluorescence was then performed to detect the protein expression of MUC5AC in each group. 瞬时转染，荧光素酶检测，免疫沉淀法，PCR，Western blot MUC5AC P300 decreases the protein expression level of MUC5AC. The empty vector, untransfected control, the P300 expression plasmid and P300 siRNA, together with their control plasmids, were transfected into A549 cells. Immunofluorescence was then performed to detect the protein expression of MUC5AC in each group. 30626398 chr17 48604528 48606528 HOXB7 Finally, we performed both technical and experimental bisulfte pyrosequencing validations of three of the CpGs found at the HOXB7 (cg07547765), SOCS3 (cg11047325) and ZFPM2 (cg03830443) genes (Fig. 5, see Additional fle 13: Table S7 for full data). human blood High+Lowthroughput Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes E_01_0332 Bisulfite pyrosequencing Finally, we performed both technical and experimental bisulfte pyrosequencing validations of three of the CpGs found at the HOXB7 (cg07547765), SOCS3 (cg11047325) and ZFPM2 (cg03830443) genes (Fig. 5, see Additional fle 13: Table S7 for full data). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, we performed both technical and experimental bisulfte pyrosequencing validations of three of the CpGs found at the HOXB7 (cg07547765), SOCS3 (cg11047325) and ZFPM2 (cg03830443) genes (Fig. 5, see Additional fle 13: Table S7 for full data). Immunohistochemical staining Finally, we performed both technical and experimental bisulfte pyrosequencing validations of three of the CpGs found at the HOXB7 (cg07547765), SOCS3 (cg11047325) and ZFPM2 (cg03830443) genes (Fig. 5, see Additional fle 13: Table S7 for full data). 亚硫酸氢盐焦磷酸测序 HOXB7 Finally, we performed both technical and experimental bisulfte pyrosequencing validations of three of the CpGs found at the HOXB7 (cg07547765), SOCS3 (cg11047325) and ZFPM2 (cg03830443) genes (Fig. 5, see Additional fle 13: Table S7 for full data). 30622230 chr12 95513693 95515693 USP44 Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. human prostate High+Lowthroughput USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization prostatic cancer prostate cancer cell E_01_0333 PCR, immunofluorescence staining Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. Immunohistochemical staining Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. PCR，免疫荧光染色法 USP44 Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. 30621608 chr3 190319460 190321460 CLDN16 This rare disease is caused by mutations in CLDN16 that encodes claudin-16, a tight-junction protein involved in paracellular reabsorption of magnesium and calcium in the renal tubule. Most of these variants are located in exons and have been classified as missense mutations. human kidney High+Lowthroughput Exonic CLDN16 mutations associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis can induce deleterious mRNA alterations Familial hypomagnesemia, hypercalciuria, and nephrocalcinosis COS7 cells E_01_0334 PCR This rare disease is caused by mutations in CLDN16 that encodes claudin-16, a tight-junction protein involved in paracellular reabsorption of magnesium and calcium in the renal tubule. Most of these variants are located in exons and have been classified as missense mutations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This rare disease is caused by mutations in CLDN16 that encodes claudin-16, a tight-junction protein involved in paracellular reabsorption of magnesium and calcium in the renal tubule. Most of these variants are located in exons and have been classified as missense mutations. Immunohistochemical staining This rare disease is caused by mutations in CLDN16 that encodes claudin-16, a tight-junction protein involved in paracellular reabsorption of magnesium and calcium in the renal tubule. Most of these variants are located in exons and have been classified as missense mutations. PCR CLDN16 This rare disease is caused by mutations in CLDN16 that encodes claudin-16, a tight-junction protein involved in paracellular reabsorption of magnesium and calcium in the renal tubule. Most of these variants are located in exons and have been classified as missense mutations. 30620726 chr3 128476298 128478298 GATA2 GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. human blood High+Lowthroughput Single-nucleotide human disease mutation inactivates a blood-regenerative GATA2 enhancer Acute myeloid leukemia progenitor cell E_01_0335 PCR，ChIP-seq GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. Immunohistochemical staining GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. PCR，ChIP-seq GATA2 GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. 30619471 chr17 42310619 42312619 STAT3 As a proof of concept of a possible functional relevance of this observation, we experimentally verified that the expression levels of a circRNA derived from an MS-associated locus, i.e., hsa_circ_0043813 from the STAT3 gene, can be modulated by the three genotypes at the disease-associated SNP. human nerve High+Lowthroughput Interpreting Non-coding Genetic Variation in Multiple Sclerosis Genome-Wide Associated Regions Multiple sclerosis SH-SY5Y， Jurkat cell E_01_0336 RNA sequencing, PCR As a proof of concept of a possible functional relevance of this observation, we experimentally verified that the expression levels of a circRNA derived from an MS-associated locus, i.e., hsa_circ_0043813 from the STAT3 gene, can be modulated by the three genotypes at the disease-associated SNP. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As a proof of concept of a possible functional relevance of this observation, we experimentally verified that the expression levels of a circRNA derived from an MS-associated locus, i.e., hsa_circ_0043813 from the STAT3 gene, can be modulated by the three genotypes at the disease-associated SNP. Immunohistochemical staining As a proof of concept of a possible functional relevance of this observation, we experimentally verified that the expression levels of a circRNA derived from an MS-associated locus, i.e., hsa_circ_0043813 from the STAT3 gene, can be modulated by the three genotypes at the disease-associated SNP. RNA测序，PCR STAT3 As a proof of concept of a possible functional relevance of this observation, we experimentally verified that the expression levels of a circRNA derived from an MS-associated locus, i.e., hsa_circ_0043813 from the STAT3 gene, can be modulated by the three genotypes at the disease-associated SNP. 30618413 chr4 153681347 153683347 TLR2 Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65) human prostate High+Lowthroughput Toll-like receptor 10 (TLR10) exhibits suppressive effects on inflammation of prostate epithelial cells prostatitis prostate epithelial cell E_01_0337 PCR，Western blot，ChIP-seq Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65) Immunohistochemical staining Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65) PCR，Western blot，ChIP-seq TLR2 Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65) 30610059 chr10 70594223 70596223 PRF1 H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. human colorectum High+Lowthroughput SUV39H1 Represses the Expression of Cytotoxic T-Lymphocyte Effector Genes to Promote Colon Tumor Immune Evasion Colon neoplasms T cell E_01_0338 Immunohistochemical staining, flow cytometry, PCR, Western blot, chip seq H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. Immunohistochemical staining H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. 免疫组织化学染色法，流式细胞术，PCR，Western blot，ChIP-seq ZNF395 H3K9me3 was enriched in the promoters of GZMB, PRF1, FASLG, and IFNG in quiescent T cells. 30606720 chr3 181709342 181711342 SOX2 In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer human breast High+Lowthroughput SIX2 Mediates Late-Stage Metastasis via Direct Regulation of SOX2 and Induction of a Cancer Stem Cell Program mammary cancer Cancer Stem Cell E_01_0339 PCR，Western blot，RNA-seq In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer Immunohistochemical staining In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer PCR，Western blot，RNA-seq SOX2 In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer 30605688 chr2 69455371 69457371 AAK1 Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer human High+Lowthroughput WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop HEK293T E_01_0340 PCR，Western blot Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer Immunohistochemical staining Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer PCR，Western blot AAK1 Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer 30603559 chr7 148804645 148806645 EZH2 Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2) human Hair High+Lowthroughput MiR-214 Regulates the Human Hair Follicle Stem Cell Proliferation and Differentiation by Targeting EZH2 and Wnt/β-Catenin Signaling Way In Vitro Hair Follicle Stem Cell E_01_0341 Immunofluorescence, DAPI staining, PCR Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2) Immunohistochemical staining Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2) 免疫荧光法，DAPI染色，PCR EZH2 Western blot determined the expression levels of enhancer of zeste homolog 2 (EZH2) 30596070 chr19 10130616 10132616 DNMT1 Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). human Lung High+Lowthroughput H3K27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the lncRNA HOTAIR lung cancer NSCLC cell E_01_0342 Flow cytometry, cell transfection techniques, immunohistochemical staining, PCR, Western blot, chip seq Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). Immunohistochemical staining Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). 流式细胞术，细胞转染技术，免疫组织化学染色，PCR，Western blot，ChIP-seq DNMT1 Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). 30594152 chr22 37967907 37969907 SOX10 Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. human nerve High+Lowthroughput Characterization and functional analyses of the human HTR1A gene: 5' regulatory region modulates gene expression in vitro Schizophrenia SK-N-SH cell E_01_0343 Cell transfection Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. Immunohistochemical staining Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. 细胞转染 SOX10 Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. 30590588 chr2 144361789 144363789 ZEB2 The spatiotemporal regulation of ZEB2 is complex and involves various regulatory elements, including alternative promoters and specific enhancers that contribute to the multifactorial function of this transcription factor human nerve High+Lowthroughput Functional characterization of the ZEB2 regulatory landscape neural crest cell E_01_0344 Hi-C，PCR，Western blot，ChIP-seq The spatiotemporal regulation of ZEB2 is complex and involves various regulatory elements, including alternative promoters and specific enhancers that contribute to the multifactorial function of this transcription factor Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The spatiotemporal regulation of ZEB2 is complex and involves various regulatory elements, including alternative promoters and specific enhancers that contribute to the multifactorial function of this transcription factor Immunohistochemical staining The spatiotemporal regulation of ZEB2 is complex and involves various regulatory elements, including alternative promoters and specific enhancers that contribute to the multifactorial function of this transcription factor Hi-C，PCR，Western blot，ChIP-seq ZEB2 The spatiotemporal regulation of ZEB2 is complex and involves various regulatory elements, including alternative promoters and specific enhancers that contribute to the multifactorial function of this transcription factor 30590042 chr20 33672756 33674756 E2F1 We found that the transcription factor E2F1 and its heterodimerization partner DP1 represent a dependency in multiple myeloma cells. human bone High+Lowthroughput Non-overlapping Control of Transcriptome by Promoter- and Super-Enhancer-Associated Dependencies in Multiple Myeloma Multiple myeloma multiple myeloma cell E_01_0345 PCR，Western blot，ChIP-seq We found that the transcription factor E2F1 and its heterodimerization partner DP1 represent a dependency in multiple myeloma cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that the transcription factor E2F1 and its heterodimerization partner DP1 represent a dependency in multiple myeloma cells. Immunohistochemical staining We found that the transcription factor E2F1 and its heterodimerization partner DP1 represent a dependency in multiple myeloma cells. PCR，Western blot，ChIP-seq E2F1 We found that the transcription factor E2F1 and its heterodimerization partner DP1 represent a dependency in multiple myeloma cells. 30563971 chr3 189628751 189630751 TP63 We further identified that the TP63 gene was repressed by this precision-guided machinery of TRPS1-CHD4/NuRD(MTA2) complex, which decommissions its enhancer leading to a decrease in ΔNp63 and enhancing the metastatic ability of breast cancer cells. human breast High+Lowthroughput Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression mammary cancer T47D cell E_01_0346 PCR，Western blot，ChIP-seq We further identified that the TP63 gene was repressed by this precision-guided machinery of TRPS1-CHD4/NuRD(MTA2) complex, which decommissions its enhancer leading to a decrease in ΔNp63 and enhancing the metastatic ability of breast cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We further identified that the TP63 gene was repressed by this precision-guided machinery of TRPS1-CHD4/NuRD(MTA2) complex, which decommissions its enhancer leading to a decrease in ΔNp63 and enhancing the metastatic ability of breast cancer cells. Immunohistochemical staining We further identified that the TP63 gene was repressed by this precision-guided machinery of TRPS1-CHD4/NuRD(MTA2) complex, which decommissions its enhancer leading to a decrease in ΔNp63 and enhancing the metastatic ability of breast cancer cells. PCR，Western blot，ChIP-seq TP63 We further identified that the TP63 gene was repressed by this precision-guided machinery of TRPS1-CHD4/NuRD(MTA2) complex, which decommissions its enhancer leading to a decrease in ΔNp63 and enhancing the metastatic ability of breast cancer cells. 30559760 chr7 151553558 151555558 PRKAG2 we analyzed a whole genome case-control expression profiles in human CKD to investigate whether the susceptibility gene PRKAG2 is differently expressed in CKD cases compared with control samples. human kidney High+Lowthroughput Functional Prediction of Chronic Kidney Disease Susceptibility Gene PRKAG2 by Comprehensively Bioinformatics Analysis Chronic kidney disease Caco2 cell E_01_0347 ChIP-seq we analyzed a whole genome case-control expression profiles in human CKD to investigate whether the susceptibility gene PRKAG2 is differently expressed in CKD cases compared with control samples. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq we analyzed a whole genome case-control expression profiles in human CKD to investigate whether the susceptibility gene PRKAG2 is differently expressed in CKD cases compared with control samples. Immunohistochemical staining we analyzed a whole genome case-control expression profiles in human CKD to investigate whether the susceptibility gene PRKAG2 is differently expressed in CKD cases compared with control samples. ChIP-seq PRKAG2 we analyzed a whole genome case-control expression profiles in human CKD to investigate whether the susceptibility gene PRKAG2 is differently expressed in CKD cases compared with control samples. 30552336 chr17 72118256 72120256 SOX9 In a recent independent but complementary study on Sox9 regulation in the mouse by Gonen and colleagues, an orthologous mouse enhancer (Enh13) showing 80% sequence conservation with eSR-A was identified13 . human epithelial High+Lowthroughput Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9 COS7 cells E_01_0348 PCR，ChIP-seq In a recent independent but complementary study on Sox9 regulation in the mouse by Gonen and colleagues, an orthologous mouse enhancer (Enh13) showing 80% sequence conservation with eSR-A was identified13 . Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In a recent independent but complementary study on Sox9 regulation in the mouse by Gonen and colleagues, an orthologous mouse enhancer (Enh13) showing 80% sequence conservation with eSR-A was identified13 . Immunohistochemical staining In a recent independent but complementary study on Sox9 regulation in the mouse by Gonen and colleagues, an orthologous mouse enhancer (Enh13) showing 80% sequence conservation with eSR-A was identified13 . PCR，ChIP-seq SOX9 In a recent independent but complementary study on Sox9 regulation in the mouse by Gonen and colleagues, an orthologous mouse enhancer (Enh13) showing 80% sequence conservation with eSR-A was identified13 . 30544224 chr14 73133812 73135812 PSEN1 Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. human lymph High+Lowthroughput Analysis of hidradenitis suppurativa-linked mutations in four genes and the effects of PSEN1-P242LfsX11 on cytokine and chemokine expression in macrophages Hidradenitis suppurativa THP-1 cells E_01_0349 PCR，Western blot Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. Immunohistochemical staining Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. PCR，Western blot PSEN1 Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. 30538561 chr7 100799729 100801729 EPHB4 We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. human colorectum High+Lowthroughput Notch signaling promotes serrated neoplasia pathway in colorectal cancer through epigenetic modification of EPHB2 and EPHB4 colorectal cancer SW620 cell E_01_0350 PCR, Western blot, chip SEQ, immunoblotting We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. Immunohistochemical staining We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. PCR，Western blot，ChIP-seq，免疫印迹法 EPHB4 We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. 30531861 chr4 121814031 121816031 CCNA2 Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. human liver High+Lowthroughput Cyclin A2/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress Hepatocellular carcinoma E_01_0351 PCR，Western blot，ChIP-seq Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. Immunohistochemical staining Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. PCR，Western blot，ChIP-seq CCNA2 Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. 30529831 chr6 84684707 84686707 TBX18 Our analyses also suggest a role in atherosclerosis for developmental transcription factor genes having little or no previous association with atherosclerosis, such as NR2F2 (COUP-TFII) and TBX18. human blood High+Lowthroughput Atherosclerosis-associated differentially methylated regions can reflect the disease phenotype and are often at enhancers atherosclerosis E_01_0352 Differentially methylated region method Our analyses also suggest a role in atherosclerosis for developmental transcription factor genes having little or no previous association with atherosclerosis, such as NR2F2 (COUP-TFII) and TBX18. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our analyses also suggest a role in atherosclerosis for developmental transcription factor genes having little or no previous association with atherosclerosis, such as NR2F2 (COUP-TFII) and TBX18. Immunohistochemical staining Our analyses also suggest a role in atherosclerosis for developmental transcription factor genes having little or no previous association with atherosclerosis, such as NR2F2 (COUP-TFII) and TBX18. 差异甲基化区域法 TBX18 Our analyses also suggest a role in atherosclerosis for developmental transcription factor genes having little or no previous association with atherosclerosis, such as NR2F2 (COUP-TFII) and TBX18. 30975980 chr7 19018300 19020300 TWIST1 SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. human Epithelial High+Lowthroughput Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression 否 Epithelial ovarian carcinoma E_01_0353 Gene knockdown, cell transfection techniques, Western blot SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. Immunohistochemical staining SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. 基因敲降、细胞转染技术、Western blot TWIST2 TWIST1 SC66 also attenuated expression of TWIST1 and Mcl-2, factors important in cell invasiveness and anti-apoptosis, respectively. SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. 30970615 chr4 41253337 41255337 UCHL1 UCHL1 was associated with growth breast cancer [61]. The loss of tumor suppressor UCHL1 was responsible for the inactivation of apoptosis, as well as cisplatin resistance, in EOC human High+Lowthroughput Mining Featured Biomarkers Linked with Epithelial Ovarian CancerBased on Bioinformatics 否 Epithelial Ovarian CancerBased ovarian cell E_01_0354 Immunofluorescence staining UCHL1 was associated with growth breast cancer [61]. The loss of tumor suppressor UCHL1 was responsible for the inactivation of apoptosis, as well as cisplatin resistance, in EOC Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq UCHL1 was associated with growth breast cancer [61]. The loss of tumor suppressor UCHL1 was responsible for the inactivation of apoptosis, as well as cisplatin resistance, in EOC Immunohistochemical staining UCHL1 was associated with growth breast cancer [61]. The loss of tumor suppressor UCHL1 was responsible for the inactivation of apoptosis, as well as cisplatin resistance, in EOC 免疫荧光染色 UCHL1 UCHL1 was associated with growth breast cancer [61]. The loss of tumor suppressor UCHL1 was responsible for the inactivation of apoptosis, as well as cisplatin resistance, in EOC 30967505 chr7 148804534 148806534 EZH2 Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). human Ovarian High+Lowthroughput Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase 否 cancer E_01_0355 gel electrophoresis Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). Immunohistochemical staining Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). 凝胶电泳 EZH2 Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). 30955885 chr16 67559978 67561978 CTCF Uncoupling DNA demethylation from antisense transcription by Tet3 overexpression in mouse olfactory neurons promotes CTCF binding to all Pcdhα promoters, resulting in proximity-biased DNA looping of the HS5-1 enhancer. human epithelial cells High+Lowthroughput Antisense lncRNA Transcription Mediates DNA Demethylation to Drive Stochastic Protocadherin α Promoter Choice 否 E_01_0356 Immunofluorescence staining Uncoupling DNA demethylation from antisense transcription by Tet3 overexpression in mouse olfactory neurons promotes CTCF binding to all Pcdhα promoters, resulting in proximity-biased DNA looping of the HS5-1 enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Uncoupling DNA demethylation from antisense transcription by Tet3 overexpression in mouse olfactory neurons promotes CTCF binding to all Pcdhα promoters, resulting in proximity-biased DNA looping of the HS5-1 enhancer. Immunohistochemical staining Uncoupling DNA demethylation from antisense transcription by Tet3 overexpression in mouse olfactory neurons promotes CTCF binding to all Pcdhα promoters, resulting in proximity-biased DNA looping of the HS5-1 enhancer. 免疫荧光染色 CTCF Uncoupling DNA demethylation from antisense transcription by Tet3 overexpression in mouse olfactory neurons promotes CTCF binding to all Pcdhα promoters, resulting in proximity-biased DNA looping of the HS5-1 enhancer. 30952976 chr3 194133551 194135551 HES1 We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. human High+Lowthroughput O-GlcNAc Transferase Inhibition Differentially Affects Breast Cancer Subtypes 否 Affects Breast Cancer E_01_0357 Western blot, gene knockdown We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. Immunohistochemical staining We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. Western blot、基因敲降 HES1 We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. 30948729 chr1 27662995 27664995 IFI6 Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. human Epithelial High+Lowthroughput An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis 否 E_01_0358 QRT PCR, Western blot, immunofluorescence staining, gel electrophoresis, chip SEQ, RNA seq Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. Immunohistochemical staining Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. qRT-PCR、Western blot、免疫荧光染色、凝胶电泳、ChIP-seq、RNA-seq IFI6 Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression. 30945396 chr20 50187983 50189983 CEBPB Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. human epithelial cells High+Lowthroughput PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation 否 nasopharyngeal carcinoma E_01_0359 Western blot, immunohistochemistry Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Immunohistochemical staining Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Western blot、免疫组化 CEBPB Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. 30910956 chr17 40306219 40308219 RARA Among them, rs10772119 and rs883868 disrupt the binding of retinoic acid receptor α (RARA) and Yin and Yang 1 (YY1), respectively. human High+Lowthroughput Risk variants disrupting enhancers of T(H)1 and T(REG) cells in type 2 diabetes 是 type 2 diabetes islet cell E_01_0360 ChIP-Seq Among them, rs10772119 and rs883868 disrupt the binding of retinoic acid receptor α (RARA) and Yin and Yang 1 (YY1), respectively. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Among them, rs10772119 and rs883868 disrupt the binding of retinoic acid receptor α (RARA) and Yin and Yang 1 (YY1), respectively. Immunohistochemical staining Among them, rs10772119 and rs883868 disrupt the binding of retinoic acid receptor α (RARA) and Yin and Yang 1 (YY1), respectively. ChIP-Seq RARA,YY1 Among them, rs10772119 and rs883868 disrupt the binding of retinoic acid receptor α (RARA) and Yin and Yang 1 (YY1), respectively.;Among them, rs10772119 and rs883868 disrupt the binding of retinoic acid receptor α (RARA) and Yin and Yang 1 (YY1), respectively. 30905509 chr3 133743290 133745290 TF This process is important to understand because induced pluripotency in somatic cells represents reversal of ontogeny and transcription factor (TF)- based reprogramming can leave vestiges of the original cell lineage. human Epithelial High+Lowthroughput Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA 否 enterocyte of epithelium of intestinal vi E_01_0361 ChIP-seq This process is important to understand because induced pluripotency in somatic cells represents reversal of ontogeny and transcription factor (TF)- based reprogramming can leave vestiges of the original cell lineage. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This process is important to understand because induced pluripotency in somatic cells represents reversal of ontogeny and transcription factor (TF)- based reprogramming can leave vestiges of the original cell lineage. Immunohistochemical staining This process is important to understand because induced pluripotency in somatic cells represents reversal of ontogeny and transcription factor (TF)- based reprogramming can leave vestiges of the original cell lineage. ChIP-seq TF This process is important to understand because induced pluripotency in somatic cells represents reversal of ontogeny and transcription factor (TF)- based reprogramming can leave vestiges of the original cell lineage. 30903020 chr7 148804044 148806044 EZH2 Robust expression of EZH2 in endocervical neoplastic lesions. human High+Lowthroughput Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma 否 fat cell E_01_0362 Chip SEQ, QRT PCR, Western blot test Robust expression of EZH2 in endocervical neoplastic lesions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Robust expression of EZH2 in endocervical neoplastic lesions. Immunohistochemical staining Robust expression of EZH2 in endocervical neoplastic lesions. ChIP-seq、qRT-PCR、免疫印迹测试 EZH2 Robust expression of EZH2 in endocervical neoplastic lesions. 30901906 chr2 28389918 28391918 FOSL2 We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. human connective High+Lowthroughput WNT3a and WNT5a Transported by Exosomes Activate WNT Signaling Pathways in Human Cardiac Fibroblasts 否 E_01_0363 Immunofluorescence staining, Western blot RT PCR We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. Immunohistochemical staining We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. 免疫荧光染色、Western blotRT-PCR FOSL2,MYC,RUNX1 We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS.;We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS.;We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. 30899425 chr12 55722375 55724375 CD63 Obtained exosomes showed size ranging between 20⁻150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. human High+Lowthroughput Super-enhancers: novel target for pancreatic ductal adenocarcinoma 否 pancreatic ductal adenocarcinoma E_01_0364 Chip SEQ, Western blot, PCR, immunohistochemistry, immunofluorescence staining Obtained exosomes showed size ranging between 20⁻150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Obtained exosomes showed size ranging between 20⁻150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. Immunohistochemical staining Obtained exosomes showed size ranging between 20⁻150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. ChIP-Seq、Western blot、PCR、免疫组化、免疫荧光染色 CD63 Obtained exosomes showed size ranging between 20⁻150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. 30898391 chr17 39401325 39403325 MED1 Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines. human Kidney High+Lowthroughput Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women 是 epithelial ovarian cancer E_01_0365 Bioinformatic prediction Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines. Immunohistochemical staining Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines. 生物信息学预测 NANOG,ESPNL MED1,SOX2 Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines.;At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene . Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines.;Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as SE in non-cancerous, cancerous and metastatic PDAC cell lines. 30894209 chr12 52484679 52486679 KRT6A This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. human High+Lowthroughput Hypoxia-induced miR-191-C/EBPβ signaling regulates cell proliferation and apoptosis of fibroblast-like synoviocytes from patients with rheumatoid arthritis 否 rheumatoid arthritis E_01_0366 RT-PCR, cell transfection techniques, Western blot This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Immunohistochemical staining This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. RT-PCR、细胞转染技术、Western blot KRT6A This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. 30892634 chr19 16322108 16324108 KLF2 KLF2 (kruppel-like factor 2 [lung]) regulates osteoclastogenesis by modulating autophagy. human High+Lowthroughput PLZF limits enhancer activity during hematopoietic progenitor aging 否 E_01_0367 RT qPCR, immunofluorescence staining, Western blot, ATAC seq KLF2 (kruppel-like factor 2 [lung]) regulates osteoclastogenesis by modulating autophagy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq KLF2 (kruppel-like factor 2 [lung]) regulates osteoclastogenesis by modulating autophagy. Immunohistochemical staining KLF2 (kruppel-like factor 2 [lung]) regulates osteoclastogenesis by modulating autophagy. RT-qPCR、免疫荧光染色、Western blot、ATAC-seq KLF2 KLF2 (kruppel-like factor 2 [lung]) regulates osteoclastogenesis by modulating autophagy. 30892142 chr3 108040340 108042340 CD47 CD47 enhancer-FIREFLY vec_x0002_tor was generated from the previously described construct CD47-E5. human High+Lowthroughput The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program 是 E_01_0368 ChIP-seq CD47 enhancer-FIREFLY vec_x0002_tor was generated from the previously described construct CD47-E5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CD47 enhancer-FIREFLY vec_x0002_tor was generated from the previously described construct CD47-E5. Immunohistochemical staining CD47 enhancer-FIREFLY vec_x0002_tor was generated from the previously described construct CD47-E5. ChIP-seq CD47 CD47 enhancer-FIREFLY vec_x0002_tor was generated from the previously described construct CD47-E5. 30888859 chr3 10139527 10141527 VHL Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. human High+Lowthroughput AMPK and PPARβ positive feedback loop regulates endurance exercise training-mediated GLUT4 expression in skeletal muscle 否 E_01_0369 Western blot, immunofluorescence staining Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Immunohistochemical staining Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Western blot、免疫荧光染色 VHL Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. 30886108 chr15 99562658 99564658 MEF2A We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. human High+Lowthroughput Gene activation precedes DNA demethylation in response to infection in human dendritic cells 否 E_01_0370 Gene knockdown We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Immunohistochemical staining We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. 基因敲降 KRT6A MEF2A KRT6A levels, metastasis‑associated factors and the Wnt/β‑catenin pathway were measured using RT‑qPCR and western blotting. We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. 30884312 chr15 99563063 99565063 MEF2A MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. human Cancer High+Lowthroughput PRISMA: Protein Interaction Screen on Peptide Matrix Reveals Interaction Footprints and Modifications- Dependent Interactome of Intrinsically Disordered C/EBPβ 否 preeclampsia E_01_0371 Bioinformatic predictions MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. Immunohistochemical staining MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. 生物药信息学预测 MEF2A MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. 30881868 chr16 56426207 56428207 NUDT21 The role of NUDT21 in microRNA-binging sites of EZH2 gene increases the of risk preeclampsia. human High+Lowthroughput ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells 否 E_01_0372 Immunohistochemistry, immunofluorescence staining, Western blot The role of NUDT21 in microRNA-binging sites of EZH2 gene increases the of risk preeclampsia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The role of NUDT21 in microRNA-binging sites of EZH2 gene increases the of risk preeclampsia. Immunohistochemical staining The role of NUDT21 in microRNA-binging sites of EZH2 gene increases the of risk preeclampsia. 免疫组化、免疫荧光染色、Western blot NUDT21 EZH2 The role of NUDT21 in microRNA-binging sites of EZH2 gene increases the of risk preeclampsia. The role of NUDT21 in microRNA-binging sites of EZH2 gene increases the of risk preeclampsia. 30881490 chr1 153658951 153660951 ILF2 ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells. human High+Lowthroughput The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β-catenin signaling 否 CRC E_01_0373 RT qPCR, Western blot / cell transfection ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells. Immunohistochemical staining ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells. RT-qPCR、Western blot/细胞转染技术 ILF2 ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells. 30879360 chr7 148804532 148806532 EZH2 EZH2 Inhibition in Ewing Sarcoma Upregulates G(D2) Expression for Targeting with Gene-Modified T Cells. human High+Lowthroughput Retinoic Acid Is a Negative Regulator of sFLT1 Expression in Decidual Stromal Cells, and Its Levels Are Reduced in Preeclamptic Decidua 否 E_01_0374 PCR, Western blot, immunofluorescence staining EZH2 Inhibition in Ewing Sarcoma Upregulates G(D2) Expression for Targeting with Gene-Modified T Cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 Inhibition in Ewing Sarcoma Upregulates G(D2) Expression for Targeting with Gene-Modified T Cells. Immunohistochemical staining EZH2 Inhibition in Ewing Sarcoma Upregulates G(D2) Expression for Targeting with Gene-Modified T Cells. PCR、Western blot、免疫荧光染色 EZH2 EZH2 Inhibition in Ewing Sarcoma Upregulates G(D2) Expression for Targeting with Gene-Modified T Cells. 33124415 chr9 70381888 70383888 KLF9 Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells. human High+Lowthroughput Mass Spectrometry-Based Metabolic Fingerprinting Contributes to Unveil the Role of RSUME in Renal Cell Carcinoma Cell Metabolism. 否 Clear cell renal cell carcinoma Renal cell E_01_0375 Cell transfection techniques, PCR Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells. Immunohistochemical staining Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells. 细胞转染技术、PCR KLF9 Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells. 32602275 chr3 10138986 10140986 VHL Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. human Epithelial High+Lowthroughput Enhancer-Gene Interaction Analyses Identified the Epidermal Growth Factor Receptor as a Susceptibility Gene for Type 2 Diabetes Mellitus. 是 type 2 diabetes islet cell E_01_0376 Bioinformatic prediction Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. Immunohistochemical staining Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. 生物信息学预测 VHL,EGFR Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene.;The SNP rs4947941 was annotated as an enhancer, and rs7785013 was located in the epidermal growth factor receptor (EGFR) gene. 31733305 chr4 152317572 152319572 FBXW7 FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. human Endothelial High+Lowthroughput The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors. 否 endothelial cell E_01_0377 PCR, gel electrophoresis, gene knockdown, immunofluorescence staining FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. Immunohistochemical staining FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. PCR、凝胶电泳、基因敲降、免疫荧光染色 SIX1 FBXW7,EZH2 FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling.;FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. 32408759 chr15 99562918 99564918 MEF2A MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. human Embryonic High+Lowthroughput Variants in miRNA regulome and their association with the risk of nonsyndromi corofacial clefts 否 nonsyndromic orofacial clefts embryonic cell E_01_0378 PCR MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. Immunohistochemical staining MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. PCR MEF2A MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells. 33009960 chr17 76373734 76375734 SPHK1 Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. human Immunohistochem High+Lowthroughput Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2 否 leukocyte E_01_0379 gel electrophoresis Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. Immunohistochemical staining Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. 凝胶电泳 SPHK1 Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. 32094355 chr1 153658363 153660363 ILF2 Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. human Epithelial High+Lowthroughput Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas 否 uterine leiomyomas uterine smooth muscle cell E_01_0380 PCR Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. Immunohistochemical staining Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. PCR ILF2 Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. 32736380 chrX 71115647 71117647 MED12 Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas. human High+Lowthroughput Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories 否 stem cell E_01_0381 PCR Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas. Immunohistochemical staining Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas. PCR MED12 Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas. 33203992 chr3 128476653 128478653 GATA2 Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories. human Thyroid High+Lowthroughput Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma 是 papillary thyroid carcinoma thyroid gland cell E_01_0382 PCR Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories. Immunohistochemical staining Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories. PCR EPB41L4A GATA2 Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma. Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories. 31411680 chr7 148804636 148806636 EZH2 A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy . human Brain High+Lowthroughput [Noncoding Polymorphism rs6832152 Is an Attractive Candidate for Genome Editing Aimed at Finding New Molecular Mechanisms of Autoimmune Diseases]. 否 brain cell E_01_0383 Single cell sequencing A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy . Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy . Immunohistochemical staining A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy . 单细胞测序 EZH2 A systems approach identifies Enhancer of Zeste Homolog 2 (EZH2) as a protective factor in epilepsy . 30896882 chr1 95231641 95233641 RWDD3 Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. human High+Lowthroughput 否 nasopharyngeal carcinoma E_01_0384 RT qPCR, Western blot, cell transfection Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. Immunohistochemical staining Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. RT-qPCR、Western blot、细胞转染技术 RWDD3 Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. 34531368 chrX 67540972 67542972 AR The androgen receptor (AR) is commonly known as a key transcription factor in prostate cancer development, progression and therapy resistance. human Immune cells High+Lowthroughput Androgen receptor enhancer usage and the chromatin regulatory landscape in human prostate cancers. 否 genomically silent childhood cancer EwS cell E_01_0385 PCR The androgen receptor (AR) is commonly known as a key transcription factor in prostate cancer development, progression and therapy resistance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The androgen receptor (AR) is commonly known as a key transcription factor in prostate cancer development, progression and therapy resistance. Immunohistochemical staining The androgen receptor (AR) is commonly known as a key transcription factor in prostate cancer development, progression and therapy resistance. PCR AR The androgen receptor (AR) is commonly known as a key transcription factor in prostate cancer development, progression and therapy resistance. 34294917 chr16 23675330 23677330 PLK1 Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer . human High+Lowthroughput Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer. 否 brain cell E_01_0386 RNA SEQ, gel electrophoresis Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer . Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer . Immunohistochemical staining Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer . RNA-seq、凝胶电泳 PLK1 Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer . 33704060 chr6 1607232 1609232 FOXC1 Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. human Epithelial High+Lowthroughput Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes. 否 epithelial cell E_01_0387 Gel electrophoresis, PCR Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Immunohistochemical staining Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. 凝胶电泳、PCR WT1,LMX1B FOXC1,FOXC2 Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B.;Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B.;Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. 29941091 chr16 67559331 67561331 CTCF The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones. human lymphoid High+Lowthroughput The human leukemia virus HTLV-1 alters the structure and transcription of host chromatin in cis 是 leukemia T lymphocyte E_01_0388 q4C,CRISPR/Cas9,RNA-seq,ChIP-seq,WGS, The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones. Immunohistochemical staining The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones. q4C,CRISPR/Cas9,RNA-seq,ChIP-seq,WGS, PRC1 CTCF,YY1 The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones. The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones.;The altered chromosomal looping and consequent effects on host genome transcription depend on the proviral integration site and the presence of nearby CTCF-BS, and so differ in each infected T-cell clone. The changes in chromatin structure caused by HTLV-1 might not only create novel loops but also destroy pre-existing CTCF-dependent loops that are present in uninfected cells. Further work is needed to investigate the impact of altered looping and transcription on the persistence, infectivity and oncogenic potential of the infected T-cell clones. 29940916 chr7 148804605 148806605 EZH2 We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, aglobal repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. human Mammary High+Lowthroughput Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma 否 mammary cancer epithelial cell E_01_0389 Immunohistochemistry,transfection,Western blot,CHIP,qRT-PCR,CHIP-qPCR, We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, aglobal repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, aglobal repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. Immunohistochemical staining We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, aglobal repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. Immunohistochemistry,transfection,Western blot,CHIP,qRT-PCR,CHIP-qPCR, EZH2 We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, aglobal repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo. 29940792 chr16 87381402 87383402 MAP1LC3B These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction. human Liver High+Lowthroughput Peritumoral monocytes induce cancer cell autophagy to facilitate the progression of human hepatocellular carcinoma 否 Hepatocellular carcinoma monocyte cells E_01_0390 Immunofluorescence,Immunohistochemical Staining,qRT-PCR,Immunoblotting,Transmission electron microscopy,ELISA,RNA interference, These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction. Immunohistochemical staining These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction. Immunofluorescence,Immunohistochemical Staining,qRT-PCR,Immunoblotting,Transmission electron microscopy,ELISA,RNA interference, MAP1LC3B TNF,IL1B,SNAI1 These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction. These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction.;These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction.;These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction. 29934339 chr16 53698968 53700968 FTO We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd/CEBPD expression in murine and human adipocytes in vitro. Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming is conveyed, in part, by modulation of C/ebpβ-regulated transcription. We find that Fto also affects Cebpd transcription by demethylating DNA N6-methyldeoxyadenosine in the Cebpd promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of Cebpd. These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative Fto allele. human adipose High+Lowthroughput FTO mediates cell-autonomous effects on adipogenesis and adipocyte lipid content by regulating gene expression via 6mA DNA modifications 是 rs9939609,rs8050136,rs1421085 Diabetes mellitus, obesity fat cell E_01_0391 transfection,RNA expression studies, RNA-Seq,m6A-RIP,6mA DNA Immunoprecipitation,Lipid Staining,Quantitative real time PCR,ChIP,Western blot, We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd/CEBPD expression in murine and human adipocytes in vitro. Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming is conveyed, in part, by modulation of C/ebpβ-regulated transcription. We find that Fto also affects Cebpd transcription by demethylating DNA N6-methyldeoxyadenosine in the Cebpd promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of Cebpd. These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative Fto allele. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd/CEBPD expression in murine and human adipocytes in vitro. Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming is conveyed, in part, by modulation of C/ebpβ-regulated transcription. We find that Fto also affects Cebpd transcription by demethylating DNA N6-methyldeoxyadenosine in the Cebpd promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of Cebpd. These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative Fto allele. Immunohistochemical staining We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd/CEBPD expression in murine and human adipocytes in vitro. Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming is conveyed, in part, by modulation of C/ebpβ-regulated transcription. We find that Fto also affects Cebpd transcription by demethylating DNA N6-methyldeoxyadenosine in the Cebpd promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of Cebpd. These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative Fto allele. transfection,RNA expression studies, RNA-Seq,m6A-RIP,6mA DNA Immunoprecipitation,Lipid Staining,Quantitative real time PCR,ChIP,Western blot, FTO CEBPB We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd/CEBPD expression in murine and human adipocytes in vitro. Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming is conveyed, in part, by modulation of C/ebpβ-regulated transcription. We find that Fto also affects Cebpd transcription by demethylating DNA N6-methyldeoxyadenosine in the Cebpd promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of Cebpd. These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative Fto allele. We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd/CEBPD expression in murine and human adipocytes in vitro. Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming is conveyed, in part, by modulation of C/ebpβ-regulated transcription. We find that Fto also affects Cebpd transcription by demethylating DNA N6-methyldeoxyadenosine in the Cebpd promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of Cebpd. These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative Fto allele. 29932212 chr21 34784999 34786999 RUNX1 CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy. human Nervous High+Lowthroughput CSF3R Mutations are frequently associated with abnormalities of RUNX1, CBFB, CEBPA, and NPM1 genes in acute myeloid leukemia 否 Acute myeloid leukemia neutrophils E_01_0392 DNA-Seq,RT-PCR,Mutation Analysis, CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy. Immunohistochemical staining CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy. DNA-Seq,RT-PCR,Mutation Analysis, NPM1,CSF3R RUNX1,CBFB,CEBPA CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy.;CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy. CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy.;CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy.;CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core-binding factor gene abnormalities and CEBPAdm. An in-depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy. 29929436 chr1 45508017 45510017 PRDX1 Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity. human Epithelial High+Lowthroughput Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation 否 Other THP-1 E_01_0393 Luciferase reporter assay,Western blot,Immunoprecipitation (IP),qRT-PCR,Immunofluorescence microscopy,Salmonella Infection Assay,transwell migration assay, Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity. Immunohistochemical staining Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity. Luciferase reporter assay,Western blot,Immunoprecipitation (IP),qRT-PCR,Immunofluorescence microscopy,Salmonella Infection Assay,transwell migration assay, PRDX1,TRAF6,BECN1 TLR4 Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity.;Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity.;Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity. Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity. 29928592 chr8 19898949 19900949 LPL TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances. human Nervous High+Lowthroughput Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD 否 mesenchymal stem cell E_01_0394 RT-qPCR,oil red O staining,ALP activity assay,cell matrix ALP staining, alizarin red S staining, TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances. Immunohistochemical staining TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances. RT-qPCR,oil red O staining,ALP activity assay,cell matrix ALP staining, alizarin red S staining, LPL TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances. 29928447 chr2 15937740 15939740 MYCN The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine. human High+Lowthroughput Cancer panel analysis of circulating tumor cells in patients with breast cancer 否 mammary cancer NCI-H358 E_01_0395 Immunofluorescent staining,Whole genome amplification,CCP, The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine. Immunohistochemical staining The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine. Immunofluorescent staining,Whole genome amplification,CCP, MYCN,APC The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine.;The CTC-specific mutations were enhancer of zeste polycomb repressive complex 2 subunit, notch 1, AT-rich interaction domain 1A, serine/threonine kinase 11, fms related tyrosine kinase 3, MYCN proto-oncogene, bHLH transcription factor, APC, WNT signaling pathway regulator, and phosphatase and tensin homolog. The technique used by the present study was demonstrated to be effective at isolating CTCs at a sufficiently high purity for genomic analysis, and supported the use of comprehensive cancer panel analysis as a potential application for precision medicine. 29928394 chr10 52311539 52313539 DKK1 In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy. human Lung cancer High+Lowthroughput Prediction and identification of transcriptional regulatory elements at the lung cancer-specific DKK1 locus 否 lung cancer E_01_0396 PCR,Plasmid transfection,Firefly/Renilla luciferase quantification, In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy. Immunohistochemical staining In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy. PCR,Plasmid transfection,Firefly/Renilla luciferase quantification, DKK1 In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy. 29927026 chr4 108044908 108046908 LEF1 Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis human Skeletal High+Lowthroughput Novel lymphoid enhancer-binding factor 1-cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs 否 Osteosarcoma (OS) LM8-C3H E_01_0397 Histology analysis,Western blot,Cell‐proliferation assay,Extravasation assay,Cell‐adhesion assay,Transmigration assay,Genomewide meta‐analysis,Reverse transcription‐PCR,qPCR,CRISPR‐Cas9 , Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis Immunohistochemical staining Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis Histology analysis,Western blot,Cell‐proliferation assay,Extravasation assay,Cell‐adhesion assay,Transmigration assay,Genomewide meta‐analysis,Reverse transcription‐PCR,qPCR,CRISPR‐Cas9 , Cygb,CYGB LEF1 Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis;Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis Our results showed a novel LEF1‐CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis 29925637 chr3 185640391 185642391 IGF2BP2 We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis. human adipose High+Lowthroughput Interrogation of nonconserved human adipose lincRNAs identifies a regulatory role of linc-ADAL in adipocyte metabolism 否 Other fat cell E_01_0398 RNA knockdown,RNA-seq,ChIP-seq,Western blot, immunoblot, CLIP-seq, We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis. Immunohistochemical staining We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis. RNA knockdown,RNA-seq,ChIP-seq,Western blot, immunoblot, CLIP-seq, IGF2BP2 We demonstrated that linc-ADAL interacts with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) at distinct subcellular locations to regulate adipocyte differentiation and lipogenesis. 29923177 chr10 22317950 22319950 BMI1 At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. human lymphoid High+Lowthroughput BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia 是 rs11591377,rs4748812 Childhood acute lymphoblastic leukaemia (all) E_01_0399 CHIP-seq,GWS,Enhancer assay,H3k27ac HiChIP data analysis,MethylC-Seq Analysis,Transcription factor binding analysis, At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. Immunohistochemical staining At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. CHIP-seq,GWS,Enhancer assay,H3k27ac HiChIP data analysis,MethylC-Seq Analysis,Transcription factor binding analysis, PIP4K2A BMI1,MYBL2,RUNX1,ARID5B,IKZF1,CEBPE,GATA3 At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.;At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.;At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.;At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.;At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.;At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A.;At PIP4K2A, we identified rs4748812 (Pmeta=1.3x10-15), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. 29916899 chr11 65495083 65497083 MALAT1 MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC. human Esophageal High+Lowthroughput LncRNA MALAT1 promotes epithelial-to-mesenchymal transition of esophageal cancer through Ezh2-Notch1 signaling pathway 否 Esophageal cancer (EC) TE-1 E_01_0400 transfection,RT-PCR,Western blot, MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC. Immunohistochemical staining MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC. transfection,RT-PCR,Western blot, Ezh2,Notch1,Hes1 MALAT1 MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC.;MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC.;MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC. MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC. 29915186 chr4 108045032 108047032 LEF1 Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway. human Nervous High+Lowthroughput BMP and WNT signalling cooperate through LEF1 in the neuronal specification of adult hippocampal neural stem and progenitor cells 否 Hippocampal dentate gyrus E_01_0401 Immunostaining,Gene Expression analysis,Western blot,ChIP, Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway. Immunohistochemical staining Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway. Immunostaining,Gene Expression analysis,Western blot,ChIP, LEF1 Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway. 29914089 chr5 17983939 17985939 Cd36 Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways. mouse Epithelial High+Lowthroughput Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis 否 cancer MCF-7 E_01_0402 Reverse Transcription-PCR,Western Blot,EMSA,Wound Healing Assay,Matrigel Invasion Assay,siRNA Analysis,In vitro Angiogenesis Assay,Molecular Docking, Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways. Immunohistochemical staining Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways. Reverse Transcription-PCR,Western Blot,EMSA,Wound Healing Assay,Matrigel Invasion Assay,siRNA Analysis,In vitro Angiogenesis Assay,Molecular Docking, Cd36,Stat3 Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.;Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways. 29913133 chr1 209782740 209784740 IRF6 Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide. human Epithelial High+Lowthroughput IRF6 and AP2A Interaction Regulates Epidermal Development 否 rs642961 Van der Woude syndrome (cleft lip / palate), popliteal pterygium syndrome (eye disease) epidermal cell E_01_0403 Western blot, Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide. Immunohistochemical staining Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide. Western blot, Tfap2c,Tfap2a,Irf6 IRF6,TP63,GRHL3 Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide.;Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide.;Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide. Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide.;Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide.;Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide. 29911120 chr13 40552875 40554875 FOXO1 Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia. human Nervous High+Lowthroughput Apoptosis induction in acute promyelocytic leukemia cells through upregulation of CEBPα by miR-182 blockage 否 Acute promyelocytic leukemia HL-60 E_01_0404 Cell transfection,Reverse transcriptase microRNA real-time PCR,qRT-PCR,Cell viability assay, Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia. Immunohistochemical staining Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia. Cell transfection,Reverse transcriptase microRNA real-time PCR,qRT-PCR,Cell viability assay, FOXO1 Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia. 29909987 chrX 67541571 67543571 AR Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. human connective High+Lowthroughput A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer 否 prostatic cancer E_01_0405 PCR,CRISPR/Cas9,Proliferation Assays,Competition Experiments,Quantitative RT-PCR,Immunoblotting,Cloning,Chromosome Conformation Capture(3C),Crystal Violet Proliferation Assays,ChIP-seq,ChIP,ChIP-qPCR,Whole-Genome Bisulfite Sequencing analysis(WGBS), Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. Immunohistochemical staining Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. PCR,CRISPR/Cas9,Proliferation Assays,Competition Experiments,Quantitative RT-PCR,Immunoblotting,Cloning,Chromosome Conformation Capture(3C),Crystal Violet Proliferation Assays,ChIP-seq,ChIP,ChIP-qPCR,Whole-Genome Bisulfite Sequencing analysis(WGBS), EIF4A3,SF3B3,RPL23 AR Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers.;Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers.;Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers. 29909985 chrX 67541233 67543233 AR A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. human Myotome High+Lowthroughput Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing 否 Metastatic castration resistant prostate cancer (mcrpc) LNCaP E_01_0406 WGS,qPCR,Hi-C,CHIP,DNA seq, A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. Immunohistochemical staining A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. WGS,qPCR,Hi-C,CHIP,DNA seq, CDK12 AR,MYC A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered.;A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. 29909962 chr8 11792732 11794732 FDFT1 Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady state. human connective High+Lowthroughput Squalene Synthase Deficiency: Clinical, Biochemical, and Molecular Characterization of a Defect in Cholesterol Biosynthesis 否 Squalene synthase deficiency fibroblast E_01_0407 PCR,WES,Western blot, Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady state. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady state. Immunohistochemical staining Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady state. PCR,WES,Western blot, FDFT1 Whole-exome sequencing was used to identify recessive disease-causing variants in FDFT1. Functional characterization of one variant demonstrated a partial splicing defect and altered promoter and/or enhancer activity, reflecting essential mechanisms for regulating cholesterol biosynthesis/uptake in steady state. 29908199 chrX 55006337 55008337 ALAS2 These results suggest that the induction of mitochondrial ferritin expression might be essential for, but not the primary cause of, ring sideroblast formation. Our results also suggest that the insufficient supply of protoporphyrin IX due to ALAS2 deficiency in combination with increased iron import into mitochondria during erythroid differentiation results in the formation of ring sideroblasts. Furthermore, HA2low cells are a useful tool for characterizing ring sideroblasts in vitro. human connective High+Lowthroughput Establishment of a cell model of X-linked sideroblastic anemia using genome editing 否 X-linked sideroblastic anemia E_01_0408 Quantitative real-time polymerase chain reaction,Western blot,Electron microscopy,Flow cytometry,Staining, These results suggest that the induction of mitochondrial ferritin expression might be essential for, but not the primary cause of, ring sideroblast formation. Our results also suggest that the insufficient supply of protoporphyrin IX due to ALAS2 deficiency in combination with increased iron import into mitochondria during erythroid differentiation results in the formation of ring sideroblasts. Furthermore, HA2low cells are a useful tool for characterizing ring sideroblasts in vitro. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that the induction of mitochondrial ferritin expression might be essential for, but not the primary cause of, ring sideroblast formation. Our results also suggest that the insufficient supply of protoporphyrin IX due to ALAS2 deficiency in combination with increased iron import into mitochondria during erythroid differentiation results in the formation of ring sideroblasts. Furthermore, HA2low cells are a useful tool for characterizing ring sideroblasts in vitro. Immunohistochemical staining These results suggest that the induction of mitochondrial ferritin expression might be essential for, but not the primary cause of, ring sideroblast formation. Our results also suggest that the insufficient supply of protoporphyrin IX due to ALAS2 deficiency in combination with increased iron import into mitochondria during erythroid differentiation results in the formation of ring sideroblasts. Furthermore, HA2low cells are a useful tool for characterizing ring sideroblasts in vitro. Quantitative real-time polymerase chain reaction,Western blot,Electron microscopy,Flow cytometry,Staining, ALAS2 These results suggest that the induction of mitochondrial ferritin expression might be essential for, but not the primary cause of, ring sideroblast formation. Our results also suggest that the insufficient supply of protoporphyrin IX due to ALAS2 deficiency in combination with increased iron import into mitochondria during erythroid differentiation results in the formation of ring sideroblasts. Furthermore, HA2low cells are a useful tool for characterizing ring sideroblasts in vitro. 29907596 chr17 44074243 44076243 HDAC5 In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies. human Nervous High+Lowthroughput Inflammation leads through PGE/EP(3) signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes 否 Inflammatory cardiomyopathy nrvm E_01_0409 Luciferase reporter assay,Immunoblotting,Immunostaining,RNA analysis,Western Blot In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies. Immunohistochemical staining In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies. Luciferase reporter assay,Immunoblotting,Immunostaining,RNA analysis,Western Blot HDAC5 In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies. 29906314 chr6 38673142 38675142 GLO1 We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element activation. Inflammatory targets, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and tumor necrosis factor alpha, were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. human connective High+Lowthroughput Gromwell (Lithospermum erythrorhizon) root extract protects against glycation and related inflammatory and oxidative stress while offering UV absorption capability 否 Glycosylation HepG2 cell E_01_0410 qRT-PCR,qPCR We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element activation. Inflammatory targets, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and tumor necrosis factor alpha, were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element activation. Inflammatory targets, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and tumor necrosis factor alpha, were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. Immunohistochemical staining We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element activation. Inflammatory targets, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and tumor necrosis factor alpha, were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. qRT-PCR,qPCR GLO1 We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element activation. Inflammatory targets, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and tumor necrosis factor alpha, were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. 29905573 chr7 148804380 148806380 EZH2 Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti-CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab. human lymphoid High+Lowthroughput Modulation of EZH2 expression in T cells improves efficacy of anti-CTLA-4 therapy 否 tumour T cell E_01_0411 RNA-seq Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti-CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti-CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab. Immunohistochemical staining Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti-CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab. RNA-seq EZH2 Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti-CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab. 29899688 chr21 25877858 25879858 APP To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-α by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-κB signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-α. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-κB-dependent mechanism. As the major components of γ-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of Aβ, which in turn activates TNF-α in glial cells. Reciprocally, TNF-α stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-α and Aβ in glial cells and neurons could ultimately aggravate the development and progression of AD. human Nervous High+Lowthroughput Magnesium Ions Inhibit the Expression of Tumor Necrosis Factor α and the Activity of γ-Secretase in a β-Amyloid Protein-Dependent Mechanism in APP/PS1 Transgenic Mice 否 Alzheimer's disease (AD) A172 E_01_0412 transgenic mice,qRT-PCR,SDS-PAGE,Western blot,Immunohistochemistry, To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-α by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-κB signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-α. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-κB-dependent mechanism. As the major components of γ-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of Aβ, which in turn activates TNF-α in glial cells. Reciprocally, TNF-α stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-α and Aβ in glial cells and neurons could ultimately aggravate the development and progression of AD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-α by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-κB signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-α. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-κB-dependent mechanism. As the major components of γ-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of Aβ, which in turn activates TNF-α in glial cells. Reciprocally, TNF-α stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-α and Aβ in glial cells and neurons could ultimately aggravate the development and progression of AD. Immunohistochemical staining To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-α by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-κB signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-α. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-κB-dependent mechanism. As the major components of γ-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of Aβ, which in turn activates TNF-α in glial cells. Reciprocally, TNF-α stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-α and Aβ in glial cells and neurons could ultimately aggravate the development and progression of AD. transgenic mice,qRT-PCR,SDS-PAGE,Western blot,Immunohistochemistry, APP To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively. Our data demonstrates that magnesium-L-threonate (MgT) can decrease the expression of TNF-α by restoring the levels of Mg2+ in glial cells. In addition, PI3-K/AKT and NF-κB signals play critical roles in mediating the effects of Mg2+ on suppressing the expression of TNF-α. In neurons, Mg2+ elevation showed similar suppressive effects on the expression of presenilin enhancer 2 (PEN2) and nicastrin (NCT) through a PI3-K/AKT and NF-κB-dependent mechanism. As the major components of γ-secretase, overexpression of presenilin 1 (PS1), PEN2 and NCT potentially promote the synthesis of Aβ, which in turn activates TNF-α in glial cells. Reciprocally, TNF-α stimulates the expression of PEN2 and NCT in neurons. The crosstalk between TNF-α and Aβ in glial cells and neurons could ultimately aggravate the development and progression of AD. 29898397 chr7 148805021 148807021 EZH2 Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. human lymphoid High+Lowthroughput Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity 否 cancer lymphocyte E_01_0413 Flow Cytometry,Histology, RNA-seq,transgenic mice Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. Immunohistochemical staining Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. Flow Cytometry,Histology, RNA-seq,transgenic mice EZH2,FOXP3 Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity.;Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. 29896299 chr2 216669551 216671551 IGFBP5 Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis. human Epithelial High+Lowthroughput Flow-dependent epigenetic regulation of IGFBP5 expression by H3K27me3 contributes to endothelial anti-inflammatory effects 否 atherosclerosis HUVECs E_01_0414 ChIP,RNA-seq,ChIP-qPCR,Western blot ,siRNA,miRNA transfection,Luciferase reporter assay,immunofluorescent staining, Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis. Immunohistochemical staining Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis. ChIP,RNA-seq,ChIP-qPCR,Western blot ,siRNA,miRNA transfection,Luciferase reporter assay,immunofluorescent staining, IGFBP5 EZH2 Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis. Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium. Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis. 29894816 chr2 136111792 136113792 CXCR4 The current results indicate that 4DV3 might serve as a prototype for a new type of dual function ligand, one that acts as a HIV-1 entry inhibitor and a CXCR4 drug delivery targeting ligand. human lymphoid High+Lowthroughput Design and evaluation of a CXCR4 targeting peptide 4DV3 as an HIV entry inhibitor and a ligand for targeted drug delivery 否 AIDS E_01_0415 competitive binding assay,MTT assay,luciferase activity The current results indicate that 4DV3 might serve as a prototype for a new type of dual function ligand, one that acts as a HIV-1 entry inhibitor and a CXCR4 drug delivery targeting ligand. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The current results indicate that 4DV3 might serve as a prototype for a new type of dual function ligand, one that acts as a HIV-1 entry inhibitor and a CXCR4 drug delivery targeting ligand. Immunohistochemical staining The current results indicate that 4DV3 might serve as a prototype for a new type of dual function ligand, one that acts as a HIV-1 entry inhibitor and a CXCR4 drug delivery targeting ligand. competitive binding assay,MTT assay,luciferase activity CXCR4 The current results indicate that 4DV3 might serve as a prototype for a new type of dual function ligand, one that acts as a HIV-1 entry inhibitor and a CXCR4 drug delivery targeting ligand. 29889836 chr1 169719974 169721974 SELE In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES. human Epithelial High+Lowthroughput Endothelial cell activation is attenuated by everolimus via transcriptional and post-transcriptional regulatory mechanisms after drug-eluting coronary stenting 否 Other HCAEC E_01_0416 RT-qPCR,ELISA,ChIP-seq,Transfection, In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES. Immunohistochemical staining In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES. RT-qPCR,ELISA,ChIP-seq,Transfection, SELE,VCAM1 In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES.;In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES. 29888110 chr4 7751285 7753285 AFAP1-AS1 Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment. human Colon High+Lowthroughput Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer 否 colorectal cancer LOVO cell E_01_0417 ChIP-qPCR,RNA pull-down assay,RNA immunoprecipitation,RNA extraction,quantitative RT-PCR,Western blot, Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment. Immunohistochemical staining Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment. ChIP-qPCR,RNA pull-down assay,RNA immunoprecipitation,RNA extraction,quantitative RT-PCR,Western blot, AFAP1-AS1 EZH2 Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment. Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment. 29887316 chr22 39516355 39518355 ATF4 ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD. human Liver High+Lowthroughput Palmitate deranges erythropoietin production via transcription factor ATF4 activation of unfolded protein response 否 Chronic kidney injury HepG2 E_01_0418 Oil red O staining,Western blot,Luciferase assays,quantitative real-time PCR,Histological analysis,Immunofluorescence analysis,Electron microscopy,Laser microdissection, ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD. Immunohistochemical staining ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD. Oil red O staining,Western blot,Luciferase assays,quantitative real-time PCR,Histological analysis,Immunofluorescence analysis,Electron microscopy,Laser microdissection, ATF4,EPO ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD.;ATF4 knockdown by siRNA significantly attenuated the suppressive effect of palmitate on EPO production. Studies utilizing inherited super-anemic mice (ISAM) mated with EPO-Cre mice (ISAM-REC mice) for lineage-labeling of REP cells showed that ATF4 activation by palmitate suppressed EPO production in REP cells. Laser capture microdissection confirmed ATF4 activation in the interstitial area of ISAM-REC mice treated with palmitate-conjugated BSA. Thus, endoplasmic reticulum stress induced by palmitate suppressed EPO expression by REP cells in a manner independent of HIF activation. The link between endoplasmic reticulum stress, dyslipidemia, and hypoxia may contribute to development and progression of anemia in CKD. 29885843 chr11 46853631 46855631 LRP4 Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target. human Parathyroid High+Lowthroughput LRP4 promotes proliferation, migration, and invasion in papillary thyroid cancer 否 Thyroid cancer TPC1 E_01_0419 qRT-PCR,Cell transfection,Cell proliferation assay,Colony formation assay,Cell migration and invasion assays,Western blot,LRP4 siRNA Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target. Immunohistochemical staining Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target. qRT-PCR,Cell transfection,Cell proliferation assay,Colony formation assay,Cell migration and invasion assays,Western blot,LRP4 siRNA LRP4 EZH2,ZEB1 Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target. Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target.;Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target. 29885461 chr6 131945329 131947329 CCN2 Loss of CCN2 in CAFs resulted in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, and reduced tumor-induced neovascularization, as detected by micro-computed tomography (micro-CT) and staining with anti-CD31 antibodies. CCN2-deficient B16(F10) cells were defective in a tubule formation/vasculogenic mimicry assay in vitro. Mice deleted for CCN2 in CAFs also showed impaired vasculogenic mimicry of subcutaneously-injected B16-F10 cells in vivo. Our results provide new insights into the cross-talk among different cell types in the tumor microenvironment and suggest CAFs play a heretofore unappreciated role by being essential for tumor neovascularization via the production of CCN2. Our data are consistent with the hypothesis that activated CAFs are essential for melanoma metastasis and that, due to its role in this process, CCN2 is a therapeutic target for melanoma. human Nervous High+Lowthroughput Activation of cancer-associated fibroblasts is required for tumor neovascularization in a murine model of melanoma 否 Metastatic melanoma B16-F10 E_01_0420 ELISA,Histological analysis,transfection,RNA-seq,immunohistochemistry experiments, Loss of CCN2 in CAFs resulted in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, and reduced tumor-induced neovascularization, as detected by micro-computed tomography (micro-CT) and staining with anti-CD31 antibodies. CCN2-deficient B16(F10) cells were defective in a tubule formation/vasculogenic mimicry assay in vitro. Mice deleted for CCN2 in CAFs also showed impaired vasculogenic mimicry of subcutaneously-injected B16-F10 cells in vivo. Our results provide new insights into the cross-talk among different cell types in the tumor microenvironment and suggest CAFs play a heretofore unappreciated role by being essential for tumor neovascularization via the production of CCN2. Our data are consistent with the hypothesis that activated CAFs are essential for melanoma metastasis and that, due to its role in this process, CCN2 is a therapeutic target for melanoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Loss of CCN2 in CAFs resulted in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, and reduced tumor-induced neovascularization, as detected by micro-computed tomography (micro-CT) and staining with anti-CD31 antibodies. CCN2-deficient B16(F10) cells were defective in a tubule formation/vasculogenic mimicry assay in vitro. Mice deleted for CCN2 in CAFs also showed impaired vasculogenic mimicry of subcutaneously-injected B16-F10 cells in vivo. Our results provide new insights into the cross-talk among different cell types in the tumor microenvironment and suggest CAFs play a heretofore unappreciated role by being essential for tumor neovascularization via the production of CCN2. Our data are consistent with the hypothesis that activated CAFs are essential for melanoma metastasis and that, due to its role in this process, CCN2 is a therapeutic target for melanoma. Immunohistochemical staining Loss of CCN2 in CAFs resulted in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, and reduced tumor-induced neovascularization, as detected by micro-computed tomography (micro-CT) and staining with anti-CD31 antibodies. CCN2-deficient B16(F10) cells were defective in a tubule formation/vasculogenic mimicry assay in vitro. Mice deleted for CCN2 in CAFs also showed impaired vasculogenic mimicry of subcutaneously-injected B16-F10 cells in vivo. Our results provide new insights into the cross-talk among different cell types in the tumor microenvironment and suggest CAFs play a heretofore unappreciated role by being essential for tumor neovascularization via the production of CCN2. Our data are consistent with the hypothesis that activated CAFs are essential for melanoma metastasis and that, due to its role in this process, CCN2 is a therapeutic target for melanoma. ELISA,Histological analysis,transfection,RNA-seq,immunohistochemistry experiments, CCN2,COL1A2 Loss of CCN2 in CAFs resulted in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, and reduced tumor-induced neovascularization, as detected by micro-computed tomography (micro-CT) and staining with anti-CD31 antibodies. CCN2-deficient B16(F10) cells were defective in a tubule formation/vasculogenic mimicry assay in vitro. Mice deleted for CCN2 in CAFs also showed impaired vasculogenic mimicry of subcutaneously-injected B16-F10 cells in vivo. Our results provide new insights into the cross-talk among different cell types in the tumor microenvironment and suggest CAFs play a heretofore unappreciated role by being essential for tumor neovascularization via the production of CCN2. Our data are consistent with the hypothesis that activated CAFs are essential for melanoma metastasis and that, due to its role in this process, CCN2 is a therapeutic target for melanoma.;Loss of CCN2 in CAFs resulted in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, and reduced tumor-induced neovascularization, as detected by micro-computed tomography (micro-CT) and staining with anti-CD31 antibodies. CCN2-deficient B16(F10) cells were defective in a tubule formation/vasculogenic mimicry assay in vitro. Mice deleted for CCN2 in CAFs also showed impaired vasculogenic mimicry of subcutaneously-injected B16-F10 cells in vivo. Our results provide new insights into the cross-talk among different cell types in the tumor microenvironment and suggest CAFs play a heretofore unappreciated role by being essential for tumor neovascularization via the production of CCN2. Our data are consistent with the hypothesis that activated CAFs are essential for melanoma metastasis and that, due to its role in this process, CCN2 is a therapeutic target for melanoma. 29885262 chr1 55036580 55038580 PCSK9 We, therefore, studied the effect of PCSK9 on interferon (IFN) β expression. We show that PCSK9 decreases IFNβ promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFNβ promoter/enhancer activity. Moreover, PCSK9 decreases IFNβ promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNβ enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. human Liver High+Lowthroughput Proprotein convertase subtilisin/kexin type 9 inhibits interferon β expression through interacting with ATF-2 否 cancer Huh-7 cell E_01_0421 transcription,luciferase assay,Western blot,RT-qPCR,ELISA,ChIP, We, therefore, studied the effect of PCSK9 on interferon (IFN) β expression. We show that PCSK9 decreases IFNβ promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFNβ promoter/enhancer activity. Moreover, PCSK9 decreases IFNβ promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNβ enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We, therefore, studied the effect of PCSK9 on interferon (IFN) β expression. We show that PCSK9 decreases IFNβ promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFNβ promoter/enhancer activity. Moreover, PCSK9 decreases IFNβ promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNβ enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. Immunohistochemical staining We, therefore, studied the effect of PCSK9 on interferon (IFN) β expression. We show that PCSK9 decreases IFNβ promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFNβ promoter/enhancer activity. Moreover, PCSK9 decreases IFNβ promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNβ enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. transcription,luciferase assay,Western blot,RT-qPCR,ELISA,ChIP, PCSK9 We, therefore, studied the effect of PCSK9 on interferon (IFN) β expression. We show that PCSK9 decreases IFNβ promoter/enhancer activity, mRNA and protein levels, and its downstream 2',5'-oligoadenylate synthetase-1 mRNA level. ProPCSK9, but not the cleaved PCSK9, down-regulates IFNβ promoter/enhancer activity. Moreover, PCSK9 decreases IFNβ promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor-2 (ATF-2)/c-Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK9 and ATF-2, which reduces ATF-2/c-Jun dimerization and ATF-2/c-Jun binding to the IFNβ enhancer. This novel function of PCSK9 should have important implications in optimizing the clinical use of PCSK9 inhibitors. 29884649 chr13 110709998 110711998 ING1 Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers and, cooperatively with ING1, promotes local DNA demethylation via long-range chromatin loops to permit C/EBPβ recruitment. The results indicate that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process. Our study suggests a causal nexus between DNA demethylation, metabolism, and organismal aging. human Nervous High+Lowthroughput Impaired DNA demethylation of C/EBP sites causes premature aging 否 Premature ageing MEF E_01_0422 WGBS-seq,Oil Red O staining,RNA isolation,cDNA synthesis,qPCR,RNA-seq,RNA expression microarrays,ChIP,ChIP-seq,NG Capture-C,Methylation-sensitive PCR,Hematoxylin and eosin (H&E) staining,SA-β-Gal staining,Luciferase reporter assays,Co-IP,immunoblotting,Immunostaining Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers and, cooperatively with ING1, promotes local DNA demethylation via long-range chromatin loops to permit C/EBPβ recruitment. The results indicate that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process. Our study suggests a causal nexus between DNA demethylation, metabolism, and organismal aging. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers and, cooperatively with ING1, promotes local DNA demethylation via long-range chromatin loops to permit C/EBPβ recruitment. The results indicate that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process. Our study suggests a causal nexus between DNA demethylation, metabolism, and organismal aging. Immunohistochemical staining Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers and, cooperatively with ING1, promotes local DNA demethylation via long-range chromatin loops to permit C/EBPβ recruitment. The results indicate that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process. Our study suggests a causal nexus between DNA demethylation, metabolism, and organismal aging. WGBS-seq,Oil Red O staining,RNA isolation,cDNA synthesis,qPCR,RNA-seq,RNA expression microarrays,ChIP,ChIP-seq,NG Capture-C,Methylation-sensitive PCR,Hematoxylin and eosin (H&E) staining,SA-β-Gal staining,Luciferase reporter assays,Co-IP,immunoblotting,Immunostaining ING1 Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers and, cooperatively with ING1, promotes local DNA demethylation via long-range chromatin loops to permit C/EBPβ recruitment. The results indicate that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process. Our study suggests a causal nexus between DNA demethylation, metabolism, and organismal aging. 29883697 chr11 47266314 47268314 MADD The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia. human Nervous High+Lowthroughput Integrative analysis of genome-wide association study and brain region related enhancer maps identifies biological pathways for insomnia 否 insomnia neuronal stem cell E_01_0423 GWAS The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia. Immunohistochemical staining The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia. GWAS MADD,PPP2R3C,CASP9,PLEKHM2 The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia.;The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia.;The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia.;The chromosomal enhancer maps of 6 brain regions were then aligned with the GWAS summary data to obtain the association testing results of enhancer regions for insomnia. Gene prioritization, tissue/cell and pathway enrichment analysis were implemented by Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) tool. We identified multiple cross-brain regions or brain-region specific prioritized genes for insomnia, such as MADD (P = .0013 in angular gyrus), PPP2R3C (P = .0319 in cingulate gyrus), CASP9 (P = .0066 in angular gyrus and P = .0278 in hippocampus middle), PLEKHM2 (P = .0032 in angular gyrus, P = .0052 in anterior caudate, P = .0385 in cingulate gyrus and P = .0011 in inferior temporal lobe). This study also detected a group of insomnia associated biological pathways within multiple or specific brain regions, such as REACTOME_SIGNALING_BY_NOTCH and KEGG_GLYCEROPHOSPHOLIPID_METABOLISM. Our results showed that insomnia associated genes were significantly enriched in neural stem cells. Our results highlight a set of potential points, particularly neural stem cells, for subsequent biological studies for insomnia. 29882899 chr8 127732924 127734924 MYC Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation. human Colon High+Lowthroughput Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers 否 Other HCT-116 E_01_0424 PCR,Luciferase Reporter Assay,Real Time qPCR,Genome Editing,ChIP-Seq, Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation. Immunohistochemical staining Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation. PCR,Luciferase Reporter Assay,Real Time qPCR,Genome Editing,ChIP-Seq, MYC Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation. 29881302 chr7 27736725 27738725 TAX1BP1 We describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1, and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation. human Colon High+Lowthroughput Tumor necrosis factor α-induced protein 3 (A20) is dysregulated in pediatric Crohn disease 否 Pediatric inflammatory bowel disease (IBD) T-84 E_01_0425 Total RNA extraction,reverse transcription PCR,Cytokine analysis,Immunofluorescence microscopy,ELISA, We describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1, and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1, and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation. Immunohistochemical staining We describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1, and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation. Total RNA extraction,reverse transcription PCR,Cytokine analysis,Immunofluorescence microscopy,ELISA, TAX1BP1 We describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1, and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation. 29880601 chr12 7916539 7918539 SLC2A3 Finally, we investigated expression of the SLC2A3 and SLC2A14 genes, adjacently positioned to the eRNA07573 locus,in eRNA07573 KO cells. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection. human connective High+Lowthroughput Diminished nuclear RNA decay upon Salmonella infection upregulates antibacterial noncoding RNAs 否 Salmonella infection HeLa E_01_0426 transfection,RT–qPCR,siRNA,Immunoblotting,FISH,immunocytochemistry,Northern blot Finally, we investigated expression of the SLC2A3 and SLC2A14 genes, adjacently positioned to the eRNA07573 locus,in eRNA07573 KO cells. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, we investigated expression of the SLC2A3 and SLC2A14 genes, adjacently positioned to the eRNA07573 locus,in eRNA07573 KO cells. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection. Immunohistochemical staining Finally, we investigated expression of the SLC2A3 and SLC2A14 genes, adjacently positioned to the eRNA07573 locus,in eRNA07573 KO cells. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection. transfection,RT–qPCR,siRNA,Immunoblotting,FISH,immunocytochemistry,Northern blot SLC2A3 SOCS3 Finally, we investigated expression of the SLC2A3 and SLC2A14 genes, adjacently positioned to the eRNA07573 locus,in eRNA07573 KO cells. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection. Finally, we investigated expression of the SLC2A3 and SLC2A14 genes, adjacently positioned to the eRNA07573 locus,in eRNA07573 KO cells. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components, RRP6 and MTR4, dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs, NEAT1v2, or eRNA07573 in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense. Our results highlight a fundamental role for regulated degradation of nuclear RNA in the response to pathogenic infection. 29879032 chr14 51429786 51431786 Ang2 Initially, we found that BAY11-7082 inhibited NF-κB expression in a concentration-dependent manner. According to the findings of MTT assay and flow cytometry, we understood that RA-HFLS treated by BAY11-7082 (an inhibitor of NF-κB), the inhibition of NF-κB pathway, suppressed RA-HFLS proliferation and induced RA-HFLS apoptosis in a concentration and time-dependent manner. Furthermore, RA-HFLS treated by BAY11-7082 presented decreased VEGF, Ang1 and Ang2 expressions in a concentration-dependent manner.The study concluded that inhibition of NF-κB pathway induced cell apoptosis and suppressed proliferation and angiogenesis of RA-HFLS, which could serve as a novel target in the treatment of RA. mouse High+Lowthroughput Inhibition of NF-κB signaling pathway induces apoptosis and suppresses proliferation and angiogenesis of human fibroblast-like synovial cells in rheumatoid arthritis 否 Rheumatoid arthritis (RA) HFLS cell E_01_0427 MTT,Flow cytometry,Western blot Initially, we found that BAY11-7082 inhibited NF-κB expression in a concentration-dependent manner. According to the findings of MTT assay and flow cytometry, we understood that RA-HFLS treated by BAY11-7082 (an inhibitor of NF-κB), the inhibition of NF-κB pathway, suppressed RA-HFLS proliferation and induced RA-HFLS apoptosis in a concentration and time-dependent manner. Furthermore, RA-HFLS treated by BAY11-7082 presented decreased VEGF, Ang1 and Ang2 expressions in a concentration-dependent manner.The study concluded that inhibition of NF-κB pathway induced cell apoptosis and suppressed proliferation and angiogenesis of RA-HFLS, which could serve as a novel target in the treatment of RA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Initially, we found that BAY11-7082 inhibited NF-κB expression in a concentration-dependent manner. According to the findings of MTT assay and flow cytometry, we understood that RA-HFLS treated by BAY11-7082 (an inhibitor of NF-κB), the inhibition of NF-κB pathway, suppressed RA-HFLS proliferation and induced RA-HFLS apoptosis in a concentration and time-dependent manner. Furthermore, RA-HFLS treated by BAY11-7082 presented decreased VEGF, Ang1 and Ang2 expressions in a concentration-dependent manner.The study concluded that inhibition of NF-κB pathway induced cell apoptosis and suppressed proliferation and angiogenesis of RA-HFLS, which could serve as a novel target in the treatment of RA. Immunohistochemical staining Initially, we found that BAY11-7082 inhibited NF-κB expression in a concentration-dependent manner. According to the findings of MTT assay and flow cytometry, we understood that RA-HFLS treated by BAY11-7082 (an inhibitor of NF-κB), the inhibition of NF-κB pathway, suppressed RA-HFLS proliferation and induced RA-HFLS apoptosis in a concentration and time-dependent manner. Furthermore, RA-HFLS treated by BAY11-7082 presented decreased VEGF, Ang1 and Ang2 expressions in a concentration-dependent manner.The study concluded that inhibition of NF-κB pathway induced cell apoptosis and suppressed proliferation and angiogenesis of RA-HFLS, which could serve as a novel target in the treatment of RA. MTT,Flow cytometry,Western blot Ang2 Initially, we found that BAY11-7082 inhibited NF-κB expression in a concentration-dependent manner. According to the findings of MTT assay and flow cytometry, we understood that RA-HFLS treated by BAY11-7082 (an inhibitor of NF-κB), the inhibition of NF-κB pathway, suppressed RA-HFLS proliferation and induced RA-HFLS apoptosis in a concentration and time-dependent manner. Furthermore, RA-HFLS treated by BAY11-7082 presented decreased VEGF, Ang1 and Ang2 expressions in a concentration-dependent manner.The study concluded that inhibition of NF-κB pathway induced cell apoptosis and suppressed proliferation and angiogenesis of RA-HFLS, which could serve as a novel target in the treatment of RA. 29877106 chr10 24788525 24790525 Arg1 PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage. mouse lymphoid High+Lowthroughput Polysaccharides from Citrus grandis associate with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophages 否 chronic pharyngitis macrophage E_01_0428 Western blot,Enzyme-linked immunosorbent assay(ELISA),RT-PCR PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage. Immunohistochemical staining PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage. Western blot,Enzyme-linked immunosorbent assay(ELISA),RT-PCR Arg1,Mrc1 IRF1,IRF5 PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage.;PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage. PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage.;PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage. 29876014 chr18 63121048 63123048 BCL2 Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine. human Nervous High+Lowthroughput Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia 是 Acute promyelocytic leukemia (APL) promyelocyte E_01_0429 NGS,ChIP,RNA extraction,RT-PCR,Whole-genome bisulfite sequencing(WGBS),RNA-seq Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine. Immunohistochemical staining Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine. NGS,ChIP,RNA extraction,RT-PCR,Whole-genome bisulfite sequencing(WGBS),RNA-seq AK2 BCL2 Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine. Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs. Epigenetic comparison with low/intermediate-risk APLs and AMLs revealed hrAPL-specific patterns of histone acetylation and DNA methylation, suggesting these could be further developed into markers for clinical identification. The epigenetic drug MC2884, a newly generated general HAT/EZH2 inhibitor, induces apoptosis of high-risk APL blasts and reshapes their epigenomes by targeting both active and repressive marks. Together, our analysis uncovers distinctive epigenome signatures of hrAPL patients, and provides proof of concept for use of epigenome profiling coupled to epigenetic drugs to 'personalize' precision medicine. 29875794 chrX 67541120 67543120 AR To find relevant epigenetic signatures enriched at the ARA-lincRNAs' transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells. human Myotome High+Lowthroughput Chromatin Landscape Distinguishes the Genomic Loci of Hundreds of Androgen-Receptor-Associated LincRNAs From the Loci of Non-associated LincRNAs 否 LNCaP E_01_0430 RNA-seq,RIP-Seq,RT-qPCR,Reverse Transcription PCR,GSEA,DNAseI Datasets To find relevant epigenetic signatures enriched at the ARA-lincRNAs' transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To find relevant epigenetic signatures enriched at the ARA-lincRNAs' transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells. Immunohistochemical staining To find relevant epigenetic signatures enriched at the ARA-lincRNAs' transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells. RNA-seq,RIP-Seq,RT-qPCR,Reverse Transcription PCR,GSEA,DNAseI Datasets TUBA1C AR To find relevant epigenetic signatures enriched at the ARA-lincRNAs' transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells. To find relevant epigenetic signatures enriched at the ARA-lincRNAs' transcription start sites (TSSs) we used a machine learning approach and identified that the ARA-lincRNA genomic loci in LNCaP cells are significantly enriched with epigenetic marks that are characteristic of in cis enhancer RNA regulators, and that the H3K27ac mark of active enhancers is conspicuously enriched at the TSS of ARA-lincRNAs adjacent to androgen-activated protein-coding genes. In addition, LNCaP topologically associating domains (TADs) that comprise chromatin regions with ARA-lincRNAs exhibit transcription factor contents, epigenetic marks and gene transcriptional activities that are significantly different from TADs not containing ARA-lincRNAs. This work highlights the possible involvement of hundreds of lincRNAs working in synergy with the AR on the genome-wide androgen-induced gene regulatory program in prostate cells. 29875318 chr19 30520129 30522129 Dkk1 In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue. mouse connective High+Lowthroughput Sclerostin neutralization unleashes the osteoanabolic effects of Dkk1 inhibition 否 Osteoporosis osteocyte E_01_0431 DXA,μCT,pQCT,Histology,transgenic mice,ELISA, In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue. Immunohistochemical staining In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue. DXA,μCT,pQCT,Histology,transgenic mice,ELISA, Dkk1,Dmp1,SOST,LRP5 In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue.;In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue.;In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue.;In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue. 29874879 chr14 74473514 74475514 NPC2 Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function. human connective High+Lowthroughput Niemann-Pick Type C2 Protein Regulates Free Cholesterol Accumulation and Influences Hepatic Stellate Cell Proliferation and Mitochondrial Respiration Function 否 hepatic fibrosis HSC-T6 cell E_01_0432 Western Blot,Real-Time PCR,Seahorse Assay Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function. Immunohistochemical staining Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function. Western Blot,Real-Time PCR,Seahorse Assay NPC2 TLR4 Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function. Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function. 29871881 chr4 102498539 102500539 NFKB1 Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome. human High+Lowthroughput Human Enhancers Harboring Specific Sequence Composition, Activity, and Genome Organization Are Linked to the Immune Response 是 Other E_01_0433 Hi-C,RELA ChIP-seq, DNA seq Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome. Immunohistochemical staining Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome. Hi-C,RELA ChIP-seq, DNA seq BACH2 NFKB1,REL,RELA,BPTF Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome. Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.;Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.;Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.;Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome. 29869821 chr2 15587927 15589927 DDX1 These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer. human Colon High+Lowthroughput DEAD box protein DDX1 promotes colorectal tumorigenesis through transcriptional activation of the LGR5 gene 否 Colorectal neoplasms LoVo cell E_01_0434 CRISPR / Cas9,knockdown,Quantitative RT‐PCR,Western blot,Luciferase reporter assay,Immunohistochemistry, Immunofluorescence analysis,ChIP These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer. Immunohistochemical staining These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer. CRISPR / Cas9,knockdown,Quantitative RT‐PCR,Western blot,Luciferase reporter assay,Immunohistochemistry, Immunofluorescence analysis,ChIP DDX1 LGR5,SOX2 These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer. These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer.;These results suggest that LGR5 is a critical effector of DDX1 in colorectal cancer cells. The DDX1-LGR5 axis could be a new drug target for this type of malignant cancer. 29866822 chr4 54654583 54656583 KIT Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease. human Kidney High+Lowthroughput Gastrointestinal stromal tumor enhancers support a transcription factor network predictive of clinical outcome 否 Gastrointestinal stromal tumor (GIST) 293FT E_01_0435 Transfection,RNA-Seq,ATAC-seq,ChIP-Seq,Quantitative RT-PCR,Cloning,CRISPR Assays,Immunoblotting Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease. Immunohistochemical staining Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease. Transfection,RNA-Seq,ATAC-seq,ChIP-Seq,Quantitative RT-PCR,Cloning,CRISPR Assays,Immunoblotting KIT,PDGFRA,HAND1 Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease.;Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease.;Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease. 29864144 chrX 71530253 71532253 OGT The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability. human Mammary High+Lowthroughput Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells 否 mammary cancer MCF10A E_01_0436 RT-PCR,RNA isolation,Western blot,Chromatin immunoprecipitation assay(CHIP),Migration/invasion assay, The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability. Immunohistochemical staining The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability. RT-PCR,RNA isolation,Western blot,Chromatin immunoprecipitation assay(CHIP),Migration/invasion assay, OGT,EZH2,FOXA1,FOXC1,SUZ12 The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability.;The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability.;The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability.;The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability.;The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability. 29858072 chr5 138462604 138464604 EGR1 Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells. human Nervous High+Lowthroughput Inflammatory-Related P62 Triggers Malignant Transformation of Mesenchymal Stem Cells through the Cascade of CUDR-CTCF-IGFII-RAS Signaling 否 Inflammation, tumour HBMMSCs cell E_01_0437 Transfection,RT-PCR,Western Blot,GST Pull-Down,Super-EMSA,ChIP,Co-IP,ChIP-3C/ChIP-Loop Assays,Cells Proliferation CCK8 Assay,Soft-Agar Colony Formation Assay,Xenograft Transplantation In Vivo,Histological Analysis Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells. Immunohistochemical staining Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells. Transfection,RT-PCR,Western Blot,GST Pull-Down,Super-EMSA,ChIP,Co-IP,ChIP-3C/ChIP-Loop Assays,Cells Proliferation CCK8 Assay,Soft-Agar Colony Formation Assay,Xenograft Transplantation In Vivo,Histological Analysis EGR1,TLR4,CTCF Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells.;Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells.;Mechanistically, we reveal P62 enhances IGFII transcriptional activity through forming IGFII promoter-enhancer chromatin loop and increasing METTL3 occupancy on IGFII 3' UTR and enhances H-Ras overexpression by harboring inflammation-related factors, e.g., TNFR1, CLYD, EGR1, NFκB, TLR4, and PPARγ. Furthermore, the P62 cooperates with TNF-α to promote malignant transformation of mesenchymal stem cells. These findings, for the first time, provide insight into the positive role that P62 plays in malignant transformation of mesenchymal stem cells and reveal a novel link between P62 and the inflammation factors in mesenchymal stem cells. 29853604 chr4 186066731 186068731 TLR3 This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. human connective High+Lowthroughput Helicase-Driven Activation of NFκB-COX2 Pathway Mediates the Immunosuppressive Component of dsRNA-Driven Inflammation in the Human Tumor Microenvironment 否 Inflammation, cancer C0135C E_01_0438 Western blot,Image flow analysis,Immunofluorescence,Phospho-CREB activation,RT-PCR,ELISA,chemotaxis assays, This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. Immunohistochemical staining This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. Western blot,Image flow analysis,Immunofluorescence,Phospho-CREB activation,RT-PCR,ELISA,chemotaxis assays, TLR3,CCL22,CXCL12 TRAF3,IRF3,CXCL10,IL10 This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. ;This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. ;This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. ;This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. ;This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. ;This study characterizes two different poly-I:C-induced signaling pathways in their induction of immunostimulatory and suppressive factors and suggests improved ways to reprogram the TME to enhance the antitumor efficacy of immunotherapies. 29853569 chr3 97917797 97919797 Notch2 We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling. mouse Myotome High+Lowthroughput Notch2 and Proteomic Signatures in Mouse Neointimal Lesion Formation 否 Neointimal lesions VSMC E_01_0439 PCR, immunohistochemical staining,Vessel morphometric analysis,immunostaining,Transgenic mice, We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling. Immunohistochemical staining We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling. PCR, immunohistochemical staining,Vessel morphometric analysis,immunostaining,Transgenic mice, Notch2,Notch1 We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling.;We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling. 29851165 chr11 32385307 32387307 WT1 Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF-β1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF-β1, which could contribute to podocyte injury. human High+Lowthroughput TGF-β1 alters DNA methylation levels in promoter and enhancer regions of the WT1 gene in human podocytes 否 Wilms tumor 1 (WT1) AB8/13 E_01_0440 ChIP-seq,Quantitative methylation-specific PCR,Quantitative methylation-specific PCR,Western blot, Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF-β1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF-β1, which could contribute to podocyte injury. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF-β1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF-β1, which could contribute to podocyte injury. Immunohistochemical staining Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF-β1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF-β1, which could contribute to podocyte injury. ChIP-seq,Quantitative methylation-specific PCR,Quantitative methylation-specific PCR,Western blot, WT1 Our data suggest that the methylation pattern of the WT1 promoter and enhancers in human podocytes are distinctive from those in HK2. Furthermore, TGF-β1 alters the methylation levels of the WT1 promoter and enhancers in human podocytes. This modification may be relevant to the attenuation of WT1 by TGF-β1, which could contribute to podocyte injury. 29848731 chr7 148804383 148806383 EZH2 EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. human Lung High+Lowthroughput Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer 否 Small cell lung cancer (SCLC) NSCC cell E_01_0441 Immunohistochemical analyses, EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Immunohistochemical staining EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Immunohistochemical analyses, EZH2 EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. 29845218 chr16 4254258 4256258 TFAP4 In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC. human Gastric High+Lowthroughput Elevated TFAP4 regulates lncRNA TRERNA1 to promote cell migration and invasion in gastric cancer 否 gastric cancer AGS, SGC‑7901 and BGC‑823 E_01_0442 Reverse transcription‑quantitative PCR (RT‑qPCR),transfection,Cell migration and invasion assays,Luciferase reporter assay,Chromatin immunoprecipitation (ChIP) assay In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC. Immunohistochemical staining In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC. Reverse transcription‑quantitative PCR (RT‑qPCR),transfection,Cell migration and invasion assays,Luciferase reporter assay,Chromatin immunoprecipitation (ChIP) assay TRERNA1 TFAP4 In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC. In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC. 29842805 chr15 99562745 99564745 MEF2A The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases. human Epithelial High+Lowthroughput The MEF2A and MEF2D function as scaffold proteins that interact with HDAC1 or p300 in SOD3 expression in THP-1 cells 否 Neoplasm, vascular disease THP-1 E_01_0443 Western blot,Chromatin immunoprecipitation (ChIP) assay,RT-PCR,transfection,Immunoprecipitation (IP),small interfering RNA transfection The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases. Immunohistochemical staining The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases. Western blot,Chromatin immunoprecipitation (ChIP) assay,RT-PCR,transfection,Immunoprecipitation (IP),small interfering RNA transfection MEF2D,SOD3 MEF2A,HDAC1 The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases.;The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases. The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases.;The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells. On the other hand, the dissociation of HDAC1 from the SOD3 promoter region and the enrichment of p300, a histone acetyltransferase (HAT), within that region were observed in TPA-induced THP-1 cells. Myocyte enhancer factor 2 (MEF2) functions as a scaffold protein that interacts with histone deacetylases (HDAC) or HAT and regulates gene expression. The present results showed that the MEF2A and MEF2D function as mediators for TPA-elicited SOD3 expression by interacting with HDAC or p300. Additionally, the knockdown of MEF2A or MEF2D in human skin fibroblasts suppressed SOD3 expression at the mRNA and protein levels. Our results provide an insight into epigenetic regulation of redox gene expression, and may ultimately contribute to suppressing the progression of tumours and vascular diseases. 29813070 chr10 80968670 80970670 Zbtb7a Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression. mouse Nervous High+Lowthroughput Zbtb7a is a transducer for the control of promoter accessibility by NF-kappa B and multiple other transcription factors 否 Other 3T3 E_01_0444 Zbtb7a knockdown,quantitative real-time PCR,ChIP,ChIP-seq,DHS sequencing,Reporter assays,BiFC,GST pull-down,MS,Analysis of genomic datasets Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression. Immunohistochemical staining Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression. Zbtb7a knockdown,quantitative real-time PCR,ChIP,ChIP-seq,DHS sequencing,Reporter assays,BiFC,GST pull-down,MS,Analysis of genomic datasets Zbtb7a Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression. 29808619 chr17 34252611 34254611 CCL2 AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling. human Prostate High+Lowthroughput Loss of androgen receptor signaling in prostate cancer-associated fibroblasts (CAFs) promotes CCL2- and CXCL8-mediated cancer cell migration 否 Prostate cancer (PCA) LNCaPs、cwr1 E_01_0445 ChiP-seq,ChIP-seq,western blot,immunohistochemistry (IHC) AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling. Immunohistochemical staining AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling. ChiP-seq,ChIP-seq,western blot,immunohistochemistry (IHC) CCL2,CXCL8,AR AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling.;AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling.;AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling. 29806631 chr4 106918996 106920996 DKK2 In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis. human Facet joint High+Lowthroughput Altered Wnt and NF-κB Signaling in Facet Joint Osteoarthritis: Insights from RNA Deep Sequencing 否 Facet joint osteoarthritis, lumbar spine osteoarthritis mutant lymphoma cell E_01_0446 RNA-seq,Bioinformatic analysis,qRT-PCR, In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis. Immunohistochemical staining In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis. RNA-seq,Bioinformatic analysis,qRT-PCR, DKK2,TCF7,CCL4,CCL4L2 SOX17,MYC,CAMK2A,LEF1 In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.;In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.;In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.;In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis. In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.;In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.;In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.;In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis. 29805666 chr7 148804346 148806346 EZH2 Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma. human Endometrial cancer High+Lowthroughput Enhancer of zeste homolog 2 blockade by RNA interference is implicated with inhibited proliferation, invasion and promoted apoptosis in endometrial carcinoma 否 Endometrial cancer (EC) monoblast E_01_0447 Western blot,EZH2 small interfering (si)RNA transfection,Quantitative reverse transcription‑polymerase chain reaction (RT‑qPCR) analysis,In vitro cell proliferation assay,Annexin V/propidium iodide (PI) staining,Matrigel invasion assay,immunohistochemical analysis Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma. Immunohistochemical staining Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma. Western blot,EZH2 small interfering (si)RNA transfection,Quantitative reverse transcription‑polymerase chain reaction (RT‑qPCR) analysis,In vitro cell proliferation assay,Annexin V/propidium iodide (PI) staining,Matrigel invasion assay,immunohistochemical analysis EZH2,BCL2 Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma.;Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma. 29805099 chr20 50188232 50190232 CEBPB Collectively, tumor glycolysis orchestrates a molecular network of the AMPK-ULK1, autophagy, and CEBPB pathways to affect MDSCs and maintain tumor immunosuppression. human Mammary High+Lowthroughput Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer 否 Triple negative breast cancer (TNBC) 4T1 E_01_0448 Short Pairpin RNAs (shRNA),Small Interfering RNA (siRNA),Genetic Knockout,Western Blot,RNA Extraction,Reverse Transcription,Real-Time Polymerase Chain Reaction,Flow Cytometry Analysis (FACS),Immunofluorescence Staining,Metabolic Assay,Bioinformatics Analysis Collectively, tumor glycolysis orchestrates a molecular network of the AMPK-ULK1, autophagy, and CEBPB pathways to affect MDSCs and maintain tumor immunosuppression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, tumor glycolysis orchestrates a molecular network of the AMPK-ULK1, autophagy, and CEBPB pathways to affect MDSCs and maintain tumor immunosuppression. Immunohistochemical staining Collectively, tumor glycolysis orchestrates a molecular network of the AMPK-ULK1, autophagy, and CEBPB pathways to affect MDSCs and maintain tumor immunosuppression. Short Pairpin RNAs (shRNA),Small Interfering RNA (siRNA),Genetic Knockout,Western Blot,RNA Extraction,Reverse Transcription,Real-Time Polymerase Chain Reaction,Flow Cytometry Analysis (FACS),Immunofluorescence Staining,Metabolic Assay,Bioinformatics Analysis CEBPB Collectively, tumor glycolysis orchestrates a molecular network of the AMPK-ULK1, autophagy, and CEBPB pathways to affect MDSCs and maintain tumor immunosuppression. 29802990 chr15 102311121 102313121 Sp1 We identified two alternative nine-SNPs haplotypes strictly linked to the allele *1 and *2 of hs1.2, that could be used as markers to further investigate the region and associations to pathology. Finally, we identified two haplotypes, namely E2A1 and E2A2, that strongly support the hypothesis of a relevant effect of the rs35216181 in the onset of Psoriasis when the *2 allele is present. mouse lymphoid High+Lowthroughput Association between Psoriasis and haplotypes of the IgH 3' Regulatory Region 1 是 rs35216181,rs373084296 Autoimmune disease, psoriasis T cell E_01_0449 nested-PCR We identified two alternative nine-SNPs haplotypes strictly linked to the allele *1 and *2 of hs1.2, that could be used as markers to further investigate the region and associations to pathology. Finally, we identified two haplotypes, namely E2A1 and E2A2, that strongly support the hypothesis of a relevant effect of the rs35216181 in the onset of Psoriasis when the *2 allele is present. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified two alternative nine-SNPs haplotypes strictly linked to the allele *1 and *2 of hs1.2, that could be used as markers to further investigate the region and associations to pathology. Finally, we identified two haplotypes, namely E2A1 and E2A2, that strongly support the hypothesis of a relevant effect of the rs35216181 in the onset of Psoriasis when the *2 allele is present. Immunohistochemical staining We identified two alternative nine-SNPs haplotypes strictly linked to the allele *1 and *2 of hs1.2, that could be used as markers to further investigate the region and associations to pathology. Finally, we identified two haplotypes, namely E2A1 and E2A2, that strongly support the hypothesis of a relevant effect of the rs35216181 in the onset of Psoriasis when the *2 allele is present. nested-PCR Sp1 We identified two alternative nine-SNPs haplotypes strictly linked to the allele *1 and *2 of hs1.2, that could be used as markers to further investigate the region and associations to pathology. Finally, we identified two haplotypes, namely E2A1 and E2A2, that strongly support the hypothesis of a relevant effect of the rs35216181 in the onset of Psoriasis when the *2 allele is present. 29799396 chr12 6784343 6786343 CD4 Employing a combined phenotypic and transcriptomic approach we disclosed a Th1/Th17 phenotype as well as innate and adaptive functions of CD4+CD8+ double-positive T-cells in GPA. human connective High+Lowthroughput Circulating CD4+CD8+ double-positive T-cells display features of innate and adaptive immune function in granulomatosis with polyangiitis 否 Granulomatosis with polyangiitis (GPA) whole blood cell E_01_0450 Flow cytometric analysis,Transcriptome,biological database analysis Employing a combined phenotypic and transcriptomic approach we disclosed a Th1/Th17 phenotype as well as innate and adaptive functions of CD4+CD8+ double-positive T-cells in GPA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Employing a combined phenotypic and transcriptomic approach we disclosed a Th1/Th17 phenotype as well as innate and adaptive functions of CD4+CD8+ double-positive T-cells in GPA. Immunohistochemical staining Employing a combined phenotypic and transcriptomic approach we disclosed a Th1/Th17 phenotype as well as innate and adaptive functions of CD4+CD8+ double-positive T-cells in GPA. Flow cytometric analysis,Transcriptome,biological database analysis CD4 Employing a combined phenotypic and transcriptomic approach we disclosed a Th1/Th17 phenotype as well as innate and adaptive functions of CD4+CD8+ double-positive T-cells in GPA. 29797095 chr3 133743341 133745341 TF We present a workflow, integrating epigenomics and topologically associating domain data, aimed at discovering trait-associated SNP pairs from GWAS where neither SNP achieved independent genome-wide significance. Each analyzed SNP pair consists of one SNP in a putative active enhancer and another SNP in a putative physically interacting gene promoter in a trait-relevant tissue. As a proof-of-principle case study, we used this approach to identify focused collections of SNP pairs that we analyzed in three independent Type 2 diabetes (T2D) GWAS. This approach led us to discover 35 significant SNP pairs, encompassing both novel signals and signals for which we have found orthogonal support from other sources. Nine of these pairs are consistent with eQTL results, two are consistent with our own capture C experiments, and seven involve signals supported by recent T2D literature. human Liver High+Lowthroughput Leveraging epigenomics and contactomics data to investigate SNP pairs in GWAS 是 rs76024800,rs7577213 Type 2 diabetes (T2D) HEPG2 E_01_0451 GWAS,DNase-Seq,ATAC-Seq, We present a workflow, integrating epigenomics and topologically associating domain data, aimed at discovering trait-associated SNP pairs from GWAS where neither SNP achieved independent genome-wide significance. Each analyzed SNP pair consists of one SNP in a putative active enhancer and another SNP in a putative physically interacting gene promoter in a trait-relevant tissue. As a proof-of-principle case study, we used this approach to identify focused collections of SNP pairs that we analyzed in three independent Type 2 diabetes (T2D) GWAS. This approach led us to discover 35 significant SNP pairs, encompassing both novel signals and signals for which we have found orthogonal support from other sources. Nine of these pairs are consistent with eQTL results, two are consistent with our own capture C experiments, and seven involve signals supported by recent T2D literature. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We present a workflow, integrating epigenomics and topologically associating domain data, aimed at discovering trait-associated SNP pairs from GWAS where neither SNP achieved independent genome-wide significance. Each analyzed SNP pair consists of one SNP in a putative active enhancer and another SNP in a putative physically interacting gene promoter in a trait-relevant tissue. As a proof-of-principle case study, we used this approach to identify focused collections of SNP pairs that we analyzed in three independent Type 2 diabetes (T2D) GWAS. This approach led us to discover 35 significant SNP pairs, encompassing both novel signals and signals for which we have found orthogonal support from other sources. Nine of these pairs are consistent with eQTL results, two are consistent with our own capture C experiments, and seven involve signals supported by recent T2D literature. Immunohistochemical staining We present a workflow, integrating epigenomics and topologically associating domain data, aimed at discovering trait-associated SNP pairs from GWAS where neither SNP achieved independent genome-wide significance. Each analyzed SNP pair consists of one SNP in a putative active enhancer and another SNP in a putative physically interacting gene promoter in a trait-relevant tissue. As a proof-of-principle case study, we used this approach to identify focused collections of SNP pairs that we analyzed in three independent Type 2 diabetes (T2D) GWAS. This approach led us to discover 35 significant SNP pairs, encompassing both novel signals and signals for which we have found orthogonal support from other sources. Nine of these pairs are consistent with eQTL results, two are consistent with our own capture C experiments, and seven involve signals supported by recent T2D literature. GWAS,DNase-Seq,ATAC-Seq, TF We present a workflow, integrating epigenomics and topologically associating domain data, aimed at discovering trait-associated SNP pairs from GWAS where neither SNP achieved independent genome-wide significance. Each analyzed SNP pair consists of one SNP in a putative active enhancer and another SNP in a putative physically interacting gene promoter in a trait-relevant tissue. As a proof-of-principle case study, we used this approach to identify focused collections of SNP pairs that we analyzed in three independent Type 2 diabetes (T2D) GWAS. This approach led us to discover 35 significant SNP pairs, encompassing both novel signals and signals for which we have found orthogonal support from other sources. Nine of these pairs are consistent with eQTL results, two are consistent with our own capture C experiments, and seven involve signals supported by recent T2D literature. 29794985 chr17 17678780 17680780 RAI1 These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. human Nervous High+Lowthroughput A Rare De Novo RAI1 Gene Mutation Affecting BDNF-Enhancer-Driven Transcription Activity Associated with Autism and Atypical Smith-Magenis Syndrome Presentation 是 Autism, atypical Smith Magenis syndrome Neuro-2a E_01_0452 AMPure,PCR,Western Blot,Immunofluorescence Analysis,Reporter Gene Assays,RNA-Seq,transfection of Neuro-2a cells These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. Immunohistochemical staining These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. AMPure,PCR,Western Blot,Immunofluorescence Analysis,Reporter Gene Assays,RNA-Seq,transfection of Neuro-2a cells RAI1 BDNF These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. These results suggest a likely contribution of RAI1, either alone or in combination of other factors, to social behavior and reinforce the RAI1 gene as a candidate gene in patients with autistic manifestations or social behavioral abnormalities. 29794473 chr8 19899275 19901275 LPL During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs. human adipose High+Lowthroughput MiR-27b Impairs Adipocyte Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting LPL 否 Other hASCs E_01_0453 Double Dual Luciferase Reporter Assay,qRT-PCR,western blot,cellular immunofluorescence,oil red O staining assay,Cell transfection During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs. Immunohistochemical staining During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs. Double Dual Luciferase Reporter Assay,qRT-PCR,western blot,cellular immunofluorescence,oil red O staining assay,Cell transfection LPL During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs. 29792826 chr4 56905265 56907265 REST Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations. human High+Lowthroughput Fast-Evolving Human-Specific Neural Enhancers Are Associated with Aging-Related Diseases 是 Alzheimer's disease, aging HEK293T E_01_0454 CRISPR/Cas9,chromatin immunoprecipitation sequencing,qRT-PCR,PCR, RNA-seq,transfection Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations. Immunohistochemical staining Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations. CRISPR/Cas9,chromatin immunoprecipitation sequencing,qRT-PCR,PCR, RNA-seq,transfection REST Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations. 29790264 chr11 32384629 32386629 WT1 These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. human lymphoid High+Lowthroughput Immune responses against tumour-associated antigen-derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients 否 Cholangiocarcinoma TILs E_01_0455 ELISPOT,PCR,real-time PCR,Immunotherapy These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. Immunohistochemical staining These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. ELISPOT,PCR,real-time PCR,Immunotherapy WT1,MUC5AC,GPC3,KIF20A EZH2 These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy.;These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy.;These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy.;These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. 29789713 chr1 47429569 47431569 FOXD2-AS1 Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. human High+Lowthroughput Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer 否 Gastric cancer (GC) BGC823 E_01_0456 GSEA,quantitative real-time PCR,transfection,Flow cytometry,Western blot,Immunohistochemistry(IHC),ChIRP,RIP,RNA pull-down assay,Cell proliferation assays,chromatin immunoprecipitation (ChIP) Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. Immunohistochemical staining Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. GSEA,quantitative real-time PCR,transfection,Flow cytometry,Western blot,Immunohistochemistry(IHC),ChIRP,RIP,RNA pull-down assay,Cell proliferation assays,chromatin immunoprecipitation (ChIP) FOXD2-AS1 EZH2 Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis. 29789597 chr6 31572755 31574755 TNF In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways. human lymphoid High+Lowthroughput Enhancer of zeste homolog 2-catalysed H3K27 trimethylation plays a key role in acute-on-chronic liver failure via TNF-mediated pathway 否 Acute phase chronic liver failure PBMC E_01_0457 Western blot,reverse transcription-PCR,cytokine analysis,Immunostaining,Histological analysis,Chromatin immunoprecipitation (ChIP) assays In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways. Immunohistochemical staining In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways. Western blot,reverse transcription-PCR,cytokine analysis,Immunostaining,Histological analysis,Chromatin immunoprecipitation (ChIP) assays CD68 TNF,EZH2 In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways. In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways.;In conclusion, EZH2 and H3K27me3 contributed to the pathogenesis of liver failure via triggering TNF and other indispensable proinflammatory cytokines. EZH2 was to modify H3K27me3 enrichment, as well as, activation of the downstream NF-κB and Akt signalling pathways. 29789579 chr14 75276080 75278080 FOS Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells. human Nervous High+Lowthroughput Endogenous authentic OCT4A proteins directly regulate FOS/AP-1 transcription in somatic cancer cells 否 Other 293T E_01_0458 CRISPR\Cas9,PCR,western blot,qRT-PCR,immunoprecipitation(IP),Immunostaining,immunoblotting,ChIP assays,ChIP-PCR,MS analysis,RNA-Seq,western blotting (WB) analysis Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells. Immunohistochemical staining Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells. CRISPR\Cas9,PCR,western blot,qRT-PCR,immunoprecipitation(IP),Immunostaining,immunoblotting,ChIP assays,ChIP-PCR,MS analysis,RNA-Seq,western blotting (WB) analysis FOS,POU5F1 Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells.;Taken together, we resolve the long-standing controversy and uncertainty in the field, and reveal a fundamental role of OCT4A protein in regulating FOS/AP-1 signaling-centered genes that mediate the adhesion, migration, and propagation of somatic cancer cells. 29789508 chr17 82075550 82077550 FASN Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation. human adipose High+Lowthroughput Dual Effects of Metformin on Adipogenic Differentiation of 3T3-L1 Preadipocyte in AMPK-Dependent and Independent Manners 否 Type 2 diabetes (T2D) 3T3-L1 E_01_0459 Oil Red O Staining,MTT assay,Quantitative Real-Time PCR,Western Blot Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation. Immunohistochemical staining Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation. Oil Red O Staining,MTT assay,Quantitative Real-Time PCR,Western Blot FASN Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation. 29785964 chr6 170551706 170553706 TBP In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. human High+Lowthroughput Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters 否 Other 293 cell E_01_0460 transfection,immunoblots,DNase I footprinting,EMSAs,In vitro transcription assay,ChIPs,Pull-down assay,ChIP-seq,ChIP-qPCRs In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. Immunohistochemical staining In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. transfection,immunoblots,DNase I footprinting,EMSAs,In vitro transcription assay,ChIPs,Pull-down assay,ChIP-seq,ChIP-qPCRs BRF2 TBP In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. 29783071 chr15 99562489 99564489 MEF2A Finally, the results of ChIP indicated that MEF2A occupied the promoter region of the Capn3 gene in rat denervated gastrocnemius muscle tissue. Based on these results, we proposed that MEF2A is a transcriptional regulator for Capn3 gene expression. human Gastrocnemius muscle High+Lowthroughput MEF2A regulates Calpain 3 expression in L6 myoblasts 否 Muscle wasting after reversible sciatic nerve injury L6 cell E_01_0461 Luciferase reporter assay,EMSA,PCR,Western Blot,qRT-PCR,immunocytochemistry,ChIP,siRNA treatment,Bioinformatics analysis,plasmid construction Finally, the results of ChIP indicated that MEF2A occupied the promoter region of the Capn3 gene in rat denervated gastrocnemius muscle tissue. Based on these results, we proposed that MEF2A is a transcriptional regulator for Capn3 gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, the results of ChIP indicated that MEF2A occupied the promoter region of the Capn3 gene in rat denervated gastrocnemius muscle tissue. Based on these results, we proposed that MEF2A is a transcriptional regulator for Capn3 gene expression. Immunohistochemical staining Finally, the results of ChIP indicated that MEF2A occupied the promoter region of the Capn3 gene in rat denervated gastrocnemius muscle tissue. Based on these results, we proposed that MEF2A is a transcriptional regulator for Capn3 gene expression. Luciferase reporter assay,EMSA,PCR,Western Blot,qRT-PCR,immunocytochemistry,ChIP,siRNA treatment,Bioinformatics analysis,plasmid construction Capn3 MEF2A Finally, the results of ChIP indicated that MEF2A occupied the promoter region of the Capn3 gene in rat denervated gastrocnemius muscle tissue. Based on these results, we proposed that MEF2A is a transcriptional regulator for Capn3 gene expression. Finally, the results of ChIP indicated that MEF2A occupied the promoter region of the Capn3 gene in rat denervated gastrocnemius muscle tissue. Based on these results, we proposed that MEF2A is a transcriptional regulator for Capn3 gene expression. 29779941 chr1 3066245 3068245 PRDM16 These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex. human Nervous High+Lowthroughput The Epigenetic State of PRDM16-Regulated Enhancers in Radial Glia Controls Cortical Neuron Position 否 Other HEK293 E_01_0462 RNA,Chromatin Immunoprecipitation,Native Chromatin Immunoprecipitation,Prdm16 and Pdzrn3 Knockdown,RNaseq Analysis,ChIP-Seq,Binding and Expression Target Analysis (BETA), These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex. Immunohistochemical staining These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex. RNA,Chromatin Immunoprecipitation,Native Chromatin Immunoprecipitation,Prdm16 and Pdzrn3 Knockdown,RNaseq Analysis,ChIP-Seq,Binding and Expression Target Analysis (BETA), PRDM16,PDZRN3 These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex.;These findings provide insights into how epigenetic control of transcriptional enhancers in radial glial determines the organization of the mammalian cerebral cortex. 29779861 chr19 42504265 42506265 CEACAM1 human Epithelial High+Lowthroughput HopQ impacts the integrin α5β1-independent NF-κB activation by Helicobacter pylori in CEACAM expressing cells 否 Peptic ulcer disease, gastric cancer HeLa cell E_01_0463 siRNA transfection,Immunofluorescence (IF),immunoblotting,immunoprecipitation,PCR Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Immunohistochemical staining siRNA transfection,Immunofluorescence (IF),immunoblotting,immunoprecipitation,PCR CEACAM1 29777912 chr19 15233026 15235026 BRD4 Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1. human connective High+Lowthroughput A super-enhancer maintains homeostatic expression of Regnase-1 否 Autoimmune diseases, cancer HEK293T E_01_0464 transfection,Quantitative RT-PCR,Western blot,CRISPR/Cas9 Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1. Immunohistochemical staining Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1. transfection,Quantitative RT-PCR,Western blot,CRISPR/Cas9 ZC3H12A BRD4,MED1 Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1. Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1.;Our result reveals a novel molecular mechanism by which a super-enhancer around the second intron regulates the expression of Regnase-1, and in turn maintains a desired level of Regnase-1. 29775615 chr4 87647723 87649723 DMP1 This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone. human connective High+Lowthroughput Extracellular matrix protein DMP1 suppresses osteogenic differentiation of Mesenchymal Stem Cells 否 Other mouse bone marrow cell E_01_0465 Immunofluorescence staining,Real-time PCR,Western blot,Analysis of histology This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone. Immunohistochemical staining This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone. Immunofluorescence staining,Real-time PCR,Western blot,Analysis of histology DMP1 This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone. 29775582 chr2 11479885 11481885 GREB1 "Collectively, these data suggest that the enhancer and promoter remain ""poised"" for transcription via their contacts with GBS1 and GBS2. Upon E2 induction, GBS1 and GBS2 disengage from the enhancer, allowing direct EPC for active transcription." human Epithelial High+Lowthroughput SRC-3 Coactivator Governs Dynamic Estrogen-Induced Chromatin Looping Interactions during Transcription 否 Other HeLa S3 E_01_0466 3C,Immunoblotting,Chromatin Reconstitution,Immunodepletion,3C-qPCR,qPCR "Collectively, these data suggest that the enhancer and promoter remain ""poised"" for transcription via their contacts with GBS1 and GBS2. Upon E2 induction, GBS1 and GBS2 disengage from the enhancer, allowing direct EPC for active transcription." Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq "Collectively, these data suggest that the enhancer and promoter remain ""poised"" for transcription via their contacts with GBS1 and GBS2. Upon E2 induction, GBS1 and GBS2 disengage from the enhancer, allowing direct EPC for active transcription." Immunohistochemical staining "Collectively, these data suggest that the enhancer and promoter remain ""poised"" for transcription via their contacts with GBS1 and GBS2. Upon E2 induction, GBS1 and GBS2 disengage from the enhancer, allowing direct EPC for active transcription." 3C,Immunoblotting,Chromatin Reconstitution,Immunodepletion,3C-qPCR,qPCR GREB1 "Collectively, these data suggest that the enhancer and promoter remain ""poised"" for transcription via their contacts with GBS1 and GBS2. Upon E2 induction, GBS1 and GBS2 disengage from the enhancer, allowing direct EPC for active transcription." 29774079 chr19 15825440 15827440 UCA1 These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-β-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer. human Mammary High+Lowthroughput "Long non-coding RNAs AC026904.1 and UCA1: a ""one-two punch"" for TGF-β-induced SNAI2 activation and epithelial-mesenchymal transition in breast cancer" 否 mammary cancer MDA-MB-231-luc-D3H2LN E_01_0467 ChIRP,microarray analysis,qPCR,Kaplan-Meier survival analysis,confocal laser microscopy,Western blot,chromosome conformation capture (3C),RNA purification (ChIRP), ChIP,luciferase reporter assay,transwell migration assay These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-β-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-β-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer. Immunohistochemical staining These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-β-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer. ChIRP,microarray analysis,qPCR,Kaplan-Meier survival analysis,confocal laser microscopy,Western blot,chromosome conformation capture (3C),RNA purification (ChIRP), ChIP,luciferase reporter assay,transwell migration assay UCA1 SNAI2 These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-β-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer. These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-β-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer. 29773854 chr12 102393392 102395392 IGF1 Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci. human Epithelial High+Lowthroughput Genome-wide haplotype association analysis of primary biliary cholangitis risk in Japanese 是 Primary biliary cholangitis (PBC) epithelial cell E_01_0468 ChIP-seq Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci. Immunohistochemical staining Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci. ChIP-seq UMAD1,TNFSF15 IGF1 Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci.;Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci. Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci. 29773832 chr3 133743689 133745689 TF Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets. human Epithelial High+Lowthroughput Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes 否 Pancreatic ductal adenocarcinoma (PDAC) subtype epithelial cell E_01_0469 RNA extraction,RNA-seq,ChIP-seq,SNP arrays analysis,siRNA transfection,qPCR Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets. Immunohistochemical staining Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets. RNA extraction,RNA-seq,ChIP-seq,SNP arrays analysis,siRNA transfection,qPCR TF IL6 Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets. 29772677 chrX 123856883 123858883 XIAP Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs. human Lung High+Lowthroughput Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4 否 A549 E_01_0470 Western Blot,Co-Immunoprecipitation,Cell Cycle Analysis,Crystal Violet Assay,Cytotoxicity Assay,flow cytometry Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs. Immunohistochemical staining Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs. Western Blot,Co-Immunoprecipitation,Cell Cycle Analysis,Crystal Violet Assay,Cytotoxicity Assay,flow cytometry XIAP Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs. 29771329 chr17 15227161 15229161 PMP22 In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression. human connective High+Lowthroughput Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer 否 Inherited peripheral neuropathies E_01_0471 CRISPR/Cas9,siRNA treatment,RT-qPCR,Spectral karyotyping In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression. Immunohistochemical staining In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression. CRISPR/Cas9,siRNA treatment,RT-qPCR,Spectral karyotyping PMP22,Pmp22 In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression.;In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression. 29769415 chr3 41191924 41193924 CTNNB1 Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. human Osteosarcoma High+Lowthroughput Up-regulation of microRNA-340 promotes osteosarcoma cell apoptosis while suppressing proliferation, migration, and invasion by inactivating the CTNNB1-mediated Notch signaling pathway 否 Osteosarcoma (OS) E_01_0472 Luciferase reporter assay,Western Blot,RT-QPCR,immunohistochemistry,in situ hybridization(ISH),transfection,MTT,flow cytometry,scratch test,transwell assay Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. Immunohistochemical staining Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. Luciferase reporter assay,Western Blot,RT-QPCR,immunohistochemistry,in situ hybridization(ISH),transfection,MTT,flow cytometry,scratch test,transwell assay Hes1,Runx2,Bax CTNNB1 Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS.;Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS.;Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. 29769310 chr17 57998205 58000205 SRSF1 Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis. human Epithelial High+Lowthroughput Tumor-associated intronic editing of HNRPLL generates a novel splicing variant linked to cell proliferation 否 tumour HeLa cell E_01_0473 gene knockdown,RT-PCR,qPCR,RNA-immunoprecipitation (RNA-IP) experiment,RNC-mRNA,Splicing luciferase reporter assay,RNA-seq,Gene expression analysis,Chromatin immunoprecipitation assay (ChIP) Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis. Immunohistochemical staining Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis. gene knockdown,RT-PCR,qPCR,RNA-immunoprecipitation (RNA-IP) experiment,RNC-mRNA,Splicing luciferase reporter assay,RNA-seq,Gene expression analysis,Chromatin immunoprecipitation assay (ChIP) SRSF1,ADAR,TGFBR1 CCND1 Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis.;Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis.;Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis. Gene expression profiling by RNA-seq revealed that E12A acts distinctly from HNRPLL and regulates a set of growth-related genes, such as cyclin CCND1 and growth factor receptor TGFBR1 Accordingly, silencing E12A expression leads to impaired clonogenic ability and enhanced sensitivity to doxorubicin, thus highlighting the significance of this alternative isoform in tumor cell survival. In summary, we present the interplay of RNA editing and splicing as a regulatory mechanism of gene expression and also its physiological relevance. These findings extend our understanding of transcriptional dynamics and provide a mechanistic explanation to the link of RNA editors to tumorigenesis. 29768655 chr7 148804347 148806347 EZH2 More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα. human connective High+Lowthroughput Let-7e inhibits TNF-α expression by targeting the methyl transferase EZH2 in DENV2-infected THP-1 cells 否 Other THP-1 cells E_01_0474 Western blot,Immunofluorescence assay,qRT-PCR,ELISA,Luciferase reporter assay,iTRAQ,miRNA or siRNA transfection,EZH2 knockdown,Smad3 knockdown More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα. Immunohistochemical staining More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα. Western blot,Immunofluorescence assay,qRT-PCR,ELISA,Luciferase reporter assay,iTRAQ,miRNA or siRNA transfection,EZH2 knockdown,Smad3 knockdown Smad3 EZH2 More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα. More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα. 29768212 chr1 186669486 186671486 PTGS2 mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA). human Synovial High+Lowthroughput mTOR Senses Environmental Cues to Shape the Fibroblast-like Synoviocyte Response to Inflammation 否 Inflammation, rheumatoid arthritis (RA) E_01_0475 Immunohistochemistry,Western Blot,qPCR,ELISA,EMSA,siRNA-Mediated Knockdown,Immunofluorescence Staining,Automated Imaging mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA). Immunohistochemical staining mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA). Immunohistochemistry,Western Blot,qPCR,ELISA,EMSA,siRNA-Mediated Knockdown,Immunofluorescence Staining,Automated Imaging CXCL11,TNFSF13B PTGS2,STAT1 mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA). mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA).;mTOR pathway activation is associated with decreased NF-κB-mediated gene expression (e.g., PTGS2, IL-6, and IL-8) but increased STAT1-dependent gene expression (e.g., CXCL11 and TNFSF13B). We further demonstrate how metabolic inputs, such as amino acids, impinge on TNF-mTORC1 signaling to differentially regulate pro-inflammatory signaling circuits. Our results define a critical role for mTOR in the regulation of the pro-inflammatory response in FLSs and unfold its pathogenic involvement in TNF-driven diseases, such as rheumatoid arthritis (RA). 29768199 chr14 21382478 21384478 CHD8 human adipose High+Lowthroughput The Autism-Related Protein CHD8 Cooperates with C/EBPβ to Regulate Adipogenesis 否 Autism spectrum disorder (ASD) preadipocyte E_01_0476 transgenic mice,RNA Interference,Luciferase Assay,RT-PCR,Real-Time PCR Analysis,Transfection,Immunoblot Analysis,Immunoprecipitation,ChIP,FAIRE,ChIP-Seq,RNA-Seq,Histopathology Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Immunohistochemical staining transgenic mice,RNA Interference,Luciferase Assay,RT-PCR,Real-Time PCR Analysis,Transfection,Immunoblot Analysis,Immunoprecipitation,ChIP,FAIRE,ChIP-Seq,RNA-Seq,Histopathology CHD8 29765957 chr16 67559780 67561780 CTCF The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer site of NFIB gene located downstream. NFIB is a transcription factor that promotes cell differentiation during development, has antiapoptotic effect, maintains stem cell populations in adult tissues, and also acts as epigenetic regulators. Our study found novel association of SNPs in the regulatory region in the 9p21-23 region with the frailty phenotype; signifying the importance of this locus in aging. human Epithelial High+Lowthroughput Genetic Insights Into Frailty: Association of 9p21-23 Locus With Frailty 是 rs1324192,rs7019262,rs518054,rs571221 Frailty, aging E_01_0477 WGS The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer site of NFIB gene located downstream. NFIB is a transcription factor that promotes cell differentiation during development, has antiapoptotic effect, maintains stem cell populations in adult tissues, and also acts as epigenetic regulators. Our study found novel association of SNPs in the regulatory region in the 9p21-23 region with the frailty phenotype; signifying the importance of this locus in aging. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer site of NFIB gene located downstream. NFIB is a transcription factor that promotes cell differentiation during development, has antiapoptotic effect, maintains stem cell populations in adult tissues, and also acts as epigenetic regulators. Our study found novel association of SNPs in the regulatory region in the 9p21-23 region with the frailty phenotype; signifying the importance of this locus in aging. Immunohistochemical staining The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer site of NFIB gene located downstream. NFIB is a transcription factor that promotes cell differentiation during development, has antiapoptotic effect, maintains stem cell populations in adult tissues, and also acts as epigenetic regulators. Our study found novel association of SNPs in the regulatory region in the 9p21-23 region with the frailty phenotype; signifying the importance of this locus in aging. WGS NFIB CTCF The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer site of NFIB gene located downstream. NFIB is a transcription factor that promotes cell differentiation during development, has antiapoptotic effect, maintains stem cell populations in adult tissues, and also acts as epigenetic regulators. Our study found novel association of SNPs in the regulatory region in the 9p21-23 region with the frailty phenotype; signifying the importance of this locus in aging. The prevalence of four SNPs (rs1324192, rs7019262, rs518054, and rs571221) risk alleles haplotype in this region was significantly higher (compared with other haplotypes) in frail older adults compared with non-frail older adults (29.7 vs. 20.8%, p = 0.0005, respectively). Functional analyses using in silico approaches placed rs518054 in the CTCF binding site as well as DNase hypersensitive region. Furthermore, rs518054 was found to be in an enhancer site of NFIB gene located downstream. NFIB is a transcription factor that promotes cell differentiation during development, has antiapoptotic effect, maintains stem cell populations in adult tissues, and also acts as epigenetic regulators. Our study found novel association of SNPs in the regulatory region in the 9p21-23 region with the frailty phenotype; signifying the importance of this locus in aging. 29763375 chr12 56268405 56270405 CS Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS. human Placental High+Lowthroughput Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity 否 Obesity E_01_0478 Real-time reverse transcription-polymerase chain reaction,protein immunoblotting,Enzyme-linked immunosorbent assay (ELISA),Chromosome conformation capture (3C) assay,Amplicon sequencing,bioinformatics, Chromatin immunoprecipitation (ChIP) assay Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS. Immunohistochemical staining Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS. Real-time reverse transcription-polymerase chain reaction,protein immunoblotting,Enzyme-linked immunosorbent assay (ELISA),Chromosome conformation capture (3C) assay,Amplicon sequencing,bioinformatics, Chromatin immunoprecipitation (ChIP) assay CS Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS. 29762844 chr9 117701608 117703608 TLR4 TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability. human connective High+Lowthroughput Free fatty acids mediates human umbilical vein endothelial cells inflammation through toll-like receptor-4 否 Inflammation in HUVECs HEK293 cell E_01_0479 Flow Cytometry,ELISA,qPCR,Western Blot,Cell Apoptosis Assay,Viability Assay TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability. Immunohistochemical staining TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability. Flow Cytometry,ELISA,qPCR,Western Blot,Cell Apoptosis Assay,Viability Assay TLR4,CCL5,CXCL10 TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability.;TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability.;TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability. 29761425 chr3 133743127 133745127 TF All the results suggested that genistein has the function of alleviating and treating LPS-induced DIC by anti-inflammatory and anticoagulation effects. We tentatively propose that genistein is a potential drug for auxiliary treatment of DIC. human lymphoid High+Lowthroughput Genistein has the function of alleviating and treating disseminated intravascular coagulation caused by lipopolysaccharide 否 Disseminated intravascular coagulation (DIC) RAW 264.7 E_01_0480 Western blot, H&E staining,PTAH staining,MTT All the results suggested that genistein has the function of alleviating and treating LPS-induced DIC by anti-inflammatory and anticoagulation effects. We tentatively propose that genistein is a potential drug for auxiliary treatment of DIC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq All the results suggested that genistein has the function of alleviating and treating LPS-induced DIC by anti-inflammatory and anticoagulation effects. We tentatively propose that genistein is a potential drug for auxiliary treatment of DIC. Immunohistochemical staining All the results suggested that genistein has the function of alleviating and treating LPS-induced DIC by anti-inflammatory and anticoagulation effects. We tentatively propose that genistein is a potential drug for auxiliary treatment of DIC. Western blot, H&E staining,PTAH staining,MTT TF All the results suggested that genistein has the function of alleviating and treating LPS-induced DIC by anti-inflammatory and anticoagulation effects. We tentatively propose that genistein is a potential drug for auxiliary treatment of DIC. 29761173 chr20 22578409 22580409 FOXA2 HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. human Liver High+Lowthroughput Liver-enriched transcription factor expression relates to chronic hepatic failure in humans 否 Liver metastasis, primary hepatocellular carcinoma, decompensated cirrhosis hepatocyte E_01_0481 qRT-PCR,immunohistochemistry HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. Immunohistochemical staining HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. qRT-PCR,immunohistochemistry OTC,CYP3A4,F7,LRP1 FOXA2 HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. ;HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. ;HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. ;HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. HNF4α and other members of the LETFs appear to be important regulators of hepatocyte function in patients with chronic hepatic failure. 29760797 chr11 8221840 8223840 LMO1 In summary, the current study confirmed that the potentially functional LMO1 rs2168101 G>T and rs3750952 G>C polymorphisms were associated with neuroblastoma susceptibility. This research requires further validation with larger sample sizes and inclusion of different ethnicities. human lymphoid High+Lowthroughput LMO1 super-enhancer polymorphism rs2168101 G>T correlates with decreased neuroblastoma risk in Chinese children 是 rs2168101,rs3750952 Neuroblastoma lymphocyte E_01_0482 RNA-seq In summary, the current study confirmed that the potentially functional LMO1 rs2168101 G>T and rs3750952 G>C polymorphisms were associated with neuroblastoma susceptibility. This research requires further validation with larger sample sizes and inclusion of different ethnicities. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In summary, the current study confirmed that the potentially functional LMO1 rs2168101 G>T and rs3750952 G>C polymorphisms were associated with neuroblastoma susceptibility. This research requires further validation with larger sample sizes and inclusion of different ethnicities. Immunohistochemical staining In summary, the current study confirmed that the potentially functional LMO1 rs2168101 G>T and rs3750952 G>C polymorphisms were associated with neuroblastoma susceptibility. This research requires further validation with larger sample sizes and inclusion of different ethnicities. RNA-seq LMO1,FAS In summary, the current study confirmed that the potentially functional LMO1 rs2168101 G>T and rs3750952 G>C polymorphisms were associated with neuroblastoma susceptibility. This research requires further validation with larger sample sizes and inclusion of different ethnicities.;In summary, the current study confirmed that the potentially functional LMO1 rs2168101 G>T and rs3750952 G>C polymorphisms were associated with neuroblastoma susceptibility. This research requires further validation with larger sample sizes and inclusion of different ethnicities. 29760402 chr15 39606417 39608417 Dcstamp Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation. mouse Nervous High+Lowthroughput Roles of Enhancer RNAs in RANKL-induced Osteoclast Differentiation Identified by Genome-wide Cap-analysis of Gene Expression using CRISPR/Cas9 否 Other E_01_0483 qRT-PCR,TRAP staining,CRISPR/Cas9,Retroviral gene transfer,shRNA transfection,CAGE, Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation. Immunohistochemical staining Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation. qRT-PCR,TRAP staining,CRISPR/Cas9,Retroviral gene transfer,shRNA transfection,CAGE, Dcstamp,Nfatc1,Nrp2 Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation.;Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation.;Furthermore, osteoclast differentiation was impaired by targeted deletion of bidirectional eRNA regions. The combined results show that eRNAs play important roles in osteoclastogenic gene regulation, and may therefore provide novel insights to elucidate the transcriptional mechanisms that control osteoclast differentiation. 29760161 chr16 67559664 67561664 CTCF Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies. human connective High+Lowthroughput CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia 否 Acute myeloid leukemia (AML) AML cell lines E_01_0484 RNA,qRT-PCR,RNA-seq,ChIP,ChIP-seq,ATAC-seq,4C-seq,CRISPR/Cas9, Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies. Immunohistochemical staining Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies. RNA,qRT-PCR,RNA-seq,ChIP,ChIP-seq,ATAC-seq,4C-seq,CRISPR/Cas9, CTCF,HOXA7,HOXA9,HOXA13 Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies.;Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies.;Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies.;Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies. 29759640 chr7 148804547 148806547 EZH2 The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. human Epithelial High+Lowthroughput Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma 否 Intrahepatic cholangiocarcinoma (ICC) cholangiocarcinoma RBE cell E_01_0485 Immunohistochemical staining and scoring,qRT-PCR,small interfering RNAs (siRNAs),qRT-PCR,Western blot,Bioinformatics analysis, The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. Immunohistochemical staining The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. Immunohistochemical staining and scoring,qRT-PCR,small interfering RNAs (siRNAs),qRT-PCR,Western blot,Bioinformatics analysis, VASH1 EZH2 The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. 29758293 chr9 81580468 81582468 TLE1 Using trio-based exome sequencing, we identified a homozygous missense mutation in the Transducin-like enhancer of split-1 (TLE1) gene, encoding for a non DNA-binding transcriptional corepressor, highly expressed in the postnatal brain. The regulation of the post-mitotic neural survival activity of TLE1 depends critically on an interaction with FOXG1, a gene shown to be involved in a postnatal microcephaly syndrome. Functional analysis on affected dermal fibroblasts showed a significant decrease in mitotic and proliferative index, indicating a lengthening of the cell cycle and a delay in mitosis, supporting that this gene could be a new candidate for postnatal microcephaly. human Nervous High+Lowthroughput TLE1, a key player in neurogenesis, a new candidate gene for autosomal recessive postnatal microcephaly 是 rs201140985 Postnatal microcephaly neural progenitor cell E_01_0486 Immunostaining Using trio-based exome sequencing, we identified a homozygous missense mutation in the Transducin-like enhancer of split-1 (TLE1) gene, encoding for a non DNA-binding transcriptional corepressor, highly expressed in the postnatal brain. The regulation of the post-mitotic neural survival activity of TLE1 depends critically on an interaction with FOXG1, a gene shown to be involved in a postnatal microcephaly syndrome. Functional analysis on affected dermal fibroblasts showed a significant decrease in mitotic and proliferative index, indicating a lengthening of the cell cycle and a delay in mitosis, supporting that this gene could be a new candidate for postnatal microcephaly. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using trio-based exome sequencing, we identified a homozygous missense mutation in the Transducin-like enhancer of split-1 (TLE1) gene, encoding for a non DNA-binding transcriptional corepressor, highly expressed in the postnatal brain. The regulation of the post-mitotic neural survival activity of TLE1 depends critically on an interaction with FOXG1, a gene shown to be involved in a postnatal microcephaly syndrome. Functional analysis on affected dermal fibroblasts showed a significant decrease in mitotic and proliferative index, indicating a lengthening of the cell cycle and a delay in mitosis, supporting that this gene could be a new candidate for postnatal microcephaly. Immunohistochemical staining Using trio-based exome sequencing, we identified a homozygous missense mutation in the Transducin-like enhancer of split-1 (TLE1) gene, encoding for a non DNA-binding transcriptional corepressor, highly expressed in the postnatal brain. The regulation of the post-mitotic neural survival activity of TLE1 depends critically on an interaction with FOXG1, a gene shown to be involved in a postnatal microcephaly syndrome. Functional analysis on affected dermal fibroblasts showed a significant decrease in mitotic and proliferative index, indicating a lengthening of the cell cycle and a delay in mitosis, supporting that this gene could be a new candidate for postnatal microcephaly. Immunostaining FOXG1 TLE1 Using trio-based exome sequencing, we identified a homozygous missense mutation in the Transducin-like enhancer of split-1 (TLE1) gene, encoding for a non DNA-binding transcriptional corepressor, highly expressed in the postnatal brain. The regulation of the post-mitotic neural survival activity of TLE1 depends critically on an interaction with FOXG1, a gene shown to be involved in a postnatal microcephaly syndrome. Functional analysis on affected dermal fibroblasts showed a significant decrease in mitotic and proliferative index, indicating a lengthening of the cell cycle and a delay in mitosis, supporting that this gene could be a new candidate for postnatal microcephaly. Using trio-based exome sequencing, we identified a homozygous missense mutation in the Transducin-like enhancer of split-1 (TLE1) gene, encoding for a non DNA-binding transcriptional corepressor, highly expressed in the postnatal brain. The regulation of the post-mitotic neural survival activity of TLE1 depends critically on an interaction with FOXG1, a gene shown to be involved in a postnatal microcephaly syndrome. Functional analysis on affected dermal fibroblasts showed a significant decrease in mitotic and proliferative index, indicating a lengthening of the cell cycle and a delay in mitosis, supporting that this gene could be a new candidate for postnatal microcephaly. 29755131 chr7 152132016 152134016 KMT2C From a therapeutic standpoint, KMT2C-depleted cells that develop hormone-independence retain their dependence on ERα, displaying ongoing sensitivity to ERα antagonists. We conclude that KMT2C is a key regulator of ERα activity whose loss uncouples breast cancer proliferation from hormone abundance. human Epithelial High+Lowthroughput KMT2C mediates the estrogen dependence of breast cancer through regulation of ERα enhancer function 否 mammary cancer SKBR3 cell E_01_0487 CRISPR/Cas9,next-generation sequencing (IMPACT) assay,Proliferation assays,Immunoblotting,Lentiviral Infections,Quantitative RT-PCR,Chromatin Immunoprecipitation,Immunohistochemistry,Rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME),Chromatin Immunoprecipitation followed by sequencing, From a therapeutic standpoint, KMT2C-depleted cells that develop hormone-independence retain their dependence on ERα, displaying ongoing sensitivity to ERα antagonists. We conclude that KMT2C is a key regulator of ERα activity whose loss uncouples breast cancer proliferation from hormone abundance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq From a therapeutic standpoint, KMT2C-depleted cells that develop hormone-independence retain their dependence on ERα, displaying ongoing sensitivity to ERα antagonists. We conclude that KMT2C is a key regulator of ERα activity whose loss uncouples breast cancer proliferation from hormone abundance. Immunohistochemical staining From a therapeutic standpoint, KMT2C-depleted cells that develop hormone-independence retain their dependence on ERα, displaying ongoing sensitivity to ERα antagonists. We conclude that KMT2C is a key regulator of ERα activity whose loss uncouples breast cancer proliferation from hormone abundance. CRISPR/Cas9,next-generation sequencing (IMPACT) assay,Proliferation assays,Immunoblotting,Lentiviral Infections,Quantitative RT-PCR,Chromatin Immunoprecipitation,Immunohistochemistry,Rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME),Chromatin Immunoprecipitation followed by sequencing, KMT2C,FOXA1 From a therapeutic standpoint, KMT2C-depleted cells that develop hormone-independence retain their dependence on ERα, displaying ongoing sensitivity to ERα antagonists. We conclude that KMT2C is a key regulator of ERα activity whose loss uncouples breast cancer proliferation from hormone abundance.;From a therapeutic standpoint, KMT2C-depleted cells that develop hormone-independence retain their dependence on ERα, displaying ongoing sensitivity to ERα antagonists. We conclude that KMT2C is a key regulator of ERα activity whose loss uncouples breast cancer proliferation from hormone abundance. 29755129 chr13 27063070 27065070 USP12 Consequently, USP12 levels are predictive not only of cancer development but also of patient's therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer. human connective High+Lowthroughput Molecular mechanism of the TP53-MDM2-AR-AKT signalling network regulation by USP12 否 prostatic cancer LNCaP E_01_0488 transfection,siRNA gene silencing,Immunoprecipitation (IP),Immunohistochemistry,Colony formation,Chromatin immunoprecipitation (ChIP),qPCR, Consequently, USP12 levels are predictive not only of cancer development but also of patient's therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Consequently, USP12 levels are predictive not only of cancer development but also of patient's therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer. Immunohistochemical staining Consequently, USP12 levels are predictive not only of cancer development but also of patient's therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer. transfection,siRNA gene silencing,Immunoprecipitation (IP),Immunohistochemistry,Colony formation,Chromatin immunoprecipitation (ChIP),qPCR, USP12 TP53 Consequently, USP12 levels are predictive not only of cancer development but also of patient's therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer. Consequently, USP12 levels are predictive not only of cancer development but also of patient's therapy resistance, relapse and survival. Therefore, our findings suggest that USP12 could serve as a promising therapeutic target in currently incurable castrate-resistant prostate cancer. 29754817 chr12 47838311 47840311 VDR Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D. human connective High+Lowthroughput Vitamin D Switches BAF Complexes to Protect β Cells 否 Type 2 diabetes (T2D) INS1 cell E_01_0489 CRISPR screening,RNA-Seq,qPCR,H&E staining,Immunohistochemistry,immunofluorescence,Immunoprecipitation,siRNA knockdown,transfection,shRNA knockdown,FACS analysis,ELISA,Chromatin Immunoprecipitation,ChIP-Seq,ATAC-Seq,Transmission electronic microscopy,LC-MS Analysis, Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D. Immunohistochemical staining Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D. CRISPR screening,RNA-Seq,qPCR,H&E staining,Immunohistochemistry,immunofluorescence,Immunoprecipitation,siRNA knockdown,transfection,shRNA knockdown,FACS analysis,ELISA,Chromatin Immunoprecipitation,ChIP-Seq,ATAC-Seq,Transmission electronic microscopy,LC-MS Analysis, BRD7,BRD9 CYP27B1 Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D.;Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D. Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D. 29754779 chr9 134132377 134134377 WDR5 In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo. human Epithelial High+Lowthroughput A Linc1405/Eomes Complex Promotes Cardiac Mesoderm Specification and Cardiogenesis 否 Other embryonic stem cell E_01_0490 PCR,CRISPR,Fluorescence activated cell sorter analysis,Microarray analysis,Chromatin immunoprecipitation,Fluorescent in situ hybridization,Quantitative RT-PCR,Western blot,Immunostaining,RIP assay,RNA immunoprecipitation,Luciferase reporter assay,Co-immunoprecipitation,Echocardiography analysis,Hematoxylin and Eeosin staining, In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo. Immunohistochemical staining In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo. PCR,CRISPR,Fluorescence activated cell sorter analysis,Microarray analysis,Chromatin immunoprecipitation,Fluorescent in situ hybridization,Quantitative RT-PCR,Western blot,Immunostaining,RIP assay,RNA immunoprecipitation,Luciferase reporter assay,Co-immunoprecipitation,Echocardiography analysis,Hematoxylin and Eeosin staining, WDR5,Mesp1,Eomes In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo.;In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo.;In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo. 29754769 chr2 45385835 45387835 SRBD1 It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of _x0001_300 autism-affected family trios across five studies and discovered several autism risk genes.The software is freely available for all research uses. human / High+Lowthroughput A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies 否 autism E_01_0491 WES,WGS,TADA-Annotations(TADA-A), It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of _x0001_300 autism-affected family trios across five studies and discovered several autism risk genes.The software is freely available for all research uses. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of _x0001_300 autism-affected family trios across five studies and discovered several autism risk genes.The software is freely available for all research uses. Immunohistochemical staining It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of _x0001_300 autism-affected family trios across five studies and discovered several autism risk genes.The software is freely available for all research uses. WES,WGS,TADA-Annotations(TADA-A), SRBD1 It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of _x0001_300 autism-affected family trios across five studies and discovered several autism risk genes.The software is freely available for all research uses. 29751043 chr7 45108269 45110269 Bax In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. mouse connective High+Lowthroughput Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro 否 Other HEI-OC1 cell E_01_0492 Quantitative real-time PCR,ELISA,Western blot,Cochlear hair cell staining, In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Immunohistochemical staining In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Quantitative real-time PCR,ELISA,Western blot,Cochlear hair cell staining, Bax,Bcl2 In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness.;In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. 29750193 chr3 10290270 10292270 SEC13 mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration. human connective High+Lowthroughput Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration 否 Other H1299 cell E_01_0493 siRNA,transfection,Immunoprecipitation analysis,mmunoblotting,immunofluorescence, mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration. Immunohistochemical staining mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration. siRNA,transfection,Immunoprecipitation analysis,mmunoblotting,immunofluorescence, SEC13 mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration. 29749927 chr9 63857441 63859441 Smad6 Functional experiments prototypically validated the strongly epigenetically regulated inhibitors of TGFβ family signaling SMAD6 and SMAD7 as regulators of EC quiescence. These data establish the transcriptional and epigenetic landscape of vascular quiescence that will serve as a foundation for further mechanistic studies of vascular homeostasis and disease-associated activation. mouse Lung High+Lowthroughput The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium 否 Other HUVECs cell E_01_0494 FACS,Immunofluorescence staining,Elisa,Immunoblot,qPCR,RNA-seq,T-WGBS,MassARRAY,Interactome analysis, Functional experiments prototypically validated the strongly epigenetically regulated inhibitors of TGFβ family signaling SMAD6 and SMAD7 as regulators of EC quiescence. These data establish the transcriptional and epigenetic landscape of vascular quiescence that will serve as a foundation for further mechanistic studies of vascular homeostasis and disease-associated activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional experiments prototypically validated the strongly epigenetically regulated inhibitors of TGFβ family signaling SMAD6 and SMAD7 as regulators of EC quiescence. These data establish the transcriptional and epigenetic landscape of vascular quiescence that will serve as a foundation for further mechanistic studies of vascular homeostasis and disease-associated activation. Immunohistochemical staining Functional experiments prototypically validated the strongly epigenetically regulated inhibitors of TGFβ family signaling SMAD6 and SMAD7 as regulators of EC quiescence. These data establish the transcriptional and epigenetic landscape of vascular quiescence that will serve as a foundation for further mechanistic studies of vascular homeostasis and disease-associated activation. FACS,Immunofluorescence staining,Elisa,Immunoblot,qPCR,RNA-seq,T-WGBS,MassARRAY,Interactome analysis, Smad6,Smad7 Functional experiments prototypically validated the strongly epigenetically regulated inhibitors of TGFβ family signaling SMAD6 and SMAD7 as regulators of EC quiescence. These data establish the transcriptional and epigenetic landscape of vascular quiescence that will serve as a foundation for further mechanistic studies of vascular homeostasis and disease-associated activation.;Functional experiments prototypically validated the strongly epigenetically regulated inhibitors of TGFβ family signaling SMAD6 and SMAD7 as regulators of EC quiescence. These data establish the transcriptional and epigenetic landscape of vascular quiescence that will serve as a foundation for further mechanistic studies of vascular homeostasis and disease-associated activation. 29749529 chr17 44900352 44902352 GFAP In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future. human connective High+Lowthroughput α?synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum?Golgi compartment 否 Parkinson's disease (PD) 293FT E_01_0495 Immunofluorescence,Immunoassay,Western blot, CHOP Knockdown,transfection,Immunostaining,flow cytometry,RNA-seq,siRNA, In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future. Immunohistochemical staining In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future. Immunofluorescence,Immunoassay,Western blot, CHOP Knockdown,transfection,Immunostaining,flow cytometry,RNA-seq,siRNA, MAP2 GFAP,GDNF In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future. In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future.;In addition, Golgi fragmentation was observed in the process. On the other hand, it was also demonstrated, in a primary neuronal‑astroglial co‑culture system, that the overexpression of α‑syn significantly decreased the levels of glia‑derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER‑Golgi compartment in astrocytes overexpressing α‑syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth. Taken together, the results of the present study offer further insights into the pathogenesis of PD from the perspective of astrocytes, which may provide novel strategies for the diagnosis and treatment of PD in the future. 29749465 chrY 2784042 2786042 SRY In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction. human Mammary High+Lowthroughput 12(S)-HETE induces lymph endothelial cell retraction in?vitro by upregulation of SOX18 否 mammary cancer MDA-MB231 breast cancer cell E_01_0496 CCID assay,Transfection,RT-qPCR,Western blot,immunofluorescence, In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction. Immunohistochemical staining In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction. CCID assay,Transfection,RT-qPCR,Western blot,immunofluorescence, PROX1 SRY,SOX18 In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction. In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction.;In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction. 29749460 chr6 7878754 7880754 TXNDC5 These findings suggested that TXNDC5 functions as an important stress survival factor to maintain tumorigenesis of CRC cells under hypoxia by regulating hypoxia‑induced ROS/ER stress signaling. The present study provided novel insights into the role of TXNDC5 in the tumorigenesis of CRC. human Colon High+Lowthroughput Role of TXNDC5 in tumorigenesis of colorectal cancer cells: In vivo and in vitro evidence 否 Colorectal cancer (CRC) rKo cell E_01_0497 Western blot,RT‑qPCR,Immunohistochemistry,MTT cell proliferation assay,Colony formation assay,Cell apoptosis assay,Transient transfection of small interfering (si)RNA, These findings suggested that TXNDC5 functions as an important stress survival factor to maintain tumorigenesis of CRC cells under hypoxia by regulating hypoxia‑induced ROS/ER stress signaling. The present study provided novel insights into the role of TXNDC5 in the tumorigenesis of CRC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings suggested that TXNDC5 functions as an important stress survival factor to maintain tumorigenesis of CRC cells under hypoxia by regulating hypoxia‑induced ROS/ER stress signaling. The present study provided novel insights into the role of TXNDC5 in the tumorigenesis of CRC. Immunohistochemical staining These findings suggested that TXNDC5 functions as an important stress survival factor to maintain tumorigenesis of CRC cells under hypoxia by regulating hypoxia‑induced ROS/ER stress signaling. The present study provided novel insights into the role of TXNDC5 in the tumorigenesis of CRC. Western blot,RT‑qPCR,Immunohistochemistry,MTT cell proliferation assay,Colony formation assay,Cell apoptosis assay,Transient transfection of small interfering (si)RNA, TXNDC5 ATF4 These findings suggested that TXNDC5 functions as an important stress survival factor to maintain tumorigenesis of CRC cells under hypoxia by regulating hypoxia‑induced ROS/ER stress signaling. The present study provided novel insights into the role of TXNDC5 in the tumorigenesis of CRC. These findings suggested that TXNDC5 functions as an important stress survival factor to maintain tumorigenesis of CRC cells under hypoxia by regulating hypoxia‑induced ROS/ER stress signaling. The present study provided novel insights into the role of TXNDC5 in the tumorigenesis of CRC. 29749452 chr2 192746411 192748411 PCGEM1 In conclusion, the present study demonstrated a positive regulatory association between MEF2 and PCGEM1, and a reciprocal negative regulatory association between PCGEM1 and miR‑148a that controls cell apoptosis. The present study, therefore, provides new insights into the mechanism of PCGEM1 function in prostate cancer development. human Prostate cancer High+Lowthroughput MEF2?activated long non?coding RNA PCGEM1 promotes cell proliferation in hormone?refractory prostate cancer through downregulation of miR?148a 否 prostatic cancer LNCaP E_01_0498 RT‑qPCR,Western blot,Cell transfection,luciferase reporter assay,Chromatin immunoprecipitation (ChIP) assay,Apoptosis assay,flow cytometry,siRNA, In conclusion, the present study demonstrated a positive regulatory association between MEF2 and PCGEM1, and a reciprocal negative regulatory association between PCGEM1 and miR‑148a that controls cell apoptosis. The present study, therefore, provides new insights into the mechanism of PCGEM1 function in prostate cancer development. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, the present study demonstrated a positive regulatory association between MEF2 and PCGEM1, and a reciprocal negative regulatory association between PCGEM1 and miR‑148a that controls cell apoptosis. The present study, therefore, provides new insights into the mechanism of PCGEM1 function in prostate cancer development. Immunohistochemical staining In conclusion, the present study demonstrated a positive regulatory association between MEF2 and PCGEM1, and a reciprocal negative regulatory association between PCGEM1 and miR‑148a that controls cell apoptosis. The present study, therefore, provides new insights into the mechanism of PCGEM1 function in prostate cancer development. RT‑qPCR,Western blot,Cell transfection,luciferase reporter assay,Chromatin immunoprecipitation (ChIP) assay,Apoptosis assay,flow cytometry,siRNA, PCGEM1 In conclusion, the present study demonstrated a positive regulatory association between MEF2 and PCGEM1, and a reciprocal negative regulatory association between PCGEM1 and miR‑148a that controls cell apoptosis. The present study, therefore, provides new insights into the mechanism of PCGEM1 function in prostate cancer development. 29748386 chr5 132437549 132439549 IRF1 In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues. human Adrenal High+Lowthroughput Frequent interferon regulatory factor 1 (IRF1) binding at remote elements without histone modification 否 Other SW13 cell E_01_0499 ChIP–qPCR,qPCR,ChIP,ChIP-chip assays, In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues. Immunohistochemical staining In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues. ChIP–qPCR,qPCR,ChIP,ChIP-chip assays, IRF1,STAT1,SMARCA4 In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues.;In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues.;In conclusion, although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues. 29748098 chr7 148804691 148806691 EZH2 Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated. human Epithelial High+Lowthroughput Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma 否 Upper urothelial carcinoma (utuc) epithelial cell E_01_0500 immunohistochemical staining (IHC), Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated. Immunohistochemical staining Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated. immunohistochemical staining (IHC), EZH2 Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated. 29743187 chr12 100470925 100472925 NR1H4 In summary, NAFLD was characterized by an imbalance in arachidonate metabolism. FXR activation reprogramed arachidonate metabolism by inducing P450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition required active P450 epoxygenases. human Liver High+Lowthroughput Effects of Farnesoid X Receptor Activation on Arachidonic Acid Metabolism, NF-kB Signaling, and Hepatic Inflammation 否 Non alcoholic fatty liver disease (NAFLD), inflammation THP-1 cells E_01_0501 Migration assay,Transient transfection,gene expression analysis,immunostaining, In summary, NAFLD was characterized by an imbalance in arachidonate metabolism. FXR activation reprogramed arachidonate metabolism by inducing P450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition required active P450 epoxygenases. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In summary, NAFLD was characterized by an imbalance in arachidonate metabolism. FXR activation reprogramed arachidonate metabolism by inducing P450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition required active P450 epoxygenases. Immunohistochemical staining In summary, NAFLD was characterized by an imbalance in arachidonate metabolism. FXR activation reprogramed arachidonate metabolism by inducing P450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition required active P450 epoxygenases. Migration assay,Transient transfection,gene expression analysis,immunostaining, LTB NR1H4 In summary, NAFLD was characterized by an imbalance in arachidonate metabolism. FXR activation reprogramed arachidonate metabolism by inducing P450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition required active P450 epoxygenases. In summary, NAFLD was characterized by an imbalance in arachidonate metabolism. FXR activation reprogramed arachidonate metabolism by inducing P450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition required active P450 epoxygenases. 29742982 chr9 21137636 21139636 Keap1 Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide. mouse Epithelial High+Lowthroughput NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland 否 Other PCCL3 cell E_01_0502 real-time PCR,Protein isolation,Western immunoblotting,immunohistochemistry,analysis of protein oxidation,RNA interference,Chromatin immunoprecip,Cell transfections,reporter assay,CRISPR/Cas9, Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide. Immunohistochemical staining Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide. real-time PCR,Protein isolation,Western immunoblotting,immunohistochemistry,analysis of protein oxidation,RNA interference,Chromatin immunoprecip,Cell transfections,reporter assay,CRISPR/Cas9, Keap1,Tg NFE2 Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.;Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide. Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide. 29740349 chr22 28791734 28793734 XBP1 The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. human Epithelial High+Lowthroughput Severe Burn-Induced Intestinal Epithelial Barrier Dysfunction Is Associated With Endoplasmic Reticulum Stress and Autophagy in Mice 否 Intestinal barrier dysfunction epithelial cell E_01_0503 histological,immunofluorescent,Western blot,Immunofluorescent Staining,Microscopy,Image Analysis, The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. Immunohistochemical staining The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. histological,immunofluorescent,Western blot,Immunofluorescent Staining,Microscopy,Image Analysis, ATG5 XBP1 The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. 29740122 chr1 150643764 150645764 GOLPH3L Furthermore, we identify genetic variants affecting expression of 927 enhancers, which we refer to as enhancer expression quantitative loci or eeQTLs. Enhancer expression patterns are consistent across studies, including differentially expressed eRNAs and eeQTLs. Combining eeQTLs with a genome-wide association study of schizophrenia identifies a genetic variant that alters enhancer function and expression of its target gene, GOLPH3L. Our novel approach to analyzing enhancer transcription is adaptable to other large-scale, non-poly-A depleted, RNA-seq studies. human Nervous High+Lowthroughput Differential activity of transcribed enhancers in the prefrontal cortex of 537 cases with schizophrenia and controls 否 Schizophrenia neuronal cell E_01_0504 RNA-seq,Gene co-expression analyses,ATACseq, Furthermore, we identify genetic variants affecting expression of 927 enhancers, which we refer to as enhancer expression quantitative loci or eeQTLs. Enhancer expression patterns are consistent across studies, including differentially expressed eRNAs and eeQTLs. Combining eeQTLs with a genome-wide association study of schizophrenia identifies a genetic variant that alters enhancer function and expression of its target gene, GOLPH3L. Our novel approach to analyzing enhancer transcription is adaptable to other large-scale, non-poly-A depleted, RNA-seq studies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, we identify genetic variants affecting expression of 927 enhancers, which we refer to as enhancer expression quantitative loci or eeQTLs. Enhancer expression patterns are consistent across studies, including differentially expressed eRNAs and eeQTLs. Combining eeQTLs with a genome-wide association study of schizophrenia identifies a genetic variant that alters enhancer function and expression of its target gene, GOLPH3L. Our novel approach to analyzing enhancer transcription is adaptable to other large-scale, non-poly-A depleted, RNA-seq studies. Immunohistochemical staining Furthermore, we identify genetic variants affecting expression of 927 enhancers, which we refer to as enhancer expression quantitative loci or eeQTLs. Enhancer expression patterns are consistent across studies, including differentially expressed eRNAs and eeQTLs. Combining eeQTLs with a genome-wide association study of schizophrenia identifies a genetic variant that alters enhancer function and expression of its target gene, GOLPH3L. Our novel approach to analyzing enhancer transcription is adaptable to other large-scale, non-poly-A depleted, RNA-seq studies. RNA-seq,Gene co-expression analyses,ATACseq, GOLPH3L Furthermore, we identify genetic variants affecting expression of 927 enhancers, which we refer to as enhancer expression quantitative loci or eeQTLs. Enhancer expression patterns are consistent across studies, including differentially expressed eRNAs and eeQTLs. Combining eeQTLs with a genome-wide association study of schizophrenia identifies a genetic variant that alters enhancer function and expression of its target gene, GOLPH3L. Our novel approach to analyzing enhancer transcription is adaptable to other large-scale, non-poly-A depleted, RNA-seq studies. 29739060 chr1 206764791 206766791 IL10 Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding. human Nervous High+Lowthroughput Lower Expression of miR-10a in Coronary Artery Disease and its Association with Pro/Anti-Inflammatory Cytokines 否 Coronary artery disease (CAD), atherosclerosis peripheral blood mononuclear cell E_01_0505 Quantitative real-time PCR,ELISA, Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding. Immunohistochemical staining Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding. Quantitative real-time PCR,ELISA, IL10 Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding. 29738565 chr4 71739247 71741247 GC Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. Furthermore blocked GBR are in a closed conformation prior to Hic-5 depletion, and require Hic-5 depletion and glucocorticoid treatment to create an open conformation necessary for GR occupancy. A transcription factor binding motif characteristic of the ETS family was enriched near blocked GBR and blocked genes but not near non-blocked GBR or non-blocked GR target genes. Thus, we identify specific differences in chromatin conformation, chromatin remodeler requirements, and local DNA sequence motifs that contribute to gene-specific actions of transcription factors and coregulators. These findings shed light on mechanisms that contribute to binding site selection by transcription factors, which vary in a cell type-specific manner. human Osteosarcoma High+Lowthroughput Different chromatin and DNA sequence characteristics define glucocorticoid receptor binding sites that are blocked or not blocked by coregulator Hic-5 否 Other U2OS osteosarcoma cells E_01_0506 siRNA transfection,ChIP,Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. Furthermore blocked GBR are in a closed conformation prior to Hic-5 depletion, and require Hic-5 depletion and glucocorticoid treatment to create an open conformation necessary for GR occupancy. A transcription factor binding motif characteristic of the ETS family was enriched near blocked GBR and blocked genes but not near non-blocked GBR or non-blocked GR target genes. Thus, we identify specific differences in chromatin conformation, chromatin remodeler requirements, and local DNA sequence motifs that contribute to gene-specific actions of transcription factors and coregulators. These findings shed light on mechanisms that contribute to binding site selection by transcription factors, which vary in a cell type-specific manner. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. Furthermore blocked GBR are in a closed conformation prior to Hic-5 depletion, and require Hic-5 depletion and glucocorticoid treatment to create an open conformation necessary for GR occupancy. A transcription factor binding motif characteristic of the ETS family was enriched near blocked GBR and blocked genes but not near non-blocked GBR or non-blocked GR target genes. Thus, we identify specific differences in chromatin conformation, chromatin remodeler requirements, and local DNA sequence motifs that contribute to gene-specific actions of transcription factors and coregulators. These findings shed light on mechanisms that contribute to binding site selection by transcription factors, which vary in a cell type-specific manner. Immunohistochemical staining Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. Furthermore blocked GBR are in a closed conformation prior to Hic-5 depletion, and require Hic-5 depletion and glucocorticoid treatment to create an open conformation necessary for GR occupancy. A transcription factor binding motif characteristic of the ETS family was enriched near blocked GBR and blocked genes but not near non-blocked GBR or non-blocked GR target genes. Thus, we identify specific differences in chromatin conformation, chromatin remodeler requirements, and local DNA sequence motifs that contribute to gene-specific actions of transcription factors and coregulators. These findings shed light on mechanisms that contribute to binding site selection by transcription factors, which vary in a cell type-specific manner. siRNA transfection,ChIP,Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), GC,CHD9 Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. Furthermore blocked GBR are in a closed conformation prior to Hic-5 depletion, and require Hic-5 depletion and glucocorticoid treatment to create an open conformation necessary for GR occupancy. A transcription factor binding motif characteristic of the ETS family was enriched near blocked GBR and blocked genes but not near non-blocked GBR or non-blocked GR target genes. Thus, we identify specific differences in chromatin conformation, chromatin remodeler requirements, and local DNA sequence motifs that contribute to gene-specific actions of transcription factors and coregulators. These findings shed light on mechanisms that contribute to binding site selection by transcription factors, which vary in a cell type-specific manner.;Here we show genome-wide that blocked GBR generally require CHD9 and BRM for GR occupancy in contrast to GBR that are not blocked by Hic-5. Hic-5 blocked GBR are enriched near Hic-5 blocked GR target genes but not near GR target genes that are not blocked by Hic-5. Furthermore blocked GBR are in a closed conformation prior to Hic-5 depletion, and require Hic-5 depletion and glucocorticoid treatment to create an open conformation necessary for GR occupancy. A transcription factor binding motif characteristic of the ETS family was enriched near blocked GBR and blocked genes but not near non-blocked GBR or non-blocked GR target genes. Thus, we identify specific differences in chromatin conformation, chromatin remodeler requirements, and local DNA sequence motifs that contribute to gene-specific actions of transcription factors and coregulators. These findings shed light on mechanisms that contribute to binding site selection by transcription factors, which vary in a cell type-specific manner. 29738494 chr19 41216765 41218765 AXL Using the first X-ray structure of the hYAP50⁻71-hTEAD1209⁻426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD. Four different chemical families have been identified and evaluated using biophysical techniques (thermal shift assay, microscale thermophoresis) and in cellulo assays (luciferase activity in transfected HEK293 cells, RTqPCR in MDA-MB231 cells). A first promising hit with micromolar inhibition in the luciferase gene reporter assay was discovered. This hit also decreased mRNA levels of TEAD target genes. human connective High+Lowthroughput Toward the Discovery of a Novel Class of YAP?TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP?TEAD Protein?Protein Interface 否 cancer HEK293 cell E_01_0507 RT-qPCR,luciferase gene reporter assay,Microscale Thermophoresis, Using the first X-ray structure of the hYAP50⁻71-hTEAD1209⁻426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD. Four different chemical families have been identified and evaluated using biophysical techniques (thermal shift assay, microscale thermophoresis) and in cellulo assays (luciferase activity in transfected HEK293 cells, RTqPCR in MDA-MB231 cells). A first promising hit with micromolar inhibition in the luciferase gene reporter assay was discovered. This hit also decreased mRNA levels of TEAD target genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using the first X-ray structure of the hYAP50⁻71-hTEAD1209⁻426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD. Four different chemical families have been identified and evaluated using biophysical techniques (thermal shift assay, microscale thermophoresis) and in cellulo assays (luciferase activity in transfected HEK293 cells, RTqPCR in MDA-MB231 cells). A first promising hit with micromolar inhibition in the luciferase gene reporter assay was discovered. This hit also decreased mRNA levels of TEAD target genes. Immunohistochemical staining Using the first X-ray structure of the hYAP50⁻71-hTEAD1209⁻426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD. Four different chemical families have been identified and evaluated using biophysical techniques (thermal shift assay, microscale thermophoresis) and in cellulo assays (luciferase activity in transfected HEK293 cells, RTqPCR in MDA-MB231 cells). A first promising hit with micromolar inhibition in the luciferase gene reporter assay was discovered. This hit also decreased mRNA levels of TEAD target genes. RT-qPCR,luciferase gene reporter assay,Microscale Thermophoresis, AXL Using the first X-ray structure of the hYAP50⁻71-hTEAD1209⁻426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD. Four different chemical families have been identified and evaluated using biophysical techniques (thermal shift assay, microscale thermophoresis) and in cellulo assays (luciferase activity in transfected HEK293 cells, RTqPCR in MDA-MB231 cells). A first promising hit with micromolar inhibition in the luciferase gene reporter assay was discovered. This hit also decreased mRNA levels of TEAD target genes. 29737550 chr7 45108306 45110306 Bax In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings. mouse Placental High+Lowthroughput The association of the placental CASPASE-3 gene polymorphisms and preeclampsia susceptibility and in-silico analysis 是 rs4647602,rs4647610 Preeclampsia E_01_0508 PCR-RFLP,Bioinformatics analysis, In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings. Immunohistochemical staining In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings. PCR-RFLP,Bioinformatics analysis, Bax In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings. 29736797 chr3 41192441 41194441 CTNNB1 We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC. human / High+Lowthroughput β-catenin (CTNNB1) mutation and LEF1 expression in sinonasal glomangiopericytoma (sinonasal-type hemangiopericytoma) 否 Sinonasal tubular cell tumor (sn-gpc) E_01_0509 Immunohistochemistry,PCR,Sanger sequencing, We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC. Immunohistochemical staining We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC. Immunohistochemistry,PCR,Sanger sequencing, CTNNB1,LEF1 We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC.;We examined three SN-GPCs by immunohistochemistry and CTNNB1 mutation analysis. All cases expressed nuclear β-catenin. We identified CTNNB1 exon 3 mutations in two analyzable cases. Lymphoid enhancer-binding factor 1 (LEF1), a protein downstream from β-catenin, was also expressed in all cases. Our results further characterized the activation of the Wnt signaling pathway caused by CTNNB1 exon 3 mutation and suggest the utility of LEF1 immunohistochemistry in the differential diagnosis of SN-GPC. 29736028 chr1 205825403 205827403 PM20D1 We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD. human lymphoid High+Lowthroughput PM20D1 is a?quantitative trait locus associated with Alzheimer's disease 是 rs708727 Alzheimer's disease (AD) Immortalized B cells E_01_0510 GWAS,EWAS,RT–PCR,quantitative real-time PCR,DNA methylation,RNA expression,Chromatin conformation capture (3C) protocol,Chromatin immunoprecipitation (ChIP) assays,Cloning,Immunohistochemistry (IHC),Western blot,Luciferase assays,Cell viability assays,Lentivirus production,Amyloid plaques,Amyloid-β assays, We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD. Immunohistochemical staining We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD. GWAS,EWAS,RT–PCR,quantitative real-time PCR,DNA methylation,RNA expression,Chromatin conformation capture (3C) protocol,Chromatin immunoprecipitation (ChIP) assays,Cloning,Immunohistochemistry (IHC),Western blot,Luciferase assays,Cell viability assays,Lentivirus production,Amyloid plaques,Amyloid-β assays, PM20D1 We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD. 29736013 chrX 44870832 44872832 KDM6A Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs. human connective High+Lowthroughput UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs 否 Acute myeloid leukemia E_01_0511 PCR,qRT–PCR,cDNA synthesis,Flow cytometry,Protein extraction,immunoblotting,coimmunoprecipitation,Proliferation assays,Plasmids,cloning,Histological analysis of mouse tissue,RNA extraction,RNA-seq,ChIP–seq,ChIP–qPCR,ATAC–seq,Chip–seq,motif analysis,GSEA,data visualization,LC–MS/MS analysis,Exome sequencing,Exome data analysis, Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs. Immunohistochemical staining Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs. PCR,qRT–PCR,cDNA synthesis,Flow cytometry,Protein extraction,immunoblotting,coimmunoprecipitation,Proliferation assays,Plasmids,cloning,Histological analysis of mouse tissue,RNA extraction,RNA-seq,ChIP–seq,ChIP–qPCR,ATAC–seq,Chip–seq,motif analysis,GSEA,data visualization,LC–MS/MS analysis,Exome sequencing,Exome data analysis, KDM6A Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs. 29735004 chr13 40553262 40555262 FOXO1 EPAC2 knockdown markedly reduced Phe-stimulated C/EBPβ and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene. human Epithelial High+Lowthroughput Exchange protein directly activated by cAMP (EPAC) promotes transcriptional activation of the decidual prolactin gene via CCAAT/enhancer-binding protein in human endometrial stromal cells 否 Other endometrial stromal cell E_01_0512 Luciferase assay,Treatment with siRNAs,RT-qPCR,Immunoblotting,Immunofluorescence,transfection, EPAC2 knockdown markedly reduced Phe-stimulated C/EBPβ and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EPAC2 knockdown markedly reduced Phe-stimulated C/EBPβ and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene. Immunohistochemical staining EPAC2 knockdown markedly reduced Phe-stimulated C/EBPβ and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene. Luciferase assay,Treatment with siRNAs,RT-qPCR,Immunoblotting,Immunofluorescence,transfection, FOXO1 EPAC2 knockdown markedly reduced Phe-stimulated C/EBPβ and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene. 29733381 chr6 108557419 108559419 FOXO3 Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility. human connective High+Lowthroughput The longevity SNP rs2802292 uncovered: HSF1 activates stress-dependent expression of FOXO3 through an intronic enhancer 是 rs2802292 Other E_01_0513 CRISPR/Cas9,Quantitative real-time PCR,Immunoblotting,Cell transfection,RNA interference,Cloning,ChIP,Luciferase assay,ChIP-loop assay,Cellular glutathione assay,DNA damage assay,Cell proliferation assay, Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility. Immunohistochemical staining Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility. CRISPR/Cas9,Quantitative real-time PCR,Immunoblotting,Cell transfection,RNA interference,Cloning,ChIP,Luciferase assay,ChIP-loop assay,Cellular glutathione assay,DNA damage assay,Cell proliferation assay, SOD2 FOXO3,HSF1,GADD45A Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility. Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility.;Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility.;Our functional studies highlighted the importance of the HSF1-FOXO3-SOD2/CAT/GADD45A cascade in cellular stress response and survival by promoting ROS detoxification, redox balance and DNA repair. Our findings suggest the existence of an HSF1-FOXO3 axis in human cells that could be involved in stress response pathways functionally regulating lifespan and disease susceptibility. 29732557 chr7 148804423 148806423 EZH2 Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. human connective High+Lowthroughput Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target 否 Conjunctival malignant melanoma (CM) E_01_0514 Immunohistochemistry (IHC) staining,Immunoblotting,Cell proliferation,colony assay,Flow cytometry,RNA isolation,cDNA synthesis,quantitative PCR, Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. Immunohistochemical staining Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. Immunohistochemistry (IHC) staining,Immunoblotting,Cell proliferation,colony assay,Flow cytometry,RNA isolation,cDNA synthesis,quantitative PCR, EZH2,CDKN1A Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM.;Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. 29731896 chr20 10635162 10637162 JAG1 Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer. human Gastric cancer High+Lowthroughput Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer 否 gastric cancer GC cell E_01_0515 siRNA transfection,RT‑qPCR,Methylation analysis,Cell proliferation assay,Western blot,Cell migration,cell invasion assays, Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer. Immunohistochemical staining Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer. siRNA transfection,RT‑qPCR,Methylation analysis,Cell proliferation assay,Western blot,Cell migration,cell invasion assays, JAG1 EZH2 Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer. Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer. 29731168 chr8 127791607 127793607 PVT1 Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements. human connective High+Lowthroughput Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element 否 mammary cancer HEK293T E_01_0516 RNA-seq,Rearrangement analysis,Hi-ChIP,UMI-4C,4C-Seq,Luciferase reporter assay,CRISPR/Cas9,4sU-labeling,JQ1 treatment,ChIP,ATAC-seq,Northern blot,Cell growth competition assay,Western blot,qRT-PCR,siRNA,ASO, Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements. Immunohistochemical staining Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements. RNA-seq,Rearrangement analysis,Hi-ChIP,UMI-4C,4C-Seq,Luciferase reporter assay,CRISPR/Cas9,4sU-labeling,JQ1 treatment,ChIP,ATAC-seq,Northern blot,Cell growth competition assay,Western blot,qRT-PCR,siRNA,ASO, PVT1 Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements. 29730385 chr19 6658582 6660582 TNFSF14 To explore signaling in melanocytes treated with TNFSF14, we performed RNA-seq and found that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling is activated by TNFSF14. Further, we observed that inhibition of NF-kB effectively blocks the hypopigmentation induced by TNFSF14. We conclude that TNFSF14 inhibits melanogenesis in melanocytes via NF-κB signaling and could be applied in the treatment of cutaneous pigment disorders. human Epithelial High+Lowthroughput TNFSF14 inhibits melanogenesis via NF-kB signaling in melanocytes 否 Skin pigmentation disturbances Normal human epidermal melanocytes E_01_0517 RNA-seq,transfection,RT-qPCR,Cell proliferation assay,Western blot, To explore signaling in melanocytes treated with TNFSF14, we performed RNA-seq and found that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling is activated by TNFSF14. Further, we observed that inhibition of NF-kB effectively blocks the hypopigmentation induced by TNFSF14. We conclude that TNFSF14 inhibits melanogenesis in melanocytes via NF-κB signaling and could be applied in the treatment of cutaneous pigment disorders. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To explore signaling in melanocytes treated with TNFSF14, we performed RNA-seq and found that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling is activated by TNFSF14. Further, we observed that inhibition of NF-kB effectively blocks the hypopigmentation induced by TNFSF14. We conclude that TNFSF14 inhibits melanogenesis in melanocytes via NF-κB signaling and could be applied in the treatment of cutaneous pigment disorders. Immunohistochemical staining To explore signaling in melanocytes treated with TNFSF14, we performed RNA-seq and found that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling is activated by TNFSF14. Further, we observed that inhibition of NF-kB effectively blocks the hypopigmentation induced by TNFSF14. We conclude that TNFSF14 inhibits melanogenesis in melanocytes via NF-κB signaling and could be applied in the treatment of cutaneous pigment disorders. RNA-seq,transfection,RT-qPCR,Cell proliferation assay,Western blot, TNFSF14 To explore signaling in melanocytes treated with TNFSF14, we performed RNA-seq and found that nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling is activated by TNFSF14. Further, we observed that inhibition of NF-kB effectively blocks the hypopigmentation induced by TNFSF14. We conclude that TNFSF14 inhibits melanogenesis in melanocytes via NF-κB signaling and could be applied in the treatment of cutaneous pigment disorders. 29728367 chr6 43180135 43182135 CUL9 We conclude that our proposed method is potentially useful and is complementary to TWAS and other standard gene- and pathway-based methods. human High+Lowthroughput Integration of Enhancer-Promoter Interactions with GWAS Summary Results Identifies Novel Schizophrenia-Associated Genes and Pathways 是 Schizophrenia (SCZ) MCF-7 cell E_01_0518 ChIA-PET,RNA-seq,GWAS,TWAS, We conclude that our proposed method is potentially useful and is complementary to TWAS and other standard gene- and pathway-based methods. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We conclude that our proposed method is potentially useful and is complementary to TWAS and other standard gene- and pathway-based methods. Immunohistochemical staining We conclude that our proposed method is potentially useful and is complementary to TWAS and other standard gene- and pathway-based methods. ChIA-PET,RNA-seq,GWAS,TWAS, CUL9,MRPL33 We conclude that our proposed method is potentially useful and is complementary to TWAS and other standard gene- and pathway-based methods.;We conclude that our proposed method is potentially useful and is complementary to TWAS and other standard gene- and pathway-based methods. 29726894 chr1 56491946 56493946 PLPP3 DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV. human High+Lowthroughput DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic programme in calcific aortic valve disease 否 Calcific aortic valve disease (cavd) HEK293T E_01_0519 Real-time PCR,Western blot,Whole-genome gene expression,DNA methylation,Pyrosequencing,ChIP,Cell Transfection,Luciferase reporter assay,Determination of alkaline phosphatase activity, DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV. Immunohistochemical staining DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV. Real-time PCR,Western blot,Whole-genome gene expression,DNA methylation,Pyrosequencing,ChIP,Cell Transfection,Luciferase reporter assay,Determination of alkaline phosphatase activity, PLPP3 DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV. 29725441 chr17 28503593 28505593 FOXN1 In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC. human Epithelial High+Lowthroughput Forkhead box N1 inhibits the progression of non-small cell lung cancer and serves as a tumor suppressor 否 Non small cell lung cancer (NSCLC) Normal human bronchial epithelial cell E_01_0520 Transfection,Western blot,RNA extraction,RT‑qPCR,Invasion assay,MTT,Quantitative chromatin immunoprecipitation (qChIP),Dual‑luciferase reporter assay, In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC. Immunohistochemical staining In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC. Transfection,Western blot,RNA extraction,RT‑qPCR,Invasion assay,MTT,Quantitative chromatin immunoprecipitation (qChIP),Dual‑luciferase reporter assay, FOXN1 EZH2 In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC. In conclusion, the present study demonstrated that FOXN1 served major roles in NSCLC proliferation and invasion by directly repressing EZH2 and β-catenin, which suggested that FOXN1 may function as a tumor suppressor in NSCLC. 29725411 chr7 148804870 148806870 EZH2 The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC. human NPC High+Lowthroughput Efficacy of extracts of Celastrus orbiculatus in suppressing migration and invasion by inhibiting the EZH2/ROCK1 signaling pathway in human nasopharyngeal carcinoma 否 Nasopharyngeal carcinoma (NPC) human NPC cell line 5-8F E_01_0521 Western blot,flow cytometry,MTS cytotoxicity assay,RT‑qPCR, The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC. Immunohistochemical staining The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC. Western blot,flow cytometry,MTS cytotoxicity assay,RT‑qPCR, ROCK1 EZH2 The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC. The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC. 29725368 chr7 45108303 45110303 Bax In the present study, diabetes complicated by MI promoted ST-segment elevation and myocardial apoptosis, increased infarct size, induced pathological changes and elevated LVEDP, CK-MB, cTnT, GRP78, CHOP, Bax, Ero1α, Ero1β and PDI; however, it decreased heart rate, LVSP and Bcl-2. Additionally, high glucose combined with hypoxic treatment reduced cell viability, induced cell cycle arrest at G1 phase, promoted cell apoptosis, and activated the GRP78/CHOP and Ero1/PDI signaling pathways, which were reversed by CHOP knockdown. Thus, CHOP may be an effective therapeutic target for the treatment of diabetes complicated by MI. mouse Myocardial High+Lowthroughput CCAAT/enhancer binding protein homologous protein knockdown alleviates hypoxia-induced myocardial injury in rat cardiomyocytes exposed to high glucose 否 Diabetes complicating myocardial infarction H9c2 cell E_01_0522 H&E staining,TUNEL assay,Western blot,ELISA,Triphenyltetrazolium chloride (TTC) staining,Hoechst 33258 staining,Cell Counting Kit‑8 (CCK‑8) assay, In the present study, diabetes complicated by MI promoted ST-segment elevation and myocardial apoptosis, increased infarct size, induced pathological changes and elevated LVEDP, CK-MB, cTnT, GRP78, CHOP, Bax, Ero1α, Ero1β and PDI; however, it decreased heart rate, LVSP and Bcl-2. Additionally, high glucose combined with hypoxic treatment reduced cell viability, induced cell cycle arrest at G1 phase, promoted cell apoptosis, and activated the GRP78/CHOP and Ero1/PDI signaling pathways, which were reversed by CHOP knockdown. Thus, CHOP may be an effective therapeutic target for the treatment of diabetes complicated by MI. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, diabetes complicated by MI promoted ST-segment elevation and myocardial apoptosis, increased infarct size, induced pathological changes and elevated LVEDP, CK-MB, cTnT, GRP78, CHOP, Bax, Ero1α, Ero1β and PDI; however, it decreased heart rate, LVSP and Bcl-2. Additionally, high glucose combined with hypoxic treatment reduced cell viability, induced cell cycle arrest at G1 phase, promoted cell apoptosis, and activated the GRP78/CHOP and Ero1/PDI signaling pathways, which were reversed by CHOP knockdown. Thus, CHOP may be an effective therapeutic target for the treatment of diabetes complicated by MI. Immunohistochemical staining In the present study, diabetes complicated by MI promoted ST-segment elevation and myocardial apoptosis, increased infarct size, induced pathological changes and elevated LVEDP, CK-MB, cTnT, GRP78, CHOP, Bax, Ero1α, Ero1β and PDI; however, it decreased heart rate, LVSP and Bcl-2. Additionally, high glucose combined with hypoxic treatment reduced cell viability, induced cell cycle arrest at G1 phase, promoted cell apoptosis, and activated the GRP78/CHOP and Ero1/PDI signaling pathways, which were reversed by CHOP knockdown. Thus, CHOP may be an effective therapeutic target for the treatment of diabetes complicated by MI. H&E staining,TUNEL assay,Western blot,ELISA,Triphenyltetrazolium chloride (TTC) staining,Hoechst 33258 staining,Cell Counting Kit‑8 (CCK‑8) assay, Bax In the present study, diabetes complicated by MI promoted ST-segment elevation and myocardial apoptosis, increased infarct size, induced pathological changes and elevated LVEDP, CK-MB, cTnT, GRP78, CHOP, Bax, Ero1α, Ero1β and PDI; however, it decreased heart rate, LVSP and Bcl-2. Additionally, high glucose combined with hypoxic treatment reduced cell viability, induced cell cycle arrest at G1 phase, promoted cell apoptosis, and activated the GRP78/CHOP and Ero1/PDI signaling pathways, which were reversed by CHOP knockdown. Thus, CHOP may be an effective therapeutic target for the treatment of diabetes complicated by MI. 29725115 chr8 17024798 17026798 MICU3 We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function. human connective High+Lowthroughput MICU3 is a tissue-specific enhancer of mitochondrial calcium uptake 否 Other E_01_0523 transfection,Co-immunoprecipitation,Aequorin measurements,SDS-PAGE,western blot,RNA extraction,reverse transcription PCR,quantitative real-time PCR,RNA-seq,bioinformatics, We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function. Immunohistochemical staining We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function. transfection,Co-immunoprecipitation,Aequorin measurements,SDS-PAGE,western blot,RNA extraction,reverse transcription PCR,quantitative real-time PCR,RNA-seq,bioinformatics, MICU3,MICU1,MICU2 We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function.;We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function.;We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function. 29721194 chr10 32265166 32267166 EPC1 Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript. human High+Lowthroughput Identification of an EPC2-PHF1 fusion transcript in low-grade endometrial stromal sarcoma 否 Endometrial stromal sarcoma (lg-ess) E_01_0524 Fluorescence in situ hybridization (FISH),Molecular genetic analyses,PCR,RT-PCR,RNA-seq, Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript. Immunohistochemical staining Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript. Fluorescence in situ hybridization (FISH),Molecular genetic analyses,PCR,RT-PCR,RNA-seq, EPC1,EPC2,PHF1,JAZF1,MEAF6,BRD8 Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript.;Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript.;Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript.;Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript.;Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript.;Involvement of the PHF1 gene in chromosomal rearrangements targeting band 6p21 has been found in LG-ESS with different partners from JAZF1 mapping in 7p15, to EPC1 from 10p11, MEAF6 from 1p34, and BRD8 from 5q31.In the present study, RNA sequencing of a LG-ESS showed a novel recombination of PHF1 with the Enhancer of Polycomb homolog 2 (EPC2). RT-PCR followed by Sanger sequencing and FISH analysis confirmed the EPC2-PHF1 fusion transcript. 29720835 chr10 88951288 88953288 FAS PE and GE efficiently inhibited adipocyte differentiation by suppressing the expression of adipogenic transcription factor CEBP-α and PPAR-γ.PE and GE significantly decreased the expression of adipogenic enzyme FAS.PE and GE increased the expression of lipid degrading enzyme HSL.Mixture of PE and GE exhibited additive or moderately synergistic effect on adipocyte differentiation and lipid accumulation. human adipose High+Lowthroughput Combination of Garcinia cambogia Extract and Pear Pomace Extract Additively Suppresses Adipogenesis and Enhances Lipolysis in 3T3-L1 Cells 否 Obesity, diabetes, hypertension, atherosclerosis, cancer 3T3-L1 cell E_01_0525 MTS‑PMS assay,Oil Red O staining,Immunocytochemistry, PE and GE efficiently inhibited adipocyte differentiation by suppressing the expression of adipogenic transcription factor CEBP-α and PPAR-γ.PE and GE significantly decreased the expression of adipogenic enzyme FAS.PE and GE increased the expression of lipid degrading enzyme HSL.Mixture of PE and GE exhibited additive or moderately synergistic effect on adipocyte differentiation and lipid accumulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PE and GE efficiently inhibited adipocyte differentiation by suppressing the expression of adipogenic transcription factor CEBP-α and PPAR-γ.PE and GE significantly decreased the expression of adipogenic enzyme FAS.PE and GE increased the expression of lipid degrading enzyme HSL.Mixture of PE and GE exhibited additive or moderately synergistic effect on adipocyte differentiation and lipid accumulation. Immunohistochemical staining PE and GE efficiently inhibited adipocyte differentiation by suppressing the expression of adipogenic transcription factor CEBP-α and PPAR-γ.PE and GE significantly decreased the expression of adipogenic enzyme FAS.PE and GE increased the expression of lipid degrading enzyme HSL.Mixture of PE and GE exhibited additive or moderately synergistic effect on adipocyte differentiation and lipid accumulation. MTS‑PMS assay,Oil Red O staining,Immunocytochemistry, FAS PE and GE efficiently inhibited adipocyte differentiation by suppressing the expression of adipogenic transcription factor CEBP-α and PPAR-γ.PE and GE significantly decreased the expression of adipogenic enzyme FAS.PE and GE increased the expression of lipid degrading enzyme HSL.Mixture of PE and GE exhibited additive or moderately synergistic effect on adipocyte differentiation and lipid accumulation. 29719267 chr17 43751286 43753286 SOST We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. human Embryonic craniofacial High+Lowthroughput High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development 否 Cleft lip, cleft palate cranial neural crest cell E_01_0526 ChIP-Seq,ChIP We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. Immunohistochemical staining We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. ChIP-Seq,ChIP SOST,PRDM16 SOX9,MYC We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. ;We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. ;We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. 29714661 chr5 88714300 88716300 MEF2C Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells. human Liver cancer High+Lowthroughput MEF2C promotes gefitinib resistance in hepatic cancer cells through regulating MIG6 transcription 否 liver cancer Hepatic cancer cell lines PHCC E_01_0527 MEF2C knockdown,Chromatin immunoprecipitation assay,Dual luciferase assay,Western blot,Real-time quantitative PCR,CCK-8 method, Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells. Immunohistochemical staining Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells. MEF2C knockdown,Chromatin immunoprecipitation assay,Dual luciferase assay,Western blot,Real-time quantitative PCR,CCK-8 method, MEF2C,EGFR Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells.;Our study provides novel insight into the regulation mechanism of MIG6 and suggests potential implications for the therapeutic strategies of gefitinib resistance through inhibiting MEF2C in hepatic cancer cells. 29714127 chr14 104767057 104769057 AKT1 The present study is a novel finding of the possible role of AKT1 mutations which might help to identify gastric cancer patients. human High+Lowthroughput Novel AKT1 mutations associated with cell-cycle abnormalities in gastric carcinoma 否 gastric cancer gastric cancer cell E_01_0528 PCR,cell-cycle analysis The present study is a novel finding of the possible role of AKT1 mutations which might help to identify gastric cancer patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study is a novel finding of the possible role of AKT1 mutations which might help to identify gastric cancer patients. Immunohistochemical staining The present study is a novel finding of the possible role of AKT1 mutations which might help to identify gastric cancer patients. PCR,cell-cycle analysis AKT1 The present study is a novel finding of the possible role of AKT1 mutations which might help to identify gastric cancer patients. 29710537 chr7 148804458 148806458 EZH2 These results demonstrated that the hsa_circ_0071589/miR-600/EZH2 axis may play critical regulatory roles in the pathogenesis of CRC and may serve as a novel therapy target in CRC. human Colon High+Lowthroughput Hsa_circ_0071589 promotes carcinogenesis via the miR-600/EZH2 axis in colorectal cancer 否 Colorectal cancer (CRC) colon cancer cell line HCT116 E_01_0529 Cell transfection, reverse transcription PCR,quantitative real-time PCR(qRT-PCR),wound-healing assay,Colony formation assay,Cell viability assay (MTT assay),Western blot,Plasmid construction,Dual luciferase activity assay,RNA immunoprecipitation (RIP) assay, These results demonstrated that the hsa_circ_0071589/miR-600/EZH2 axis may play critical regulatory roles in the pathogenesis of CRC and may serve as a novel therapy target in CRC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results demonstrated that the hsa_circ_0071589/miR-600/EZH2 axis may play critical regulatory roles in the pathogenesis of CRC and may serve as a novel therapy target in CRC. Immunohistochemical staining These results demonstrated that the hsa_circ_0071589/miR-600/EZH2 axis may play critical regulatory roles in the pathogenesis of CRC and may serve as a novel therapy target in CRC. Cell transfection, reverse transcription PCR,quantitative real-time PCR(qRT-PCR),wound-healing assay,Colony formation assay,Cell viability assay (MTT assay),Western blot,Plasmid construction,Dual luciferase activity assay,RNA immunoprecipitation (RIP) assay, EZH2 These results demonstrated that the hsa_circ_0071589/miR-600/EZH2 axis may play critical regulatory roles in the pathogenesis of CRC and may serve as a novel therapy target in CRC. 29710475 chr1 60862803 60864803 NFIA miR-200c repressed HBV replication by directly targeting NFIA, which might provide a novel therapeutic target for HBV infection. human High+Lowthroughput miR-200c targets nuclear factor IA to suppress HBV replication and gene expression via repressing HBV Enhancer I activity 否 Hepatitis B virus (HBV) chronic infection, cirrhosis, hepatocellular carcinoma 293T cell E_01_0530 qRT-PCR,Western blot,Dual-Luciferase Reporter assay,ELISA,qRCR, miR-200c repressed HBV replication by directly targeting NFIA, which might provide a novel therapeutic target for HBV infection. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq miR-200c repressed HBV replication by directly targeting NFIA, which might provide a novel therapeutic target for HBV infection. Immunohistochemical staining miR-200c repressed HBV replication by directly targeting NFIA, which might provide a novel therapeutic target for HBV infection. qRT-PCR,Western blot,Dual-Luciferase Reporter assay,ELISA,qRCR, NFIA miR-200c repressed HBV replication by directly targeting NFIA, which might provide a novel therapeutic target for HBV infection. 29709906 chr8 81476346 81478346 FABP4 DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling. human adipose High+Lowthroughput Dibenzoylmethane Suppresses Lipid Accumulation and Reactive Oxygen Species Production through Regulation of Nuclear Factor (Erythroid-Derived 2)-Like 2 and Insulin Signaling in Adipocytes 否 Other 3T3-L1 preadipocytes E_01_0531 ORO Staining,Western Blot,MTT Assay,Real Time PCR,immunoblotting, DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling. Immunohistochemical staining DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling. ORO Staining,Western Blot,MTT Assay,Real Time PCR,immunoblotting, CAT,SOD1 FABP4,KLF2 DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.;DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling. DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.;DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling. 29707136 chr3 108040485 108042485 CD47 Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. human High+Lowthroughput BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells 否 Cancer, melanoma B16-F10 cell E_01_0532 Flow Cytometry,Immunoblotting,ATP assay,In vitro phagocytosis assay,In vivo phagocytosis assay,western blot, Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. Immunohistochemical staining Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. Flow Cytometry,Immunoblotting,ATP assay,In vitro phagocytosis assay,In vivo phagocytosis assay,western blot, CALR,BNIP3 CD47 Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3.;Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. 29706346 chr1 22021633 22023633 LINC00339 Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis. human High+Lowthroughput An Osteoporosis Risk SNP at 1p36.12 Acts as an Allele-Specific Enhancer to Modulate LINC00339 Expression via Long-Range Loop Formation 是 rs6426749,rs34963268,rs6684375 Osteoporosis The hFOB 1.19 cells E_01_0533 Motif Analysis,SMR analysis,Quantitative Real-Time PCR,siRNA knocdown,shRNA Knockdown,Chromatin Immunoprecipitation (ChIP) Assay,Dual-Luciferase Reporter Assays,Site-Directed Mutagenesis,Analysis of Shared Causal Genetic Variants,AseQTL Analysis,Genotyping,Association Analysis,cis-eQTL Analysis,Hi-C,TAD Analysis,Haplotype Analysis,GWAS,CRISPR/Cas9, Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis. Immunohistochemical staining Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis. Motif Analysis,SMR analysis,Quantitative Real-Time PCR,siRNA knocdown,shRNA Knockdown,Chromatin Immunoprecipitation (ChIP) Assay,Dual-Luciferase Reporter Assays,Site-Directed Mutagenesis,Analysis of Shared Causal Genetic Variants,AseQTL Analysis,Genotyping,Association Analysis,cis-eQTL Analysis,Hi-C,TAD Analysis,Haplotype Analysis,GWAS,CRISPR/Cas9, LINC00339,CDC42 CTCF,TFAP2A Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis.;Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis. Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis.;Through an integrative functional genomic and epigenomic analyses, we prioritized rs6426749 as a potential causal SNP for osteoporosis at 1p36.12. Dual-luciferase assay and CRISPR/Cas9 experiments demonstrate that rs6426749 acts as a distal allele-specific enhancer regulating expression of a lncRNA (LINC00339)(_x0001_360 kb) via long-range chromatin loop formation and that this loop is mediated by CTCF occupied near rs6426749 and LINC00339 promoter region. Specifically, rs6426749-G allele can bind transcription factor TFAP2A, which efficiently elevates the enhancer activity and increases LINC00339 expression. Downregulation of LINC00339 significantly increases the expression of CDC42 in osteoblast cells, which is a pivotal regulator involved in bone metabolism. Our study provides mechanistic insight into how a noncoding SNP affects osteoporosis by long-range interaction, a finding that could indicate promising therapeutic targets for osteoporosis. 29704115 chr11 27652286 27654286 BDNF Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors. human / High+Lowthroughput BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H(2)S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress 否 depression E_01_0534 Western Blot,BCA assay, Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors. Immunohistochemical staining Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors. Western Blot,BCA assay, BDNF Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors. 29702085 chr17 42310982 42312982 STAT3 STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation. human Nervous High+Lowthroughput TNF-α-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IκB-NFκB and JAK-STAT3 pathways 否 Neuroinflammation brain pericyte E_01_0535 Western blot,RT-PCR, STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation. Immunohistochemical staining STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation. Western blot,RT-PCR, STAT3 STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation. 29696026 chr16 23780812 23782812 Bcl6 The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. mouse lymphoid High+Lowthroughput Allergic T(H)2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4(+) T Cells 否 asthma cD4+ T cell E_01_0536 Fluorescence-activated cell sorting(Facs) analysis,chromatin immunoprecipitation(ChIP),ELISA,retroviral Vectors With a d2EGFP reporter gene,Western Blot,OVA Challenge,Bronchoalveolar lavage (BAL),Histologic Examination,transgenic mice, The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. Immunohistochemical staining The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. Fluorescence-activated cell sorting(Facs) analysis,chromatin immunoprecipitation(ChIP),ELISA,retroviral Vectors With a d2EGFP reporter gene,Western Blot,OVA Challenge,Bronchoalveolar lavage (BAL),Histologic Examination,transgenic mice, Bcl6 The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. 29695774 chr8 7052292 7054292 DEFA5 We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD. human Colon High+Lowthroughput Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies 是 rs11676348 Inflammatory bowel disease (IBD) monocyte cells E_01_0537 CAGE assay,real-time quantitative reverse transcription polymerase chain reaction (qPCR),TSS-enhancer linkage,ChIP,RNA-seq,ChIPseq,FAIRE-seq,motif-seq, We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD. Immunohistochemical staining We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD. CAGE assay,real-time quantitative reverse transcription polymerase chain reaction (qPCR),TSS-enhancer linkage,ChIP,RNA-seq,ChIPseq,FAIRE-seq,motif-seq, DEFA5,DEFA6,REG1A,REG1B,REG3A,CLDN2,CLDN10,CLDN14,CLDN18,ST6GAL1,PF4V1,CXCL1,PF4,PPBP,CXCL5,PPBPP2,CXCL2 CLDN1,CXCL8,CXCL6,CXCL3 We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD. We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.;We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD. 29694926 chr1 207878058 207880058 CD34 In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. human connective High+Lowthroughput GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling 否 Osteoporosis E_01_0538 FACS analysis, Staining assay,Reverse transcription PCR,semi-quantitative real time PCR,Western blot,Nuclear fractionation,ELISA,siRNA-mediated β-catenin gene silencing, In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. Immunohistochemical staining In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. FACS analysis, Staining assay,Reverse transcription PCR,semi-quantitative real time PCR,Western blot,Nuclear fractionation,ELISA,siRNA-mediated β-catenin gene silencing, CD34,ACACA,DKK1,SFRP2 LPL In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling.;In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling.;In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling.;In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. 29693178 chr7 79765210 79767210 GNAI1 Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC. human Epithelial High+Lowthroughput Identifying genes as potential prognostic indicators in patients with serous ovarian cancer resistant to carboplatin using integrated bioinformatics analysis 否 Serous ovarian cancer (SOC) normal ovarian surface epithelial cells E_01_0539 Gene Ontology (GO) analysis,Immunohistochemistry (IHC) analysis,Kaplan‑Meier survival analysis,Protein‑protein interaction (PPI) network, Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC. Immunohistochemical staining Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC. Gene Ontology (GO) analysis,Immunohistochemistry (IHC) analysis,Kaplan‑Meier survival analysis,Protein‑protein interaction (PPI) network, NCAPH,AURKA GNAI1,MMP9,EZH2 Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC.;Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC. Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC.;Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC.;Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non‑structural maintenance of chromosomes (non‑SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC. 29685965 chr7 148804465 148806465 EZH2 Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. human High+Lowthroughput Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells 否 Other MDA-MB-231 E_01_0540 western blot,MTS, Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. Immunohistochemical staining Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. western blot,MTS, AEBP2,PRMT1,DOT1L EZH2,SUZ12,DNMT1 Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.;Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.;Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.;Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.;Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. 29678826 chr3 38545384 38547384 SCN5A In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription. human Myotome High+Lowthroughput RNA Binding Protein, HuR, Regulates SCN5A Expression Through Stabilizing MEF2C transcription factor mRNA 否 Other RL14 E_01_0541 Transfection,Real-Time PCR Quantification,Western Blot,Ribonucleoprotein Immunoprecipitation,Electrophoretic Mobility Shift Assay(EMSA),Chromatin Immunoprecipitation–qPCR, In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription. Immunohistochemical staining In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription. Transfection,Real-Time PCR Quantification,Western Blot,Ribonucleoprotein Immunoprecipitation,Electrophoretic Mobility Shift Assay(EMSA),Chromatin Immunoprecipitation–qPCR, SCN5A MEF2C,ELAVL1 In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription. In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription.;In conclusion, our results suggested that HuR participates in a combined network at the DNA and RNA levels that regulates SCN5A mRNA expression. HuR upregulates MEF2C mRNA expression by protecting MEF2C mRNA from degradation, and consequently, the elevated MEF2C enhances SCN5A mRNA transcription. 29670286 chr8 116843661 116845661 RAD21 Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells. human High+Lowthroughput Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells 否 Other ES cell E_01_0542 ChIP,ChIP–seq,PRO-cap,Enhancer reporter assay,CRSIPR/Cas9,qRT–PCR,RNA-seq,MeDIP–seq,4C–seq,ATAC-seq,Deep sequencing,Bioinformatic characterization of enhancers,western blot, Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells. Immunohistochemical staining Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells. ChIP,ChIP–seq,PRO-cap,Enhancer reporter assay,CRSIPR/Cas9,qRT–PCR,RNA-seq,MeDIP–seq,4C–seq,ATAC-seq,Deep sequencing,Bioinformatic characterization of enhancers,western blot, RAD21,ESRRB,NANOG,ZFX SOX2,SMAD1,E2F1,STAT3,KLF4 Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.;Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells. 29669022 chr14 37586703 37588703 FOXA1 Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies. human High+Lowthroughput DNA-mediated dimerization on a compact sequence signature controls enhancer engagement and regulation by FOXA1 是 rs541455835 Other MCF7 cell E_01_0543 DNA binding domain (DBD),EMSA (electrophoretic mobility shift assays),Fluorescence-Activated Cell Sorting (FACS),Luciferase assay,Bioinformatics analysis,ChIP-seq, Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies. Immunohistochemical staining Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies. DNA binding domain (DBD),EMSA (electrophoretic mobility shift assays),Fluorescence-Activated Cell Sorting (FACS),Luciferase assay,Bioinformatics analysis,ChIP-seq, MAPT,PVT1 FOXA1,GATA3,CTCF,MYC Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies.;Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies. Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies.;Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies.;Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies.;Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies. 29667772 chr12 2956550 2958550 TEAD4 Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial-mesenchymal transition (EMT) markers such as E-cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4-targeted microRNA, namely miR6839-3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839-3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839-3p mimics as a promising therapeutic direction. human High+Lowthroughput TEAD4 exerts pro-metastatic effects and is negatively regulated by miR6839-3p in lung adenocarcinoma progression 否 Lung adenocarcinoma (LAD) E_01_0544 Tissue microarray (TMA),immunohistochemical (IHC) staining, small interfering RNA(siRNA) transfection,Quantitative reverse transcription-PCR,MTT,Transwell assays,Western blot, Flow cytometric analyses,Luciferase activity assays, Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial-mesenchymal transition (EMT) markers such as E-cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4-targeted microRNA, namely miR6839-3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839-3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839-3p mimics as a promising therapeutic direction. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial-mesenchymal transition (EMT) markers such as E-cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4-targeted microRNA, namely miR6839-3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839-3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839-3p mimics as a promising therapeutic direction. Immunohistochemical staining Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial-mesenchymal transition (EMT) markers such as E-cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4-targeted microRNA, namely miR6839-3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839-3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839-3p mimics as a promising therapeutic direction. Tissue microarray (TMA),immunohistochemical (IHC) staining, small interfering RNA(siRNA) transfection,Quantitative reverse transcription-PCR,MTT,Transwell assays,Western blot, Flow cytometric analyses,Luciferase activity assays, TEAD4 Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial-mesenchymal transition (EMT) markers such as E-cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4-targeted microRNA, namely miR6839-3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839-3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839-3p mimics as a promising therapeutic direction. 29664056 chr1 161763600 161765600 ATF6 Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. human Epithelial High+Lowthroughput Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells 否 Other HUVECs E_01_0545 Western blot,Real‑time quantitative reverse transcription polymerase chain reaction,Caspase‑3 activity assay, Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. Immunohistochemical staining Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. Western blot,Real‑time quantitative reverse transcription polymerase chain reaction,Caspase‑3 activity assay, ATF6 Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. 29654271 chr9 36830631 36832631 PAX5 By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways. human / High+Lowthroughput Whole-genome sequencing of multiple myeloma reveals oncogenic pathways are targeted somatically through multiple mechanisms 否 Multiple myeloma (mm) E_01_0546 WGS,WES,Hi-C, By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways. Immunohistochemical staining By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways. WGS,WES,Hi-C, PAX5,IRF4,PRDM1,BCL6 By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways.;By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways.;By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways.;By employing promoter capture Hi-C in naïve B-cells, we identify cis-regulatory elements (CREs) that represent a highly enriched subset of the non-coding genome in which to search for driver mutations. We identify regulatory regions whose mutation significantly alters the expression of genes as candidate non-coding drivers, including copy number variation (CNV) at CREs of MYC and single-nucleotide variants (SNVs) in a PAX5 enhancer. To better inform the interplay between non-coding driver mutations with other driver mechanisms, and their respective roles in oncogenic pathways, we extended our analysis identifying coding drivers in 40 genes, including 11 novel candidates. We demonstrate the same pathways can be targeted by coding and non-coding mutations; exemplified by IRF4 and PRDM1, along with BCL6 and PAX5, genes that are central to plasma cell differentiation. This study reveals new insights into the complex genetic alterations driving MM development and an enhanced understanding of oncogenic pathways. 29650362 chr7 148804787 148806787 EZH2 Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours, including epithelioid sarcoma. Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours. human High+Lowthroughput Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study 否 Refractory B-cell non Hodgkin lymphoma, advanced solid tumor, epithelioid sarcoma malignant rhabdoid tumour cells E_01_0547 RNA-seq,immunohistochemistry,PCR, Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours, including epithelioid sarcoma. Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours, including epithelioid sarcoma. Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours. Immunohistochemical staining Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours, including epithelioid sarcoma. Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours. RNA-seq,immunohistochemistry,PCR, EZH2,SMARCA4 Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours, including epithelioid sarcoma. Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours.;Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell non-Hodgkin lymphoma and advanced solid tumours, including epithelioid sarcoma. Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours. 29648516 chr16 69704436 69706436 NQO1 These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia. human High+Lowthroughput The phosphodiesterase-4 inhibitor roflumilast reverts proteolysis in skeletal muscle cells of patients with COPD cachexia 否 Severe chronic obstructive pulmonary disease (COPD) Myogenic Precursor Cell E_01_0548 multi-exonic gene assay,RT-PCR,immunoblotting, These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia. Immunohistochemical staining These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia. multi-exonic gene assay,RT-PCR,immunoblotting, NQO1,GCLC,GCLM These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia.;These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia.;These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia. 29644902 chr11 1155170 1157170 MUC5AC IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells. human Epithelial High+Lowthroughput Interleukin (IL) 36 gamma induces mucin 5AC, oligomeric mucus/gel-forming expression via IL-36 receptor-extracellular signal regulated kinase 1 and 2, and p38-nuclear factor kappa-light-chain-enhancer of activated B cells in human airway epithelial cells 否 Allergic and inflammatory airway disease NCI-H292 cell E_01_0549 RT-PCR,Real-Time PCR,Enzyme-Linked Immunosorbent Assay(ELISA),Western Blot,Cell Transfection with siRNA,Immunofluorescence Staining, IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells. Immunohistochemical staining IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells. RT-PCR,Real-Time PCR,Enzyme-Linked Immunosorbent Assay(ELISA),Western Blot,Cell Transfection with siRNA,Immunofluorescence Staining, MUC5AC IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells. 29644114 chr8 127732161 127734161 MYC THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. human High+Lowthroughput Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma 否 Osteosarcoma U2OS E_01_0550 ChIP-seq,Immunohistochemistry,western blot,High throughput RNA seq,MTS assay, THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. Immunohistochemical staining THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. ChIP-seq,Immunohistochemistry,western blot,High throughput RNA seq,MTS assay, CDK6,RECQL4,WRN,BLM MYC,TGFB2,TP53,RB1,BRD4 THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.;THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. 29642935 chr7 148804872 148806872 EZH2 SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. human High+Lowthroughput SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma 否 Cholangiocarcinoma (CCA) RBE cell E_01_0551 Cell transfection,RT-qPCR,Flow cytometry,TUNEL assay,Caspase-3/9 activity assay,CCK-8 assay,immunofluorescence staining,Luciferase reporter assay,RNA immunoprecipitation (RIP) assay,Chromatin immunoprecipitation (ChIP) assay,Western blotting,immunohistochemistry (IHC) assays, SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. Immunohistochemical staining SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. Cell transfection,RT-qPCR,Flow cytometry,TUNEL assay,Caspase-3/9 activity assay,CCK-8 assay,immunofluorescence staining,Luciferase reporter assay,RNA immunoprecipitation (RIP) assay,Chromatin immunoprecipitation (ChIP) assay,Western blotting,immunohistochemistry (IHC) assays, SPRY4 EZH2,DNMT1 SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA.;SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA. 29641253 chr3 41192092 41194092 CTNNB1 The novel bidirectional hypoxia-inducible shRNA expression vector may be efficient in colorectal cancer-specific gene therapy. human High+Lowthroughput Constructing a Novel Hypoxia-Inducible Bidirectional shRNA Expression Vector for Simultaneous Gene Silencing in Colorectal Cancer Gene Therapy 否 colorectal cancer HT-29 E_01_0552 Transfection,GFP assay, qRT-PCR,Western blot, The novel bidirectional hypoxia-inducible shRNA expression vector may be efficient in colorectal cancer-specific gene therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The novel bidirectional hypoxia-inducible shRNA expression vector may be efficient in colorectal cancer-specific gene therapy. Immunohistochemical staining The novel bidirectional hypoxia-inducible shRNA expression vector may be efficient in colorectal cancer-specific gene therapy. Transfection,GFP assay, qRT-PCR,Western blot, CTNNB1 The novel bidirectional hypoxia-inducible shRNA expression vector may be efficient in colorectal cancer-specific gene therapy. 29637721 chr13 51928163 51930163 ATP7B Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation-dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing. human High+Lowthroughput Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in Wilson disease 否 Wilson disease HEK293T E_01_0553 Transfection,RT-PCR,Bioinformatics predictions,MLPA analysis, Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation-dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation-dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing. Immunohistochemical staining Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation-dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing. Transfection,RT-PCR,Bioinformatics predictions,MLPA analysis, ATP7B Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation-dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing. 29637005 chr14 100235409 100237409 YY1 In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine. human High+Lowthroughput YY1 and HDAC9c transcriptionally regulate p38-mediated mesenchymal stem cell differentiation into osteoblasts 否 Other E_01_0554 Real-time RT-PCR,Reporter gene assay,Western blot,coimmunoprecipitation (CoIP),qChIP,Lentiviral infection, In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine. Immunohistochemical staining In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine. Real-time RT-PCR,Reporter gene assay,Western blot,coimmunoprecipitation (CoIP),qChIP,Lentiviral infection, YY1,EZH2 In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine.;In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine. 29636998 chr7 148804486 148806486 EZH2 Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells. human High+Lowthroughput EZH2 promotes migration and invasion of triple-negative breast cancer cells via regulating TIMP2-MMP-2/-9 pathway 否 Triple negative breast cancer (TNBC) MDA-MB-468 E_01_0555 Cell extraction,western blot,Gene knockdown,Chromatin immunoprecipitation (ChIP) assay,RT-PCR,quantitative RT-PCR, Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells. Cell extraction,western blot,Gene knockdown,Chromatin immunoprecipitation (ChIP) assay,RT-PCR,quantitative RT-PCR, EZH2,TIMP2,MMP2,MMP9 Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells.;Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells.;Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells.;Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells. 29636889 chr12 2956797 2958797 TEAD4 Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications. human High+Lowthroughput Effect of TEAD4 on multilineage differentiation of muscle-derived stem cells 否 Other E_01_0556 Flow cytometry,immunohistochemical,histological staining,SDS-PAGE,Western blot,Quantitative RT-PCR, Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications. Immunohistochemical staining Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications. Flow cytometry,immunohistochemical,histological staining,SDS-PAGE,Western blot,Quantitative RT-PCR, CAV3,ADD1 TEAD4,TEAD1,TEAD2,TEAD3 Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications.;Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications. Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications.;Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications.;Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications.;Finally, TEAD4-KD led to the failure of adipogenesis from bMDSCs. Together, our results support that TEAD4 is essential during adipogenic differentiation of bMDSCs. It has little effect on myogenesis of bMDSCs, and does not affect ostegenesis, neurogenesis, or pancreatic differentiation of bMDSCs. Our findings will be helpful for future study on the roles of the TEAD family during differentiation of MDSCs, and for controlling MDSC differentiation for stem cell applications. 29636834 chr11 61796856 61798856 FADS1 We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans. human High+Lowthroughput Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytes 是 rs174537 Other CD4+ cells E_01_0557 PCR,GWAS,correlation analysis, We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans. Immunohistochemical staining We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans. PCR,GWAS,correlation analysis, FADS1,FADS2 We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans.;We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans. 32386462 chrX 49247713 49249713 FOXP3 We show that the activity of the master transcription factor Forkhead-box protein 3 (FOXP3) attenuates p65 phosphorylation and nuclear translocation of the NF- B proteins p50, p65 and c-Rel following activation in human Treg. human lymphoid High+Lowthroughput Attenuation of canonical NF-κB signaling maintains function and stability of human Treg 否 Immune tolerance regulatory T cell E_01_0558 Flow cytometry，RT-PCR，Western blotting We show that the activity of the master transcription factor Forkhead-box protein 3 (FOXP3) attenuates p65 phosphorylation and nuclear translocation of the NF- B proteins p50, p65 and c-Rel following activation in human Treg. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that the activity of the master transcription factor Forkhead-box protein 3 (FOXP3) attenuates p65 phosphorylation and nuclear translocation of the NF- B proteins p50, p65 and c-Rel following activation in human Treg. Immunohistochemical staining We show that the activity of the master transcription factor Forkhead-box protein 3 (FOXP3) attenuates p65 phosphorylation and nuclear translocation of the NF- B proteins p50, p65 and c-Rel following activation in human Treg. Flow cytometry，RT-PCR，Western blotting FOXP3 We show that the activity of the master transcription factor Forkhead-box protein 3 (FOXP3) attenuates p65 phosphorylation and nuclear translocation of the NF- B proteins p50, p65 and c-Rel following activation in human Treg. 32391884 chr9 127791794 127793794 FPGS The intergenic SNP rs1382539 located in a regulatory element of DHFR was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 10-8) due to suppression of enhancer activity, while rs35789560 in FPGS (p.R466C, P = 5.6 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. human blood High+Lowthroughput Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia 是 rs1382539,rs35789560 Leukemia leukocyte E_01_0559 PCR The intergenic SNP rs1382539 located in a regulatory element of DHFR was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 10-8) due to suppression of enhancer activity, while rs35789560 in FPGS (p.R466C, P = 5.6 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The intergenic SNP rs1382539 located in a regulatory element of DHFR was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 10-8) due to suppression of enhancer activity, while rs35789560 in FPGS (p.R466C, P = 5.6 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Immunohistochemical staining The intergenic SNP rs1382539 located in a regulatory element of DHFR was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 10-8) due to suppression of enhancer activity, while rs35789560 in FPGS (p.R466C, P = 5.6 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. PCR FPGS The intergenic SNP rs1382539 located in a regulatory element of DHFR was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 10-8) due to suppression of enhancer activity, while rs35789560 in FPGS (p.R466C, P = 5.6 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. 32393578 chr5 88714226 88716226 MEF2C We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein (MAP) kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). human Nervous High+Lowthroughput The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription 否 E_01_0560 quantitative real-time PCR, immunostaining, reporter gene assays, RNA sequencing We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein (MAP) kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein (MAP) kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). Immunohistochemical staining We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein (MAP) kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). quantitative real-time PCR, immunostaining, reporter gene assays, RNA sequencing MEF2C We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein (MAP) kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). 32394628 chr7 148804398 148806398 EZH2 Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) along with embryonic ectoderm development (EED) and suppressor of zeste 12 (SUZ12), which implements transcriptional repression mainly by depositing tri-methylation marks at lysine 27 of histone H3 (H3K27me3). human High+Lowthroughput Identification of catalytic and non-catalytic activity inhibitors against PRC2-EZH2 complex through multiple high-throughput screening campaigns 否 Breast cancer，prostate cancer tumor cell E_01_0561 high-throughput screening Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) along with embryonic ectoderm development (EED) and suppressor of zeste 12 (SUZ12), which implements transcriptional repression mainly by depositing tri-methylation marks at lysine 27 of histone H3 (H3K27me3). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) along with embryonic ectoderm development (EED) and suppressor of zeste 12 (SUZ12), which implements transcriptional repression mainly by depositing tri-methylation marks at lysine 27 of histone H3 (H3K27me3). Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) along with embryonic ectoderm development (EED) and suppressor of zeste 12 (SUZ12), which implements transcriptional repression mainly by depositing tri-methylation marks at lysine 27 of histone H3 (H3K27me3). high-throughput screening EZH2 Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) along with embryonic ectoderm development (EED) and suppressor of zeste 12 (SUZ12), which implements transcriptional repression mainly by depositing tri-methylation marks at lysine 27 of histone H3 (H3K27me3). 32397263 chr7 76300187 76302187 HSPB1 Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. human Epithelial High+Lowthroughput Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells 否 Skin Cancer Human skin cell E_01_0562 Flow cytometry，RT-qPCR，Western Blot Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. Immunohistochemical staining Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. Flow cytometry，RT-qPCR，Western Blot HSPB1 Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. 32398735 chr17 72118099 72120099 SOX9 Mechanistically, SOX9 may sensitize TNBC cells to THZ1, in a FOXC1-related manner, suggesting that SOX9 could be as a predictive factor of THZ1. human High+Lowthroughput SOX9 interacts with FOXC1 to activate MYC and regulate CDK7 inhibitor sensitivity in triple-negative breast cancer 否 Triple-negative breast cancer MDA-468 cell E_01_0563 Immunohistochemistry，RNA isolation，quantitative RT-PCR，Western Blot，ChIP-Seq，ChIP-PCR，Co-immunoprecipitation assays Mechanistically, SOX9 may sensitize TNBC cells to THZ1, in a FOXC1-related manner, suggesting that SOX9 could be as a predictive factor of THZ1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, SOX9 may sensitize TNBC cells to THZ1, in a FOXC1-related manner, suggesting that SOX9 could be as a predictive factor of THZ1. Immunohistochemical staining Mechanistically, SOX9 may sensitize TNBC cells to THZ1, in a FOXC1-related manner, suggesting that SOX9 could be as a predictive factor of THZ1. Immunohistochemistry，RNA isolation，quantitative RT-PCR，Western Blot，ChIP-Seq，ChIP-PCR，Co-immunoprecipitation assays SOX9 Mechanistically, SOX9 may sensitize TNBC cells to THZ1, in a FOXC1-related manner, suggesting that SOX9 could be as a predictive factor of THZ1. 32408898 chr20 34277918 34279918 AHCY The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium. human High+Lowthroughput Acquired resistance to DZNep-mediated apoptosis is associated with copy number gains of AHCY in a B-cell lymphoma model 否 B-cell lymphoma model Burkitt lymphoma cell E_01_0564 Flow cytometry，Western blotting, RNA isolation，RT-PCR，Immunohistochemistry The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium. Immunohistochemical staining The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium. Flow cytometry，Western blotting, RNA isolation，RT-PCR，Immunohistochemistry AHCY The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium. 32506582 chr8 42413974 42415974 SLC20A2 We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-offunction alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. human High+Lowthroughput Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element 否 Primary familial brain calci- fication HEK293 cell E_01_0565 RT-ddPCR We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-offunction alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-offunction alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. Immunohistochemical staining We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-offunction alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. RT-ddPCR SLC20A2 We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-offunction alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. 32506995 chr21 34785195 34787195 RUNX1 Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers. human High+Lowthroughput Epigenomics-based identification of oestrogen-regulated long noncoding RNAs in ER+ breast cancer 否 Breast Cancer MCF7 cell E_01_0566 ChIP-seq，ATAC-seq，RNA isolation，quantitative RT-PCR Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers. Immunohistochemical staining Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers. ChIP-seq，ATAC-seq，RNA isolation，quantitative RT-PCR RUNX1 Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers. 32509064 chr1 156461285 156463285 MEF2D MEF2D-mediated effects on proliferation, migration, and invasion were explored in TSCC cells after transfection with MEF2D-siRNA. human connective High+Lowthroughput Myocyte-specific enhancer factor 2D promotes tumorigenesis and progression in tongue squamous cell carcinoma 否 Tongue squamous cell carcinoma TSCC cell E_01_0567 RT-qPCR，Western blotting，IHC analysis MEF2D-mediated effects on proliferation, migration, and invasion were explored in TSCC cells after transfection with MEF2D-siRNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2D-mediated effects on proliferation, migration, and invasion were explored in TSCC cells after transfection with MEF2D-siRNA. Immunohistochemical staining MEF2D-mediated effects on proliferation, migration, and invasion were explored in TSCC cells after transfection with MEF2D-siRNA. RT-qPCR，Western blotting，IHC analysis MEF2D MEF2D-mediated effects on proliferation, migration, and invasion were explored in TSCC cells after transfection with MEF2D-siRNA. 32510323 chr16 67870486 67872486 EDC4 Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. human High+Lowthroughput A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay 否 E_01_0568 seCLIP-seq，siRNAs，RT-qPCR，Immunofluorescent staining，RNA immunoprecipitation assay Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. Immunohistochemical staining Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. seCLIP-seq，siRNAs，RT-qPCR，Immunofluorescent staining，RNA immunoprecipitation assay EDC4 Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. 32511315 chrX 15492185 15494185 ACE2 The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. human connective High+Lowthroughput Activation of the SARS-CoV-2 receptor Ace2 by cytokines through pan JAK-STAT enhancers 否 The novel coronavirus mammary alveolar cell E_01_0569 ChIP-seq，RNA-seq The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. Immunohistochemical staining The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. ChIP-seq，RNA-seq ACE2 The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. 32521278 chr3 179145107 179147107 PIK3CA Even for PIK3CA-mutated cancer, BDNF-AS overexpression is a predictive marker of endocrine resistance of HRpositive BC and indicates the application of mTOR inhibitor for reversing the resistance. human High+Lowthroughput Enhancer-Driven lncRNA BDNF-AS Induces Endocrine Resistance and Malignant Progression of Breast Cancer through the RNH1/TRIM21/mTOR Cascade 否 Breast Cancer MCF-7 cell E_01_0570 siRNA /shRNA，Quantitative RT-PCR，ChIP-sequence，Western blot，Chromatin immunoprecipitation，RNA immunoprecipitation，Immunoprecipitation，Luciferase reporter assay Even for PIK3CA-mutated cancer, BDNF-AS overexpression is a predictive marker of endocrine resistance of HRpositive BC and indicates the application of mTOR inhibitor for reversing the resistance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Even for PIK3CA-mutated cancer, BDNF-AS overexpression is a predictive marker of endocrine resistance of HRpositive BC and indicates the application of mTOR inhibitor for reversing the resistance. Immunohistochemical staining Even for PIK3CA-mutated cancer, BDNF-AS overexpression is a predictive marker of endocrine resistance of HRpositive BC and indicates the application of mTOR inhibitor for reversing the resistance. siRNA /shRNA，Quantitative RT-PCR，ChIP-sequence，Western blot，Chromatin immunoprecipitation，RNA immunoprecipitation，Immunoprecipitation，Luciferase reporter assay PIK3CA Even for PIK3CA-mutated cancer, BDNF-AS overexpression is a predictive marker of endocrine resistance of HRpositive BC and indicates the application of mTOR inhibitor for reversing the resistance. 32521813 chr10 112147455 112149455 GPAM The mRNA of PLIN2 was induced by both ATL and GER at the highest concentrations. human High+Lowthroughput The Hepatotoxicity of Alantolactone and Germacrone: Their Influence on Cholesterol and Lipid Metabolism in Differentiated HepaRG Cells 否 Metabolic dysregulation HepaRG Cell E_01_0571 Western Blotting The mRNA of PLIN2 was induced by both ATL and GER at the highest concentrations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The mRNA of PLIN2 was induced by both ATL and GER at the highest concentrations. Immunohistochemical staining The mRNA of PLIN2 was induced by both ATL and GER at the highest concentrations. Western Blotting GPAM The mRNA of PLIN2 was induced by both ATL and GER at the highest concentrations. 32320655 chr5 51380554 51382554 ISL1 Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. human High+Lowthroughput Super-Enhancer Redistribution as a Mechanism of Broad Gene Dysregulation in Repeatedly Drug-Treated Cancer Cells 否 Cancer cancer cell E_01_0572 GRO-seq, RNA-seq，RNA-seq，ChIP-seq，Western blotting，qRT_x005f_x0002_PCR，Immunofluorescent imaging，flow cytometry Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. Immunohistochemical staining Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. GRO-seq, RNA-seq，RNA-seq，ChIP-seq，Western blotting，qRT_x005f_x0002_PCR，Immunofluorescent imaging，flow cytometry ISL1 Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. 32321755 chr19 54613960 54615960 LILRB1 This region possesses multiple YY1 sites, and complexes of the promoter/enhancer combination were isolated using anti-YY1 in chromatin immunoprecipitation loop. CRISPR-mediated deletion of the 3-kb region lowers LILRB1 expression in human NKL cells. human High+Lowthroughput LILRB1 Intron 1 Has a Polymorphic Regulatory Region That Enhances Transcription in NK Cells and Recruits YY1 是 rs1061679 Autoimmune diseases NK cell E_01_0573 quantitative PCR，ChIP This region possesses multiple YY1 sites, and complexes of the promoter/enhancer combination were isolated using anti-YY1 in chromatin immunoprecipitation loop. CRISPR-mediated deletion of the 3-kb region lowers LILRB1 expression in human NKL cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This region possesses multiple YY1 sites, and complexes of the promoter/enhancer combination were isolated using anti-YY1 in chromatin immunoprecipitation loop. CRISPR-mediated deletion of the 3-kb region lowers LILRB1 expression in human NKL cells. Immunohistochemical staining This region possesses multiple YY1 sites, and complexes of the promoter/enhancer combination were isolated using anti-YY1 in chromatin immunoprecipitation loop. CRISPR-mediated deletion of the 3-kb region lowers LILRB1 expression in human NKL cells. quantitative PCR，ChIP LILRB1 This region possesses multiple YY1 sites, and complexes of the promoter/enhancer combination were isolated using anti-YY1 in chromatin immunoprecipitation loop. CRISPR-mediated deletion of the 3-kb region lowers LILRB1 expression in human NKL cells. 32321757 chr17 39755055 39757055 IKZF3 Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. human lymphoid High+Lowthroughput IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4(+) T Cells 否 Inflammatory CD4 + T cell E_01_0574 Flow cytometry，RNA isolation，Luciferase assay，quantitative PCR Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. Immunohistochemical staining Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. Flow cytometry，RNA isolation，Luciferase assay，quantitative PCR IKZF3 Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. 32323737 chr17 42310954 42312954 STAT3 SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3-specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. human High+Lowthroughput Downregulation of SETD7 promotes migration and invasion of lung cancer cells via JAK2/STAT3 pathway 否 Lung cancer Lung cancer cell E_01_0575 siRNA，RT‑qPCR，Western blot SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3-specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3-specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. Immunohistochemical staining SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3-specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. siRNA，RT‑qPCR，Western blot STAT3 SETD7 knockdown activated the Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling pathway and enhanced lung cancer cell migration, whereas the STAT3-specific inhibitor Stattic abrogated the effect of SETD7 on cell migration. Taken together, these data indicated that SETD7 acts as a tumor suppressor, and the reduced expression of SETD7 may contribute to lung cancer progression. 32326648 chr3 12285010 12287010 PPARG While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). human High+Lowthroughput The Expression Profile of Dental Pulp-Derived Stromal Cells Supports Their Limited Capacity to Differentiate into Adipogenic Cells 否 Adipogenesis E_01_0576 Immunophenotypic Characterisation，RT-PCR，qRT-PCR，RNA Seq While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). Immunohistochemical staining While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). Immunophenotypic Characterisation，RT-PCR，qRT-PCR，RNA Seq PPARG While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). 32328192 chr19 15825511 15827511 UCA1 Moreover, overexpression of UCA1 promotes GC cell proliferation and inhibits cisplatin-induced apoptosis. Knockdown of UCA1 showed the opposite results. Besides, UCA1 exerted its function through interacting with EZH2 and regulates EZH2 expression, knockdown of EZH2 decreased cisplatin resistance of GC cells. human High+Lowthroughput LncRNA UCA1 promotes cisplatin resistance in gastric cancer via recruiting EZH2 and activating PI3K/AKT pathway 否 Gastric cancer GC cell E_01_0577 qRT-PCR，CCK-8 Assay，Western blot，RNA immunoprecipitation， Moreover, overexpression of UCA1 promotes GC cell proliferation and inhibits cisplatin-induced apoptosis. Knockdown of UCA1 showed the opposite results. Besides, UCA1 exerted its function through interacting with EZH2 and regulates EZH2 expression, knockdown of EZH2 decreased cisplatin resistance of GC cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, overexpression of UCA1 promotes GC cell proliferation and inhibits cisplatin-induced apoptosis. Knockdown of UCA1 showed the opposite results. Besides, UCA1 exerted its function through interacting with EZH2 and regulates EZH2 expression, knockdown of EZH2 decreased cisplatin resistance of GC cells. Immunohistochemical staining Moreover, overexpression of UCA1 promotes GC cell proliferation and inhibits cisplatin-induced apoptosis. Knockdown of UCA1 showed the opposite results. Besides, UCA1 exerted its function through interacting with EZH2 and regulates EZH2 expression, knockdown of EZH2 decreased cisplatin resistance of GC cells. qRT-PCR，CCK-8 Assay，Western blot，RNA immunoprecipitation， UCA1 Moreover, overexpression of UCA1 promotes GC cell proliferation and inhibits cisplatin-induced apoptosis. Knockdown of UCA1 showed the opposite results. Besides, UCA1 exerted its function through interacting with EZH2 and regulates EZH2 expression, knockdown of EZH2 decreased cisplatin resistance of GC cells. 32332020 chr20 44352418 44354418 HNF4A Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of Interleukin signaling, in a lineage-specific manner. human High+Lowthroughput Lineage-Specific Epigenomic and Genomic Activation of Oncogene HNF4A Promotes Gastrointestinal Adenocarcinomas 否 Gastrointestinal adenocarcinomas Eso26 cell E_01_0578 ELMER analyses，ChIP，Immunohistochemistry，4C-Seq Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of Interleukin signaling, in a lineage-specific manner. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of Interleukin signaling, in a lineage-specific manner. Immunohistochemical staining Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of Interleukin signaling, in a lineage-specific manner. ELMER analyses，ChIP，Immunohistochemistry，4C-Seq HNF1A Functionally, HNF4A promoted cancer proliferation and survival by transcriptional activation of many downstream targets, including HNF1A and factors of Interleukin signaling, in a lineage-specific manner. 32333502 chr14 37586766 37588766 FOXA1 Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1 and BRD4 binding. human High+Lowthroughput Darolutamide antagonizes androgen signaling by blocking enhancer and super-enhancer activation 否 Prostate cancer VCaP cell E_01_0579 RNA isolation，RNA-seq， ChIP seq，ChIP-seq， Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1 and BRD4 binding. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1 and BRD4 binding. Immunohistochemical staining Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1 and BRD4 binding. RNA isolation，RNA-seq， ChIP seq，ChIP-seq， FOXA1 Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1 and BRD4 binding. 32340270 chr1 161763935 161765935 ATF6 IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). human High+Lowthroughput Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways 否 Ischemia THP-1 cells E_01_0580 Quantitative Real-Time PCR，Western Blot IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Immunohistochemical staining IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Quantitative Real-Time PCR，Western Blot ATF6 IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). 32343676 chr14 37586949 37588949 FOXA1 These transcriptional hubs operate within the framework set by structural proteins CTCF and cohesins and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. human High+Lowthroughput The landscape of RNA polymerase II-associated chromatin interactions in prostate cancer 是 rs684232 Prostate cancer prostate cell E_01_0581 ChIA-PET， These transcriptional hubs operate within the framework set by structural proteins CTCF and cohesins and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These transcriptional hubs operate within the framework set by structural proteins CTCF and cohesins and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. Immunohistochemical staining These transcriptional hubs operate within the framework set by structural proteins CTCF and cohesins and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. ChIA-PET， FOXA1,FOXA2 These transcriptional hubs operate within the framework set by structural proteins CTCF and cohesins and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1.;These transcriptional hubs operate within the framework set by structural proteins CTCF and cohesins and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA2. 32346422 chr19 15825536 15827536 UCA1 Finally, overexpression of MMP9 reversed the decreased proliferative and migratory abilities in ox-LDL-treated VSMCs overexpressing UCA1. human Musculature High+Lowthroughput Downregulated lncRNA UCA1 accelerates proliferation and migration of vascular smooth muscle cells by epigenetic regulation of MMP9 否 blood vessel smooth muscle cell E_01_0582 qRT-PCR，Western blot，Immunofluorescence，ChIP，RNA immunoprecipitation，Western blotting Finally, overexpression of MMP9 reversed the decreased proliferative and migratory abilities in ox-LDL-treated VSMCs overexpressing UCA1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, overexpression of MMP9 reversed the decreased proliferative and migratory abilities in ox-LDL-treated VSMCs overexpressing UCA1. Immunohistochemical staining Finally, overexpression of MMP9 reversed the decreased proliferative and migratory abilities in ox-LDL-treated VSMCs overexpressing UCA1. qRT-PCR，Western blot，Immunofluorescence，ChIP，RNA immunoprecipitation，Western blotting UCA1 Finally, overexpression of MMP9 reversed the decreased proliferative and migratory abilities in ox-LDL-treated VSMCs overexpressing UCA1. 32348926 chr17 72118143 72120143 SOX9 Endocrine differentiation of hPPs was affected, as indicated by neurogenin-3 (NGN3) downregulation, owing to abnormal increases in SOX9 and hairy and enhancer of split-1(HES1) expression. human High+Lowthroughput Effects of per- and poly-fluorinated alkyl substances on pancreatic and endocrine differentiation of human pluripotent stem cells 否 pancreatic A cell E_01_0583 qRT-PCR，Western blot， Immunofluorescence Endocrine differentiation of hPPs was affected, as indicated by neurogenin-3 (NGN3) downregulation, owing to abnormal increases in SOX9 and hairy and enhancer of split-1(HES1) expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Endocrine differentiation of hPPs was affected, as indicated by neurogenin-3 (NGN3) downregulation, owing to abnormal increases in SOX9 and hairy and enhancer of split-1(HES1) expression. Immunohistochemical staining Endocrine differentiation of hPPs was affected, as indicated by neurogenin-3 (NGN3) downregulation, owing to abnormal increases in SOX9 and hairy and enhancer of split-1(HES1) expression. qRT-PCR，Western blot， Immunofluorescence SOX9 Endocrine differentiation of hPPs was affected, as indicated by neurogenin-3 (NGN3) downregulation, owing to abnormal increases in SOX9 and hairy and enhancer of split-1(HES1) expression. 32362325 chrX 49247655 49249655 FOXP3 Thus, naive Treg cell-specific CpG hypomethylation had a key role in controlling Treg cell-specific gene transcription and epigenetic modification. human High+Lowthroughput Regulatory T Cell-Specific Epigenomic Region Variants Are a Key Determinant of Susceptibility to Common Autoimmune Diseases 是 rs231735,rs1024161,rs3087243 Autoimmune Diseases T cell E_01_0584 PBAT-seq, ChIP-seq, ATAC-seq,RNA-seq Thus, naive Treg cell-specific CpG hypomethylation had a key role in controlling Treg cell-specific gene transcription and epigenetic modification. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, naive Treg cell-specific CpG hypomethylation had a key role in controlling Treg cell-specific gene transcription and epigenetic modification. Immunohistochemical staining Thus, naive Treg cell-specific CpG hypomethylation had a key role in controlling Treg cell-specific gene transcription and epigenetic modification. PBAT-seq, ChIP-seq, ATAC-seq,RNA-seq FOXP3 Thus, naive Treg cell-specific CpG hypomethylation had a key role in controlling Treg cell-specific gene transcription and epigenetic modification. 32366581 chr1 167050287 167052287 GPA33 GPA33 identifies Treg cells in human blood that lack the ability to produce effector cytokines (IL-2, IFN-g, IL-17), regardless of differentiation stage. human lymphoid High+Lowthroughput GPA33: A Marker to Identify Stable Human Regulatory T Cells 否 T cell E_01_0585 ， mRNA seq GPA33 identifies Treg cells in human blood that lack the ability to produce effector cytokines (IL-2, IFN-g, IL-17), regardless of differentiation stage. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GPA33 identifies Treg cells in human blood that lack the ability to produce effector cytokines (IL-2, IFN-g, IL-17), regardless of differentiation stage. Immunohistochemical staining GPA33 identifies Treg cells in human blood that lack the ability to produce effector cytokines (IL-2, IFN-g, IL-17), regardless of differentiation stage. ， mRNA seq GPA33 GPA33 identifies Treg cells in human blood that lack the ability to produce effector cytokines (IL-2, IFN-g, IL-17), regardless of differentiation stage. 32368395 chr7 148804495 148806495 EZH2 We further demonstrated that CDK2 inhibitor is a more promising agent than EZH2 inhibitor in repressing TNBC and HGSOC due to a feedback increase in CDK2 activity by EZH2 inhibitor. human High+Lowthroughput Inhibition of CDK2 reduces EZH2 phosphorylation and reactivates ERα expression in high-grade serous ovarian carcinoma 否 High-grade serous ovarian carcinoma Triple-negative breast cancer cell E_01_0586 ，Immunoblotting analysis We further demonstrated that CDK2 inhibitor is a more promising agent than EZH2 inhibitor in repressing TNBC and HGSOC due to a feedback increase in CDK2 activity by EZH2 inhibitor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We further demonstrated that CDK2 inhibitor is a more promising agent than EZH2 inhibitor in repressing TNBC and HGSOC due to a feedback increase in CDK2 activity by EZH2 inhibitor. Immunohistochemical staining We further demonstrated that CDK2 inhibitor is a more promising agent than EZH2 inhibitor in repressing TNBC and HGSOC due to a feedback increase in CDK2 activity by EZH2 inhibitor. ，Immunoblotting analysis EZH2 We further demonstrated that CDK2 inhibitor is a more promising agent than EZH2 inhibitor in repressing TNBC and HGSOC due to a feedback increase in CDK2 activity by EZH2 inhibitor. 32376288 chr17 48721672 48723672 HOXB13 Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. human High+Lowthroughput HOXB13 controls cell state through super-enhancers 否 Malignant rhabdoid tumor Rhabdomyoid tumor cell E_01_0587 ChIP assay，qRT-PCR Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. Immunohistochemical staining Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. ChIP assay，qRT-PCR HOXB13 Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. 32376693 chr12 57456839 57458839 GLI1 Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) to these elements. human High+Lowthroughput The transcription factor GLI1 cooperates with the chromatin remodeler SMARCA2 to regulate chromatin accessibility at distal DNA regulatory elements 否 Multiple malignancies General Cell E_01_0588 RNA-seq，ATAC-seq，RNA isolation，Immunoprecipations Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) to these elements. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) to these elements. Immunohistochemical staining Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) to these elements. RNA-seq，ATAC-seq，RNA isolation，Immunoprecipations GLI1 Here, we provide evidence that GLI1 controls chromatin accessibility at distal regulatory regions by modulating the recruitment of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) to these elements. 32378752 chr1 8001410 8003410 ERRFI1 By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. human High+Lowthroughput Long noncoding RNA ANRIL promotes the malignant progression of cholangiocarcinoma by epigenetically repressing ERRFI1 expression 否 Cholangiocarcinoma CCA cell E_01_0589 qRT-PCR，Flow cytometric，Chromatin immunoprecipitation assays，Western blot By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. Immunohistochemical staining By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. qRT-PCR，Flow cytometric，Chromatin immunoprecipitation assays，Western blot ERRFI1 By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2), ANRIL could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 (ERRFI1), which is a tumor suppressor gene in CCA. 32384149 chr13 28000167 28002167 FLT3 Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the PI3K/AKT, RAS/MAPK and STAT5 signaling pathways. human High+Lowthroughput 13q12.2 deletions in acute lymphoblastic leukemia lead to upregulation of FLT3 through enhancer hijacking 有 Acute lymphoblastic leukemia HEK293T E_01_0590 RNA-seq Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the PI3K/AKT, RAS/MAPK and STAT5 signaling pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the PI3K/AKT, RAS/MAPK and STAT5 signaling pathways. Immunohistochemical staining Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the PI3K/AKT, RAS/MAPK and STAT5 signaling pathways. RNA-seq FLT3 Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the PI3K/AKT, RAS/MAPK and STAT5 signaling pathways. 32409685 chr2 15937714 15939714 MYCN We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. human Nervous High+Lowthroughput MYC transcription activation mediated by OCT4 as a mechanism of resistance to 13-cisRA-mediated differentiation in neuroblastoma 否 Neuroblastoma neuroblastoma cell E_01_0591 Immunoblotting，immunoprecipitation，RT-PCR，ChIP We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. Immunohistochemical staining We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. Immunoblotting，immunoprecipitation，RT-PCR，ChIP MYCN We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. 32427048 chr19 18371889 18373889 GDF15 Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels. human High+Lowthroughput Noncoding SNPs associated with increased GDF15 levels located in a metformin-activated enhancer region upstream of GDF15 是 rs888663,rs62122429,rs4808791 Type 2 diabetes HepG2 cell E_01_0592 ChIP-seq Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels. Immunohistochemical staining Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels. ChIP-seq GDF15 Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels. 32432037 chr9 81580658 81582658 TLE1 Our findings showed that TLE1 expression was common in PDAC cell lines. human High+Lowthroughput Transducin-Like Enhancer of Split-1 Inhibits Malignant Behaviors in vitro and Predicts a Better Prognosis in Pancreatic Ductal Adenocarcinoma 否 Pancreatic Ductal Adenocarcinoma PDAC E_01_0593 Western Blot，RNA Isolation，Real-Time Polymerase Chain Reaction，RNA Seq，Immunohistochemistry Our findings showed that TLE1 expression was common in PDAC cell lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings showed that TLE1 expression was common in PDAC cell lines. Immunohistochemical staining Our findings showed that TLE1 expression was common in PDAC cell lines. Western Blot，RNA Isolation，Real-Time Polymerase Chain Reaction，RNA Seq，Immunohistochemistry TLE1 Our findings showed that TLE1 expression was common in PDAC cell lines. 32432675 chr1 8002032 8004032 ERRFI1 Taken together, our findings suggest that the progressive loss of the GC-dependent regulation and anti-tumorigenic function of ERRFI1 influences BCa progression and may contribute to the unfavorable effects of GC therapy in TNBC. human epithelial cells High+Lowthroughput Differential Glucocorticoid-Dependent Regulation and Function of the ERRFI1 Gene in Triple-Negative Breast Cancer 否 Triple-Negative Breast Cancer MCF10A cell E_01_0594 qPCR，ChIP-seq Taken together, our findings suggest that the progressive loss of the GC-dependent regulation and anti-tumorigenic function of ERRFI1 influences BCa progression and may contribute to the unfavorable effects of GC therapy in TNBC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, our findings suggest that the progressive loss of the GC-dependent regulation and anti-tumorigenic function of ERRFI1 influences BCa progression and may contribute to the unfavorable effects of GC therapy in TNBC. Immunohistochemical staining Taken together, our findings suggest that the progressive loss of the GC-dependent regulation and anti-tumorigenic function of ERRFI1 influences BCa progression and may contribute to the unfavorable effects of GC therapy in TNBC. qPCR，ChIP-seq ERRFI1 Taken together, our findings suggest that the progressive loss of the GC-dependent regulation and anti-tumorigenic function of ERRFI1 influences BCa progression and may contribute to the unfavorable effects of GC therapy in TNBC. 32442411 chr4 176680985 176682985 VEGFC Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. human Epithelial High+Lowthroughput Systems Genetics in Human Endothelial Cells Identifies Non-coding Variants Modifying Enhancers, Expression, and Complex Disease Traits 是 rs12028528,rs7975658,rs6825977,rs17114036 aortic endothelial cell E_01_0595 High-throughput Seq，eQTL Analysis，ChIP-seq，ATAC-seq， Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. Immunohistochemical staining Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. High-throughput Seq，eQTL Analysis，ChIP-seq，ATAC-seq， FGD6,KIF26B VEGFC Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B.;Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. Using CRISPR interference (CRISPRi), allele-specific reporter assays, and chromatin conformation capture, we validated candidate enhancer variants located up to 750 kb from their target genes, VEGFC, FGD6, and KIF26B. 32453339 chr7 148804304 148806304 EZH2 We found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. human connective High+Lowthroughput USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells 否 Prostate cancer HEK293T E_01_0596 Real-time RT-PCR， We found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. Immunohistochemical staining We found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. Real-time RT-PCR， EZH2 We found that the enhancer of zeste homolog 2 (EZH2), which catalyzes the methylation at lysine 27 of histone H3, is a target of USP7 and is stabilized by USP7-mediated deubiquitination. 32457600 chr22 42123282 42125282 CYP2D6 Results: Phasing predicted that the enhancer SNP can occur on numerous CYP2D6 haplotypes including CYP2D6*1, *2, *5, and *41 and suggested that linkage is incomplete, i.e., a portion of these alleles do not have the enhancer SNP. human connective High+Lowthroughput "Long-Distance Phasing of a Tentative ""Enhancer"" Single-Nucleotide Polymorphism With CYP2D6 Star Allele Definitions" 是 rs5758550,rs16947 Liver Tissue Cell E_01_0597 PCR Results: Phasing predicted that the enhancer SNP can occur on numerous CYP2D6 haplotypes including CYP2D6*1, *2, *5, and *41 and suggested that linkage is incomplete, i.e., a portion of these alleles do not have the enhancer SNP. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results: Phasing predicted that the enhancer SNP can occur on numerous CYP2D6 haplotypes including CYP2D6*1, *2, *5, and *41 and suggested that linkage is incomplete, i.e., a portion of these alleles do not have the enhancer SNP. Immunohistochemical staining Results: Phasing predicted that the enhancer SNP can occur on numerous CYP2D6 haplotypes including CYP2D6*1, *2, *5, and *41 and suggested that linkage is incomplete, i.e., a portion of these alleles do not have the enhancer SNP. PCR CYP2D6 Results: Phasing predicted that the enhancer SNP can occur on numerous CYP2D6 haplotypes including CYP2D6*1, *2, *5, and *41 and suggested that linkage is incomplete, i.e., a portion of these alleles do not have the enhancer SNP. 32461377 chr10 8042505 8044505 GATA3 Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. human High+Lowthroughput Long noncoding RNA lnc-LOC645166 promotes adriamycin resistance via NF-κB/GATA3 axis in breast cancer 否 Breast cancer MDA-MB-231 cell E_01_0598 RT-qPCR,Flow cytometric analysis,Western blot,Chromatin immunoprecipitation assays Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. Immunohistochemical staining Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. RT-qPCR,Flow cytometric analysis,Western blot,Chromatin immunoprecipitation assays GATA3 Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) demonstrated that lncRNA LOC645166 could increase the expression of GATA binding protein 3 (GATA3) via binding with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), leading to the activation of STAT3 and promoting chemoresistance in breast cancer. 32464274 chr5 177083579 177085579 FGFR4 These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. human Musculature High+Lowthroughput Molecular mechanisms of Guadecitabine induced FGFR4 down regulation in alveolar rhabdomyosarcomas 否 Alveolar rhabdomyosarcomas RH30 cell E_01_0599 Real-Time RT-PCR quantification,ChIP-seq,Immunoblotting,Immunocytochemistry These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. Immunohistochemical staining These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. Real-Time RT-PCR quantification,ChIP-seq,Immunoblotting,Immunocytochemistry FGFR4 These changes were associated with a significant reduction in FGFR4 transcript levels in treated cells. These decreases in H3K4me1 in the FGFR4 super enhancer were also associated with a 240-fold increase in KDM5B (JARID1B) mRNA levels. 32467994 chr1 173856174 173858174 GAS5 The results showed that HG treatment induced ER stress in ARPE 19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p) protein kinase R like ER kinase, p eukaryotic initiation factor 2α, activating transcription factor 4 and CCAAT/enhancer-binding protein homologous protein. human Epithelial High+Lowthroughput LncRNA GAS5 suppresses ER stress?induced apoptosis and inflammation by regulating SERCA2b in HG?treated retinal epithelial cell 否 Inflammation ARPE 19 cell E_01_0600 RT‑qPCR，Western blot，Flow cytometry The results showed that HG treatment induced ER stress in ARPE 19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p) protein kinase R like ER kinase, p eukaryotic initiation factor 2α, activating transcription factor 4 and CCAAT/enhancer-binding protein homologous protein. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results showed that HG treatment induced ER stress in ARPE 19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p) protein kinase R like ER kinase, p eukaryotic initiation factor 2α, activating transcription factor 4 and CCAAT/enhancer-binding protein homologous protein. Immunohistochemical staining The results showed that HG treatment induced ER stress in ARPE 19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p) protein kinase R like ER kinase, p eukaryotic initiation factor 2α, activating transcription factor 4 and CCAAT/enhancer-binding protein homologous protein. RT‑qPCR，Western blot，Flow cytometry GAS5 The results showed that HG treatment induced ER stress in ARPE 19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p) protein kinase R like ER kinase, p eukaryotic initiation factor 2α, activating transcription factor 4 and CCAAT/enhancer-binding protein homologous protein. 32471508 chr1 181086111 181088111 IER5 PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. human Epithelial High+Lowthroughput Novel role of PAF1 in attenuating radiosensitivity in cervical cancer by inhibiting IER5 transcription 否 Cervical cancer Siha cell E_01_0601 siRNAs，Western blotting，qRT-PCR，Immunohistochemistry，Immunofluorescence analysis，Flow cytometry，ChIP-qPCR PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. Immunohistochemical staining PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. siRNAs，Western blotting，qRT-PCR，Immunohistochemistry，Immunofluorescence analysis，Flow cytometry，ChIP-qPCR IER5 PAF1 reduces CC radiosensitivity by inhibiting IER5 transcription, at least in part by regulating its enhancers. 32478125 chr1 207877984 207879984 CD34 Notably, similar editing improvement was observed when excess gRNA over Cas9 protein was used, providing a DNAfree alternative suitable for therapeutic applications. human High+Lowthroughput Increasing CRISPR Efficiency and Measuring Its Specificity in HSPCs Using a Clinically Relevant System 否 hematopoietic stem and progenitor cell E_01_0602 GUIDE-Seq，rhAmpSeq Notably, similar editing improvement was observed when excess gRNA over Cas9 protein was used, providing a DNAfree alternative suitable for therapeutic applications. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Notably, similar editing improvement was observed when excess gRNA over Cas9 protein was used, providing a DNAfree alternative suitable for therapeutic applications. Immunohistochemical staining Notably, similar editing improvement was observed when excess gRNA over Cas9 protein was used, providing a DNAfree alternative suitable for therapeutic applications. GUIDE-Seq，rhAmpSeq CD34 Notably, similar editing improvement was observed when excess gRNA over Cas9 protein was used, providing a DNAfree alternative suitable for therapeutic applications. 32488243 chr1 247413679 247415679 NLRP3 Specific involvement of NLRP3 inflammasome activation in IL-1beta and IL-18 release after hormone withdrawal was investigated via application of the NLRP3 inflammasome inhibitor MCC950 at the time of hormone withdrawal. human connective High+Lowthroughput Endometrial inflammasome activation accompanies menstruation and may have implications for systemic inflammatory events of the menstrual cycle 否 Endometrial inflammasome activation accompanies endometrial stromal cell E_01_0603 Immunohistochemistry，Fluorescent immunohistochemistry，Western immunoblotting Specific involvement of NLRP3 inflammasome activation in IL-1beta and IL-18 release after hormone withdrawal was investigated via application of the NLRP3 inflammasome inhibitor MCC950 at the time of hormone withdrawal. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Specific involvement of NLRP3 inflammasome activation in IL-1beta and IL-18 release after hormone withdrawal was investigated via application of the NLRP3 inflammasome inhibitor MCC950 at the time of hormone withdrawal. Immunohistochemical staining Specific involvement of NLRP3 inflammasome activation in IL-1beta and IL-18 release after hormone withdrawal was investigated via application of the NLRP3 inflammasome inhibitor MCC950 at the time of hormone withdrawal. Immunohistochemistry，Fluorescent immunohistochemistry，Western immunoblotting NLRP3 Specific involvement of NLRP3 inflammasome activation in IL-1beta and IL-18 release after hormone withdrawal was investigated via application of the NLRP3 inflammasome inhibitor MCC950 at the time of hormone withdrawal. 32489294 chr9 136879139 136881139 TRAF2 TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. human High+Lowthroughput Molecular cloning, expression, overproduction and characterization of human TRAIP Leucine zipper protein 否 Apoptosis E_01_0604 PCR TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. Immunohistochemical staining TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. PCR TRAF2 TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. 32499643 chr8 127733096 127735096 MYC Furthermore, we show that CCAT1-5L a super-enhancer hub RNA interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. human High+Lowthroughput RIC-seq for global in situ profiling of RNA-RNA spatial interactions 否 Cancer HeLa cell E_01_0605 RIC-seq Furthermore, we show that CCAT1-5L a super-enhancer hub RNA interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, we show that CCAT1-5L a super-enhancer hub RNA interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. Immunohistochemical staining Furthermore, we show that CCAT1-5L a super-enhancer hub RNA interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. RIC-seq MYC Furthermore, we show that CCAT1-5L a super-enhancer hub RNA interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. 32505533 chr7 148804812 148806812 EZH2 Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. human connective High+Lowthroughput Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma 否 Human intrahepatic cholangiocarcinoma stromal cell E_01_0606 scRNA-seq Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. Immunohistochemical staining Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. scRNA-seq EZH2 Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. 32522577 chr3 97762164 97764164 ARL6 Reduced-expression of miR-143-3p enhanced the CdCl2-induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/β-catenin pathway, effects that were reversed by down-regulated expression of ARL6. human High+Lowthroughput MircoRNA-143-3p regulating ARL6 is involved in the cadmium-induced inhibition of osteogenic differentiation in human bone marrow mesenchymal stem cells 否 E_01_0607 QRT-PCR，RT-PCR，Western blots， Luciferase reporter assays Reduced-expression of miR-143-3p enhanced the CdCl2-induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/β-catenin pathway, effects that were reversed by down-regulated expression of ARL6. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Reduced-expression of miR-143-3p enhanced the CdCl2-induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/β-catenin pathway, effects that were reversed by down-regulated expression of ARL6. Immunohistochemical staining Reduced-expression of miR-143-3p enhanced the CdCl2-induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/β-catenin pathway, effects that were reversed by down-regulated expression of ARL6. QRT-PCR，RT-PCR，Western blots， Luciferase reporter assays ARL6 Reduced-expression of miR-143-3p enhanced the CdCl2-induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/β-catenin pathway, effects that were reversed by down-regulated expression of ARL6. 32527767 chr13 23178617 23180617 SGCG Concordantly, rs679482-A impairs native repressor activity and increases basal and DMRT2 mediated enhancer activity. human High+Lowthroughput SGCG rs679482 Associates With Weight Loss Success in Response to an Intensively Supervised Outpatient Program 是 rs679482 Fat C2C12 cell E_01_0608 Genome-wide association analysis,ChIP Concordantly, rs679482-A impairs native repressor activity and increases basal and DMRT2 mediated enhancer activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Concordantly, rs679482-A impairs native repressor activity and increases basal and DMRT2 mediated enhancer activity. Immunohistochemical staining Concordantly, rs679482-A impairs native repressor activity and increases basal and DMRT2 mediated enhancer activity. Genome-wide association analysis,ChIP SGCG Concordantly, rs679482-A impairs native repressor activity and increases basal and DMRT2 mediated enhancer activity. 32533263 chr7 87500642 87502642 ABCB1 ased on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. human High+Lowthroughput Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy 否 Vero E6 cell E_01_0609 ased on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ased on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. Immunohistochemical staining ased on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. ABCB1 ased on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. 32537408 chr7 148804294 148806294 EZH2 LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression human connective High+Lowthroughput LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression 否 Urothelial cancer hepatocyte E_01_0610 qRT-PCR，Western blot，flow cytometry LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression Immunohistochemical staining LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression qRT-PCR，Western blot，flow cytometry EZH2 LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression 32548603 chr3 181708842 181710842 SOX2 In these regions, the C/EBP motif regulates HIOEC specific enhancer and regulates SOX2 and PITX2, thereby promoting wound healing of oral keratinocytes. human Epithelial High+Lowthroughput Intrinsic Differences between the Open Chromatin Regions of Oral and Epidermal Keratinocytes 否 E_01_0611 ATAC-seq In these regions, the C/EBP motif regulates HIOEC specific enhancer and regulates SOX2 and PITX2, thereby promoting wound healing of oral keratinocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In these regions, the C/EBP motif regulates HIOEC specific enhancer and regulates SOX2 and PITX2, thereby promoting wound healing of oral keratinocytes. Immunohistochemical staining In these regions, the C/EBP motif regulates HIOEC specific enhancer and regulates SOX2 and PITX2, thereby promoting wound healing of oral keratinocytes. ATAC-seq SOX2 In these regions, the C/EBP motif regulates HIOEC specific enhancer and regulates SOX2 and PITX2, thereby promoting wound healing of oral keratinocytes. 32552749 chr4 73992599 73994599 CXCL5 Conditioned media of endometrial niche cells cocultured with eMSCs contained increased levels of C-X-C motif ligand 1 (CXCL1), CXCL5 and interleukin 6. human Epithelial High+Lowthroughput Understanding the regulatory mechanisms of endometrial cells on activities of endometrial mesenchymal stem-like cells during menstruation 否 Menstruation isolation procedure of endometrial cell E_01_0612 Western blot,Flow cytometry,Qrt-PCR,WNT reporter assay,Immunofluorescence Conditioned media of endometrial niche cells cocultured with eMSCs contained increased levels of C-X-C motif ligand 1 (CXCL1), CXCL5 and interleukin 6. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conditioned media of endometrial niche cells cocultured with eMSCs contained increased levels of C-X-C motif ligand 1 (CXCL1), CXCL5 and interleukin 6. Immunohistochemical staining Conditioned media of endometrial niche cells cocultured with eMSCs contained increased levels of C-X-C motif ligand 1 (CXCL1), CXCL5 and interleukin 6. Western blot,Flow cytometry,Qrt-PCR,WNT reporter assay,Immunofluorescence CXCL5 Conditioned media of endometrial niche cells cocultured with eMSCs contained increased levels of C-X-C motif ligand 1 (CXCL1), CXCL5 and interleukin 6. 32555468 chr4 99273246 99275246 ADH1A Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues. human Nervous High+Lowthroughput Genetic variants associated with alcohol dependence co-ordinate regulation of ADH genes in gastrointestinal and adipose tissues 是 rs4699741,rs1229984,rs17028615,rs1789891,rs1789924,rs1826907,rs2066702 neuronal cell E_01_0613 LD analysis Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues. Immunohistochemical staining Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues. LD analysis ADH1A,ADH1B,ADH1C,ADH4 Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues.;Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues.;Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues.;Identifed eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues. 32566584 chr22 39516997 39518997 ATF4 Results: BC significantly inhibited AGE-induced cell death and apoptosis in H9c2 cells. BC had a suppressive effect on intracellular ROS production and antioxidative enzyme reduction. Moreover, BC decreased hyperactive endoplasmic reticulum (ER) stress and autophagy in H9c2 cells. Furthermore, BC exerted a cardioprotective effect in AGE-induced H9c2 cells via the activation of the PI3K/Akt/mTOR signaling pathway. human Musculature High+Lowthroughput Beta carotene protects H9c2 cardiomyocytes from advanced glycation end product-induced endoplasmic reticulum stress, apoptosis, and autophagy via the PI3K/Akt/mTOR signaling pathway 否 Diabetic cardiomyopathy H2c9 cell E_01_0614 flow cytometry，Western blotting，Enzyme-linked immunosorbent assay Results: BC significantly inhibited AGE-induced cell death and apoptosis in H9c2 cells. BC had a suppressive effect on intracellular ROS production and antioxidative enzyme reduction. Moreover, BC decreased hyperactive endoplasmic reticulum (ER) stress and autophagy in H9c2 cells. Furthermore, BC exerted a cardioprotective effect in AGE-induced H9c2 cells via the activation of the PI3K/Akt/mTOR signaling pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results: BC significantly inhibited AGE-induced cell death and apoptosis in H9c2 cells. BC had a suppressive effect on intracellular ROS production and antioxidative enzyme reduction. Moreover, BC decreased hyperactive endoplasmic reticulum (ER) stress and autophagy in H9c2 cells. Furthermore, BC exerted a cardioprotective effect in AGE-induced H9c2 cells via the activation of the PI3K/Akt/mTOR signaling pathway. Immunohistochemical staining Results: BC significantly inhibited AGE-induced cell death and apoptosis in H9c2 cells. BC had a suppressive effect on intracellular ROS production and antioxidative enzyme reduction. Moreover, BC decreased hyperactive endoplasmic reticulum (ER) stress and autophagy in H9c2 cells. Furthermore, BC exerted a cardioprotective effect in AGE-induced H9c2 cells via the activation of the PI3K/Akt/mTOR signaling pathway. flow cytometry，Western blotting，Enzyme-linked immunosorbent assay ATF4 Results: BC significantly inhibited AGE-induced cell death and apoptosis in H9c2 cells. BC had a suppressive effect on intracellular ROS production and antioxidative enzyme reduction. Moreover, BC decreased hyperactive endoplasmic reticulum (ER) stress and autophagy in H9c2 cells. Furthermore, BC exerted a cardioprotective effect in AGE-induced H9c2 cells via the activation of the PI3K/Akt/mTOR signaling pathway. 32568442 chr6 32575193 32577193 HLA-DRB1 Polymorphisms predisposing to down-regulation of HLA-DR facilitate the Th1-to-Th2 transition and promote HCC development, possibly via selecting the HCC-risk HBV mutations. human connective High+Lowthroughput The genetic polymorphism down-regulating HLA-DRB1 enhancer activity facilitates HBV persistence, evolution and hepatocarcinogenesis in the Chinese Han population 是 rs3135395,rs3135338,rs477515 Cancer HepG2 cell E_01_0615 Statistical Analysis Polymorphisms predisposing to down-regulation of HLA-DR facilitate the Th1-to-Th2 transition and promote HCC development, possibly via selecting the HCC-risk HBV mutations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Polymorphisms predisposing to down-regulation of HLA-DR facilitate the Th1-to-Th2 transition and promote HCC development, possibly via selecting the HCC-risk HBV mutations. Immunohistochemical staining Polymorphisms predisposing to down-regulation of HLA-DR facilitate the Th1-to-Th2 transition and promote HCC development, possibly via selecting the HCC-risk HBV mutations. Statistical Analysis HLA-DRB1 Polymorphisms predisposing to down-regulation of HLA-DR facilitate the Th1-to-Th2 transition and promote HCC development, possibly via selecting the HCC-risk HBV mutations. 32570918 chr7 16788652 16790652 AGR2 In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. human connective High+Lowthroughput ZEB1/miR-200c/AGR2: A New Regulatory Loop Modulating the Epithelial-Mesenchymal Transition in Lung Adenocarcinomas 否 Lung Adenocarcinomas Lung cancer cell E_01_0616 Western Blot,ChIP,Immunoprecipitation In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. Immunohistochemical staining In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. Western Blot,ChIP,Immunoprecipitation AGR2 In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. 32579929 chr3 149366738 149368738 TM4SF1 These eRNAs help with the formation of a specific ERa-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. human High+Lowthroughput Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor 否 E_01_0617 Real-time RT PCR,RNA tethering luciferase assay,3C assay,ChIP-qPCR ,ChIP-Seq, These eRNAs help with the formation of a specific ERa-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These eRNAs help with the formation of a specific ERa-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Immunohistochemical staining These eRNAs help with the formation of a specific ERa-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Real-time RT PCR,RNA tethering luciferase assay,3C assay,ChIP-qPCR ,ChIP-Seq, TM4SF1,EFEMP1 These eRNAs help with the formation of a specific ERa-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes.;These eRNAs help with the formation of a specific ERa-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. 32585424 chr1 161036785 161038785 USF1 All possible rearrangements include a head-to-head fusion between a completely duplicated PCSK9 and a chromosomal region, normally situated ~80 kb away, that includes HNF4 and USF1 binding sites that could promote transcription of the PCSK9 gene. human High+Lowthroughput Molecular mechanism linking a novel PCSK9 copy number variant to severe hypercholesterolemia 否 Premature atherosclerosis E_01_0618 Whole exome seq All possible rearrangements include a head-to-head fusion between a completely duplicated PCSK9 and a chromosomal region, normally situated ~80 kb away, that includes HNF4 and USF1 binding sites that could promote transcription of the PCSK9 gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq All possible rearrangements include a head-to-head fusion between a completely duplicated PCSK9 and a chromosomal region, normally situated ~80 kb away, that includes HNF4 and USF1 binding sites that could promote transcription of the PCSK9 gene. Immunohistochemical staining All possible rearrangements include a head-to-head fusion between a completely duplicated PCSK9 and a chromosomal region, normally situated ~80 kb away, that includes HNF4 and USF1 binding sites that could promote transcription of the PCSK9 gene. Whole exome seq PCSK9 USF1 All possible rearrangements include a head-to-head fusion between a completely duplicated PCSK9 and a chromosomal region, normally situated ~80 kb away, that includes HNF4 and USF1 binding sites that could promote transcription of the PCSK9 gene. All possible rearrangements include a head-to-head fusion between a completely duplicated PCSK9 and a chromosomal region, normally situated ~80 kb away, that includes HNF4 and USF1 binding sites that could promote transcription of the PCSK9 gene. 32586085 chr14 23627675 23629675 DHRS2 Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes. human High+Lowthroughput LEF1 Induces DHRS2 Gene Expression in Human Acute Leukemia Jurkat T-Cells 否 Human Acute T cell E_01_0619 siRNA Transfection,RNA Isolation,qRT-PCR,Western Blotting Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes. Immunohistochemical staining Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes. siRNA Transfection,RNA Isolation,qRT-PCR,Western Blotting DHRS2 LEF1 Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes. Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes. 32593213 chr7 16788696 16790696 AGR2 Our data showed that AGR2 upregulated both HIF-1α and HIF-2α expression in Caki-1 cells increasing the expression of HIF-activated genes (glucose transporter 1, phosphoglycerate kinase 1, vascular endothelial growth factor A, and transforming growth factor-alpha) under the hypoxic conditions. human High+Lowthroughput Anterior gradient 2 promotes tumorigenesis through upregulation of CCAAT-enhancer binding protein beta and hypoxia-inducible factor-2α and subsequent secretion of interleukin-6, interleukin-8, and vascular endothelial growth factor in the Caki-1 clear cell renal cell carcinoma cell line 否 Renal cell carcinoma Caki-1 cell E_01_0620 Rtq-PCR,Western blot,Enzyme-linked immunosorbent assays,Statistical analysis Our data showed that AGR2 upregulated both HIF-1α and HIF-2α expression in Caki-1 cells increasing the expression of HIF-activated genes (glucose transporter 1, phosphoglycerate kinase 1, vascular endothelial growth factor A, and transforming growth factor-alpha) under the hypoxic conditions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data showed that AGR2 upregulated both HIF-1α and HIF-2α expression in Caki-1 cells increasing the expression of HIF-activated genes (glucose transporter 1, phosphoglycerate kinase 1, vascular endothelial growth factor A, and transforming growth factor-alpha) under the hypoxic conditions. Immunohistochemical staining Our data showed that AGR2 upregulated both HIF-1α and HIF-2α expression in Caki-1 cells increasing the expression of HIF-activated genes (glucose transporter 1, phosphoglycerate kinase 1, vascular endothelial growth factor A, and transforming growth factor-alpha) under the hypoxic conditions. Rtq-PCR,Western blot,Enzyme-linked immunosorbent assays,Statistical analysis AGR2 Our data showed that AGR2 upregulated both HIF-1α and HIF-2α expression in Caki-1 cells increasing the expression of HIF-activated genes (glucose transporter 1, phosphoglycerate kinase 1, vascular endothelial growth factor A, and transforming growth factor-alpha) under the hypoxic conditions. 32600276 chr16 86507926 86509926 FOXF1 Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. human Epithelial High+Lowthroughput Genotype-phenotype correlation in two Polish neonates with alveolar capillary dysplasia 否 Alveolar capillary dysplasia epithelial cell E_01_0621 Sanger seq, Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. Immunohistochemical staining Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. Sanger seq, FOXF1 Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. 32606728 chr7 148804477 148806477 EZH2 Treatment with diosgenin alone caused a dose-dependent decrease in the cell viability, and combined treatment with an EZH2 inhibitor plus GSK126 caused a further significant decrease. human Epithelial High+Lowthroughput Diosgenin and GSK126 Produce Synergistic Effects on Epithelial-Mesenchymal Transition in Gastric Cancer Cells by Mediating EZH2 via the Rho/ROCK Signaling Pathway 否 Gastric cancer MGC-803 cell E_01_0622 RNA Extraction，Quantitative PCR，CCK-8 Assay，Flow Cytometry Analysis，Western Blot Treatment with diosgenin alone caused a dose-dependent decrease in the cell viability, and combined treatment with an EZH2 inhibitor plus GSK126 caused a further significant decrease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Treatment with diosgenin alone caused a dose-dependent decrease in the cell viability, and combined treatment with an EZH2 inhibitor plus GSK126 caused a further significant decrease. Immunohistochemical staining Treatment with diosgenin alone caused a dose-dependent decrease in the cell viability, and combined treatment with an EZH2 inhibitor plus GSK126 caused a further significant decrease. RNA Extraction，Quantitative PCR，CCK-8 Assay，Flow Cytometry Analysis，Western Blot EZH2 Treatment with diosgenin alone caused a dose-dependent decrease in the cell viability, and combined treatment with an EZH2 inhibitor plus GSK126 caused a further significant decrease. 32618141 chr7 18084226 18086226 HDAC9 Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2. human High+Lowthroughput DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure 否 Ischaemic cardiomyopathy E_01_0623 Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2. Immunohistochemical staining Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2. HDAC9,PDSS2 Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2.;Genes of particular interest as novel candidate markers of the heart failure phenotype with reduced methylation were HDAC9, JARID2, and GREM1 and with increased methylation PDSS2. 32626925 chr7 148804015 148806015 EZH2 In addition, enhancer of zeste homolog 2 (EZH2), a well-known oncogene, was proven to be a direct target of miR-144-3p, and its protein expression was negatively regulated by miR-144-3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR-144-3p level in OSCC tissues. human Epithelial High+Lowthroughput miR?144?3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the?downregulation of the oncogenic gene, EZH2 否 Oral squamous cell carcinoma HSC 2 cell E_01_0624 RT‑qPCR,Cell transfection,Luciferase assay,Western blot In addition, enhancer of zeste homolog 2 (EZH2), a well-known oncogene, was proven to be a direct target of miR-144-3p, and its protein expression was negatively regulated by miR-144-3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR-144-3p level in OSCC tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, enhancer of zeste homolog 2 (EZH2), a well-known oncogene, was proven to be a direct target of miR-144-3p, and its protein expression was negatively regulated by miR-144-3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR-144-3p level in OSCC tissues. Immunohistochemical staining In addition, enhancer of zeste homolog 2 (EZH2), a well-known oncogene, was proven to be a direct target of miR-144-3p, and its protein expression was negatively regulated by miR-144-3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR-144-3p level in OSCC tissues. RT‑qPCR,Cell transfection,Luciferase assay,Western blot EZH2 In addition, enhancer of zeste homolog 2 (EZH2), a well-known oncogene, was proven to be a direct target of miR-144-3p, and its protein expression was negatively regulated by miR-144-3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR-144-3p level in OSCC tissues. 30459414 chr1 156460934 156462934 MEF2D We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). human High+Lowthroughput A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts 是 rs200395694,rs867059436,rs576275580 Systemic lupus erythematosus T, B, NK cell E_01_0625 Gene array capture，Seq,Gene array capture We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). Immunohistochemical staining We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). Gene array capture，Seq,Gene array capture MEF2D We identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1 10). 30456215 chr11 65495184 65497184 MALAT1 MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. human High+Lowthroughput Transcriptional Profiling of Hypoxia-Regulated Non-coding RNAs in Human Primary Endothelial Cells 否 Human atherosclerotic lesions Primary endothelial cell E_01_0626 GRO-Seq and RNA-Seq, MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. Immunohistochemical staining MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. GRO-Seq and RNA-Seq, MALAT1 MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. 30455249 chr8 101489305 101491305 GRHL2 pS118-ER occupied a subset of ER binding sites which were associated with the active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. human High+Lowthroughput The Phosphorylated Estrogen Receptor α (ER) Cistrome Identifies a Subset of Active Enhancers Enriched for Direct ER-DNA Binding and the Transcription Factor GRHL2 否 Other MCF-7 cell E_01_0627 Western Blot，Transfection，Chromatin Immunoprecipitation，Specificity and Affinity for Proteins (SNAP) Array,ChIP-seq pS118-ER occupied a subset of ER binding sites which were associated with the active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq pS118-ER occupied a subset of ER binding sites which were associated with the active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. Immunohistochemical staining pS118-ER occupied a subset of ER binding sites which were associated with the active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. Western Blot，Transfection，Chromatin Immunoprecipitation，Specificity and Affinity for Proteins (SNAP) Array,ChIP-seq GRHL2 pS118-ER occupied a subset of ER binding sites which were associated with the active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. 30453884 chr15 78562655 78564655 CHRNA5 rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. human peripheral High+Lowthroughput Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence 是 rs16969968,rs880395,rs1948,rs4887074 Nicotine dependence and other smoking related disorders E_01_0628 Logistic regression，Multivariate regression rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. Immunohistochemical staining rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. Logistic regression，Multivariate regression CHRNA5 rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. 30451839 chr2 60447405 60449405 BCL11A At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable. human High+Lowthroughput Orthogonal Cas9-Cas9 chimeras provide a versatile platform for genome editing 否 Other Embryonic kidney cells E_01_0629 transfection/electroporation,GFP-reporter assay,Immunofluorescence,Western blot,deep sequencing,GUIDE-seq off-target analysis At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable. Immunohistochemical staining At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable. transfection/electroporation,GFP-reporter assay,Immunofluorescence,Western blot,deep sequencing,GUIDE-seq off-target analysis BCL11A At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable. 30450701 chr1 26174578 26176578 CNKSR1 CNKSR1 gene defect can cause syndromic autosomal recessiveintellectual disability human High+Lowthroughput CNKSR1 gene defect can cause syndromic autosomal recessive intellectual disability 是 rs10916983,rs849961 Syndromic autosomal recessive intellectual disability Lymphoblast E_01_0630 Protein extraction，Western blot analysis，Quantitative RT–PCR analysis of RNAi knockdown，Immunostaining CNKSR1 gene defect can cause syndromic autosomal recessiveintellectual disability Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CNKSR1 gene defect can cause syndromic autosomal recessiveintellectual disability Immunohistochemical staining CNKSR1 gene defect can cause syndromic autosomal recessiveintellectual disability Protein extraction，Western blot analysis，Quantitative RT–PCR analysis of RNAi knockdown，Immunostaining CNKSR1 CNKSR1 gene defect can cause syndromic autosomal recessiveintellectual disability 30448425 chr17 42310893 42312893 STAT3 HSP90 inhibitor ganetespib blocks pro-inflammatory responses in heat shock treated N9 cells via a signalling mechanism involving HSP90β and STAT3. human High+Lowthroughput Inhibition of HSP90β by ganetespib blocks the microglial signalling of evoked pro-inflammatory responses to heat shock 否 Heat shock microglial cell E_01_0631 Cell viability assay,ELISA,Flow Cytometry,Quantitative real-time polymerase chain reaction,Western blot,siRNA transfection,Immunofluorescence HSP90 inhibitor ganetespib blocks pro-inflammatory responses in heat shock treated N9 cells via a signalling mechanism involving HSP90β and STAT3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HSP90 inhibitor ganetespib blocks pro-inflammatory responses in heat shock treated N9 cells via a signalling mechanism involving HSP90β and STAT3. Immunohistochemical staining HSP90 inhibitor ganetespib blocks pro-inflammatory responses in heat shock treated N9 cells via a signalling mechanism involving HSP90β and STAT3. Cell viability assay,ELISA,Flow Cytometry,Quantitative real-time polymerase chain reaction,Western blot,siRNA transfection,Immunofluorescence STAT3 HSP90 inhibitor ganetespib blocks pro-inflammatory responses in heat shock treated N9 cells via a signalling mechanism involving HSP90β and STAT3. 30446688 chr4 190171332 190173332 DUX4 Anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5. human High+Lowthroughput Low level DUX4 expression disrupts myogenesis through deregulation of myogenic gene expression 否 Facioscapulohumeral muscular dystrophy myoblast cell E_01_0632 Annexin V/7-AAD staining,Luciferase assay,RT-qPCR,immunostaining,western blots Anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5. Immunohistochemical staining Anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5. Annexin V/7-AAD staining,Luciferase assay,RT-qPCR,immunostaining,western blots DUX4L1,MYF5 Anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5. ;Anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5. 30446587 chr4 108044811 108046811 LEF1 Niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing CRC to chemoradiation. human High+Lowthroughput Inhibition of LEF1-Mediated DCLK1 by Niclosamide Attenuates Colorectal Cancer Stemness 否 colorectal cancer E_01_0633 Luciferase reporter assay, Western blot,immunofluorescence analysis,histopathological analysis ,short tandem repeat profiling analysis, cell proliferation assay, MTT assay,FACS analysis Niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing CRC to chemoradiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing CRC to chemoradiation. Immunohistochemical staining Niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing CRC to chemoradiation. Luciferase reporter assay, Western blot,immunofluorescence analysis,histopathological analysis ,short tandem repeat profiling analysis, cell proliferation assay, MTT assay,FACS analysis LEF1 Niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing CRC to chemoradiation. 30430607 chr19 33297457 33299457 CEBPA Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. human High+Lowthroughput Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers 否 prostatic cancer tumor cell E_01_0634 Immunohistochemistry, Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. Immunohistochemical staining Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. Immunohistochemistry, CEBPA,ERG,TMPRSS2,PTEN Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers.;Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers.;Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers.;Loss of CCAAT-enhancer-binding protein alpha (CEBPA) is linked to poor prognosis in PTEN deleted and TMPRSS2:ERG fusion type prostate cancers. 30428538 chr11 75397365 75399365 RPS3 The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. human High+Lowthroughput Hsp90 Interacts with the Bacterial Effector NleH1 否 Other B cell E_01_0635 Protein purification,Cell culture and transfection,Co-immunoprecipitation assay,Mass Spectrometry,RNA interference and transfection, The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. Immunohistochemical staining The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. Protein purification,Cell culture and transfection,Co-immunoprecipitation assay,Mass Spectrometry,RNA interference and transfection, RPS3 The EHEC NleH1 effector inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reducing the nuclear translocation of the ribosomal protein S3 (RPS3). NleH1 prevents RPS3 phosphorylation by the IκB kinase-β (IKKβ). IKKβ is a central kinase in the NF-κB pathway, yet NleH1 only restricts the phosphorylation of a subset of the IKKβ substrates. We hypothesized that a protein cofactor might dictate this inhibitory specificity. 30429326 chr19 16321911 16323911 KLF2 H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs),CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. human High+Lowthroughput Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics，ChIP-PCR，luciferase assays 是 Coronary artery disease and ischemic stroke aortic endothelial cell E_01_0636 ATAC-Seq，Genome-wide association studies (GWAS)，ChIP-seq， H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs),CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs),CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. Immunohistochemical staining H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs),CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. ATAC-Seq，Genome-wide association studies (GWAS)，ChIP-seq， KLF2 H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs),CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. 30428345 chr3 189628920 189630920 TP63 The transcription factor TP63 (DNp63) is sufficient to install and sustain the enhancer landscape and transcriptional signature of the squamous lineage in human PDA cells. We also demonstrate that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes, including enhanced cell motility and invasion, and an accelerated growth of primary PDA tumors and metastases in vivo. human High+Lowthroughput TP63-Mediated Enhancer Reprogramming Drives the Squamous Subtype of Pancreatic Ductal Adenocarcinoma 是 Squamous subtype E_01_0637 Plasmid Construction，Lentiviral Production and Infection，In Vitro Phenotypic Assays，CRISPR-Based Targeting，shRNA targeting in BxPC3 cells and hF3 organoids，In Vivo Transplantation Experiments，Histology and Immunohistochemistry，Cell Lysate Preparation for Western Blot Analysis，RNA Extraction and RT-PCR，RNA-seq Library Construction，ChIP and ChIP-Seq Library Construction，RNA-Seq Data Analysis，ChIP-Seq Analysis The transcription factor TP63 (DNp63) is sufficient to install and sustain the enhancer landscape and transcriptional signature of the squamous lineage in human PDA cells. We also demonstrate that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes, including enhanced cell motility and invasion, and an accelerated growth of primary PDA tumors and metastases in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcription factor TP63 (DNp63) is sufficient to install and sustain the enhancer landscape and transcriptional signature of the squamous lineage in human PDA cells. We also demonstrate that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes, including enhanced cell motility and invasion, and an accelerated growth of primary PDA tumors and metastases in vivo. Immunohistochemical staining The transcription factor TP63 (DNp63) is sufficient to install and sustain the enhancer landscape and transcriptional signature of the squamous lineage in human PDA cells. We also demonstrate that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes, including enhanced cell motility and invasion, and an accelerated growth of primary PDA tumors and metastases in vivo. Plasmid Construction，Lentiviral Production and Infection，In Vitro Phenotypic Assays，CRISPR-Based Targeting，shRNA targeting in BxPC3 cells and hF3 organoids，In Vivo Transplantation Experiments，Histology and Immunohistochemistry，Cell Lysate Preparation for Western Blot Analysis，RNA Extraction and RT-PCR，RNA-seq Library Construction，ChIP and ChIP-Seq Library Construction，RNA-Seq Data Analysis，ChIP-Seq Analysis TP63 The transcription factor TP63 (DNp63) is sufficient to install and sustain the enhancer landscape and transcriptional signature of the squamous lineage in human PDA cells. We also demonstrate that TP63-driven enhancer reprogramming promotes aggressive tumor phenotypes, including enhanced cell motility and invasion, and an accelerated growth of primary PDA tumors and metastases in vivo. 30422892 chr10 102741141 102743141 WBP1L The intronic SNP rs176185, which may influence promoter histone, enhancer histone, DNase and regulatory motifs and showed ciseQTL effect on WBP1L, was associated with hypertension in the Chinese Han population (P = 0.0119). human High+Lowthroughput Detection of Putative Functional Single Nucleotide Polymorphisms in Blood Pressure Loci and Validation of Association Between Single Nucleotide Polymorphism in WBP1L and Hypertension in the Chinese Han Population 否 rs176185 Hypertension, coronary artery disease, or ischemic stroke leukocyte E_01_0638 DNA Extraction，SNP Genotyping The intronic SNP rs176185, which may influence promoter histone, enhancer histone, DNase and regulatory motifs and showed ciseQTL effect on WBP1L, was associated with hypertension in the Chinese Han population (P = 0.0119). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The intronic SNP rs176185, which may influence promoter histone, enhancer histone, DNase and regulatory motifs and showed ciseQTL effect on WBP1L, was associated with hypertension in the Chinese Han population (P = 0.0119). Immunohistochemical staining The intronic SNP rs176185, which may influence promoter histone, enhancer histone, DNase and regulatory motifs and showed ciseQTL effect on WBP1L, was associated with hypertension in the Chinese Han population (P = 0.0119). DNA Extraction，SNP Genotyping WBP1L The intronic SNP rs176185, which may influence promoter histone, enhancer histone, DNase and regulatory motifs and showed ciseQTL effect on WBP1L, was associated with hypertension in the Chinese Han population (P = 0.0119). 30419347 chr15 61854218 61856218 Myc Myc plays a key role in aggressive proliferation-related phenotypes exhibited by breast cancer cells expressing ERα mutations. mouse High+Lowthroughput Estrogen-independent Myc overexpression confers endocrine therapy resistance on breast cancer cells expressing ERαY537S and ERαD538G mutations 否 Metastatic breast cancer T47D and MCF7 cells E_01_0639 3 qRT-PCR,Western blot,siRNA knockdowns, Chromatin immunoprecipitation (ChIP),Lentivirus infection,Cell invasion assay,RNAseq Myc plays a key role in aggressive proliferation-related phenotypes exhibited by breast cancer cells expressing ERα mutations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Myc plays a key role in aggressive proliferation-related phenotypes exhibited by breast cancer cells expressing ERα mutations. Immunohistochemical staining Myc plays a key role in aggressive proliferation-related phenotypes exhibited by breast cancer cells expressing ERα mutations. 3 qRT-PCR,Western blot,siRNA knockdowns, Chromatin immunoprecipitation (ChIP),Lentivirus infection,Cell invasion assay,RNAseq Myc Myc plays a key role in aggressive proliferation-related phenotypes exhibited by breast cancer cells expressing ERα mutations. 30417100 chr4 105143331 105145331 TET2 TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. human High+Lowthroughput TET2 coactivates gene expression through demethylation of enhancers 否 cancer MCF7 cell E_01_0640 RNA-seq analysis,ChIP-seq analysis, Western blot TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. Immunohistochemical staining TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. RNA-seq analysis,ChIP-seq analysis, Western blot TET2 TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. 30411085 chr4 108044928 108046928 LEF1 LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. human High+Lowthroughput Lymphoid Enhancer Factor 1 Contributes to Hepatocellular Carcinoma Progression Through Transcriptional Regulation of Epithelial-Mesenchymal Transition Regulators and Stemness Genes 否 Hepatocellular carcinoma HCC cell lines E_01_0641 ChIP-seq,IHC staining,western blot,colony formation assay, and invasion assay,Luc assay,cloning of gene promoter regions,site-directed mutagenesis,transient transfections LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. Immunohistochemical staining LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. ChIP-seq,IHC staining,western blot,colony formation assay, and invasion assay,Luc assay,cloning of gene promoter regions,site-directed mutagenesis,transient transfections LEF1 LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. LEF1 plays a pivotal role in HCC progression through transcriptional regulation of Oct4 and EMT regulators. 31097419 chr6 31572783 31574783 TNF Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strateg human High+Lowthroughput TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcriptomic and epigenomic analysis 否 inflammation macrophage E_01_0642 chiP-seq ，aTac-seq ，RNAseq ，RT-qPCR ，bioinformatics analysis ， statistical analysis Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strateg Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strateg Immunohistochemical staining Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strateg chiP-seq ，aTac-seq ，RNAseq ，RT-qPCR ，bioinformatics analysis ， statistical analysis TNF Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strateg 31026067 chr11 1992169 1994169 H19 Cytidine cytidine adenosine adenosine thymidine (CCAAT) enhancer binding protein α (CEBP α) and peroxisome proliferator activated receptor γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation.The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation.miR 30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation human High+Lowthroughput PIK3CD induces cell growth and invasion by activating AKT/GSK-3β/β-catenin signaling in colorectal cancer 否 Obesity related disorders mesenchymal stem cell E_01_0643 Cell transfection ，Immunoblotting ，Real‐time PCR ，RIP ，Luciferase reporter assay Cytidine cytidine adenosine adenosine thymidine (CCAAT) enhancer binding protein α (CEBP α) and peroxisome proliferator activated receptor γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation.The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation.miR 30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Cytidine cytidine adenosine adenosine thymidine (CCAAT) enhancer binding protein α (CEBP α) and peroxisome proliferator activated receptor γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation.The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation.miR 30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation Immunohistochemical staining Cytidine cytidine adenosine adenosine thymidine (CCAAT) enhancer binding protein α (CEBP α) and peroxisome proliferator activated receptor γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation.The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation.miR 30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation Cell transfection ，Immunoblotting ，Real‐time PCR ，RIP ，Luciferase reporter assay H19 Cytidine cytidine adenosine adenosine thymidine (CCAAT) enhancer binding protein α (CEBP α) and peroxisome proliferator activated receptor γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation.The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation.miR 30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation 30865855 chr14 21495515 21497515 METTL3 The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. human High+Lowthroughput METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPb pathway via an m6A-YTHDF2–dependent manner 否 Obesity Bone marrow stem cell E_01_0644 flow cytometry ，Real-time quantitative PCR ， staining ，Protein extraction ，Western blot ，Cell transfection ，Immunofluorescence assay ，Quantitative analysis ，Chromatin immunoprecipitation assay ，Luciferase reporter assay The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. Immunohistochemical staining The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. flow cytometry ，Real-time quantitative PCR ， staining ，Protein extraction ，Western blot ，Cell transfection ，Immunofluorescence assay ，Quantitative analysis ，Chromatin immunoprecipitation assay ，Luciferase reporter assay METTL3 The deletion of m6A writer protein methyltransferaselike (METTL)3 in porcine BMSCs (pBMSCs) could promote adipogenesis and janus kinase (JAK)1 protein expressionvia anm6 A-dependent way. Knockdown ofMETTL3 decreasedmRNAm6 A levels of JAK1, leading to enhanced YTH m6 A RNA binding protein 2 (YTHDF2)-dependent JAK1 mRNA stability. We further demonstrated that JAK1 activated signal transducer and activator of transcription (STAT) 5 through regulation of its phosphorylation to bind to the promoter of CCAAT/enhancer binding protein (C/EBP) b, which could ultimately lead to a modulated adipogenic process. 30826407 chr2 226728494 226730494 IRS1 Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). human High+Lowthroughput A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium 否 Type 2 diabetes mellitus HeLa cell E_01_0645 Nuclear magnetic resonance (NMR) spectroscopy analysis ，RNA extraction and real-time PCR ，Western blot analysis ，Histopathological analysis ,Analysis of glycated hemoglobin and β-cell function Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Immunohistochemical staining Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). Nuclear magnetic resonance (NMR) spectroscopy analysis ，RNA extraction and real-time PCR ，Western blot analysis ，Histopathological analysis ,Analysis of glycated hemoglobin and β-cell function IRS1 Phosphatidylinositol-3-kinase (PI3K), 74 insulin receptor substrate 1 (IRS1), and glucose transporter 4 (GLUT4) play crucial roles in 75 glucose metabolism and insulin resistance. The mechanism begins with the stimulation of 76 insulin receptor intrinsic kinase activity to activate PI3K signaling. Then, PI3K inhibits the 77 c-Jun N-terminal kinase 1 (JNK1) activity in succession. Moreover, GLUT4, which is 78 regulated by insulin, is able to reduce glucose levels through participating in the IRS/PI3K 79 signaling pathway (Chen et al., 2018). 30402268 chr1 247413739 247415739 NLRP3 Functional experiments in the HA20 patients immune cells uncovered a novel caspase-8-dependent mechanism of NLRP3 inflammasome hyperresponsiveness that mediated the excessive secretion of interleukin-1β and interleukin-18. human High+Lowthroughput Haploinsufficiency of A20 impairs protein-protein interactome and leads into caspase-8-dependent enhancement of NLRP3 inflammasome activation 否 Inflammatory and autoimmune diseases E_01_0646 Luciferase assay,Affinity purification and mass spectrometry,Culture and stimulation of peripheral blood mononuclear cells (PBMCs),Quantitative real-time PCR Functional experiments in the HA20 patients immune cells uncovered a novel caspase-8-dependent mechanism of NLRP3 inflammasome hyperresponsiveness that mediated the excessive secretion of interleukin-1β and interleukin-18. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional experiments in the HA20 patients immune cells uncovered a novel caspase-8-dependent mechanism of NLRP3 inflammasome hyperresponsiveness that mediated the excessive secretion of interleukin-1β and interleukin-18. Immunohistochemical staining Functional experiments in the HA20 patients immune cells uncovered a novel caspase-8-dependent mechanism of NLRP3 inflammasome hyperresponsiveness that mediated the excessive secretion of interleukin-1β and interleukin-18. Luciferase assay,Affinity purification and mass spectrometry,Culture and stimulation of peripheral blood mononuclear cells (PBMCs),Quantitative real-time PCR NLRP3 Functional experiments in the HA20 patients immune cells uncovered a novel caspase-8-dependent mechanism of NLRP3 inflammasome hyperresponsiveness that mediated the excessive secretion of interleukin-1β and interleukin-18. 30387181 chr12 2854445 2856445 FOXM1 Downregulation of miR 134 attenuated DADS induced antitumor capacity. Further bioinformatics prediction analysis revealed that the 3 untranslated region (3 UTR) of Forkhead Box M1 (FOXM1) harbored miR 134 binding sites, and overexpression of miR 134 repressed the luciferase activity of the reporting vector containing FOXM1 3 UTR. human High+Lowthroughput Diallyl disulfide suppresses FOXM1-mediated proliferation and invasion in osteosarcoma by upregulating miR-134 否 Osteosarcoma U2OS and MG-63 E_01_0647 cell transfection,Quantitative real‐time polymerase Dual‐luciferase reporter assay,Western blo,chain reaction,Cell viability assay,Cell colony formation assay,Cell invasion assay Downregulation of miR 134 attenuated DADS induced antitumor capacity. Further bioinformatics prediction analysis revealed that the 3 untranslated region (3 UTR) of Forkhead Box M1 (FOXM1) harbored miR 134 binding sites, and overexpression of miR 134 repressed the luciferase activity of the reporting vector containing FOXM1 3 UTR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Downregulation of miR 134 attenuated DADS induced antitumor capacity. Further bioinformatics prediction analysis revealed that the 3 untranslated region (3 UTR) of Forkhead Box M1 (FOXM1) harbored miR 134 binding sites, and overexpression of miR 134 repressed the luciferase activity of the reporting vector containing FOXM1 3 UTR. Immunohistochemical staining Downregulation of miR 134 attenuated DADS induced antitumor capacity. Further bioinformatics prediction analysis revealed that the 3 untranslated region (3 UTR) of Forkhead Box M1 (FOXM1) harbored miR 134 binding sites, and overexpression of miR 134 repressed the luciferase activity of the reporting vector containing FOXM1 3 UTR. cell transfection,Quantitative real‐time polymerase Dual‐luciferase reporter assay,Western blo,chain reaction,Cell viability assay,Cell colony formation assay,Cell invasion assay FOXM1 Downregulation of miR 134 attenuated DADS induced antitumor capacity. Further bioinformatics prediction analysis revealed that the 3 untranslated region (3 UTR) of Forkhead Box M1 (FOXM1) harbored miR 134 binding sites, and overexpression of miR 134 repressed the luciferase activity of the reporting vector containing FOXM1 3 UTR. 30383449 chr19 10651482 10653482 ILF3 Together these data suggest that in endothelial cells, the RNA stability protein, ILF3, plays a novel and central role in angiogenesis. human High+Lowthroughput RNA stability protein ILF3 mediates cytokine-induced angiogenesis 否 Cardiac ischemia, neurodegeneration, respiratory distress, tissue hypoxia E_01_0648 Immunohistochemistry and immunocytochemistry，Small interfering RNA knockdown，Western blot，Migration assay，Proliferation assay，Apoptosis assay，Quantitative RT-PCR，RNA immunoprecipitation Together these data suggest that in endothelial cells, the RNA stability protein, ILF3, plays a novel and central role in angiogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Together these data suggest that in endothelial cells, the RNA stability protein, ILF3, plays a novel and central role in angiogenesis. Immunohistochemical staining Together these data suggest that in endothelial cells, the RNA stability protein, ILF3, plays a novel and central role in angiogenesis. Immunohistochemistry and immunocytochemistry，Small interfering RNA knockdown，Western blot，Migration assay，Proliferation assay，Apoptosis assay，Quantitative RT-PCR，RNA immunoprecipitation ILF3 Together these data suggest that in endothelial cells, the RNA stability protein, ILF3, plays a novel and central role in angiogenesis. 30376989 chr1 29144924 29146924 SRSF4 Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. human High+Lowthroughput Binding of SRSF4 to a novel enhancer modulates splicing of exon 6 of Fas pre-mRNA 否 Other HCT116 cell E_01_0649 Viral infection，RT-PCR，Immunoblotting，RNA binding assay，Electrophoretic Mobility Shift Assay (EMSA) Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. Immunohistochemical staining Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. Viral infection，RT-PCR，Immunoblotting，RNA binding assay，Electrophoretic Mobility Shift Assay (EMSA) SRSF4 Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. 30376817 chr5 88713851 88715851 MEF2C MEF2C mutations are associated with a broad clinical spectrum, ranged from classical RTT to non-syndromic ID. Through our study, it can be inferred that there is correlation between the phenotype and MEF2C-genotype, the mutation site. Overall, the MEF2C gene mutational analysis should be performed in ID cohort, especially in patients with features overlapped with RTT human High+Lowthroughput Novel MEF2C point mutations in Chinese patients with Rett (-like) syndrome or non-syndromic intellectual disability: insights into genotype-phenotype correlation 否 Rett (− like) syndrome or nonsyndromic intellectual disability in China E_01_0650 Seq MEF2C mutations are associated with a broad clinical spectrum, ranged from classical RTT to non-syndromic ID. Through our study, it can be inferred that there is correlation between the phenotype and MEF2C-genotype, the mutation site. Overall, the MEF2C gene mutational analysis should be performed in ID cohort, especially in patients with features overlapped with RTT Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2C mutations are associated with a broad clinical spectrum, ranged from classical RTT to non-syndromic ID. Through our study, it can be inferred that there is correlation between the phenotype and MEF2C-genotype, the mutation site. Overall, the MEF2C gene mutational analysis should be performed in ID cohort, especially in patients with features overlapped with RTT Immunohistochemical staining MEF2C mutations are associated with a broad clinical spectrum, ranged from classical RTT to non-syndromic ID. Through our study, it can be inferred that there is correlation between the phenotype and MEF2C-genotype, the mutation site. Overall, the MEF2C gene mutational analysis should be performed in ID cohort, especially in patients with features overlapped with RTT Seq MEF2C MEF2C mutations are associated with a broad clinical spectrum, ranged from classical RTT to non-syndromic ID. Through our study, it can be inferred that there is correlation between the phenotype and MEF2C-genotype, the mutation site. Overall, the MEF2C gene mutational analysis should be performed in ID cohort, especially in patients with features overlapped with RTT 30372441 chr7 19018038 19020038 TWIST1 Accordingly, haploinsufficiency of TWIST1 can cause limb and craniofacial malformations as part of Saethre-Chotzen syndrome. human High+Lowthroughput Unraveling the transcriptional regulation of TWIST1 in limb development 否 Saethri - chotzen syndrome HEK293T E_01_0651 ChIP-seq，ChIP-qPCR，4c-seq，Whole-mount in situ hybridization Accordingly, haploinsufficiency of TWIST1 can cause limb and craniofacial malformations as part of Saethre-Chotzen syndrome. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Accordingly, haploinsufficiency of TWIST1 can cause limb and craniofacial malformations as part of Saethre-Chotzen syndrome. Immunohistochemical staining Accordingly, haploinsufficiency of TWIST1 can cause limb and craniofacial malformations as part of Saethre-Chotzen syndrome. ChIP-seq，ChIP-qPCR，4c-seq，Whole-mount in situ hybridization TWIST1 Accordingly, haploinsufficiency of TWIST1 can cause limb and craniofacial malformations as part of Saethre-Chotzen syndrome. 30368870 chr7 148804504 148806504 EZH2 These findings indicated that ANCR upregulates EZH2 expression and physically binds to EZH2 in LF MSCs to suppress chondrogenic differentiation and calcification. Therefore, downregulated ANCR contributes to increasing of chondrocyte like cells and calcium deposition in CLF. ANCR may serve as a therapeutic target for CLF. human High+Lowthroughput Downregulation of antidifferentiation noncoding RNA promotes chondrogenic differentiation and calcification of ligamentum flavum-derived mesenchymal stem cells 否 Calcification of the ligamentum flavum (CLF) mesenchymal stem cell E_01_0652 These findings indicated that ANCR upregulates EZH2 expression and physically binds to EZH2 in LF MSCs to suppress chondrogenic differentiation and calcification. Therefore, downregulated ANCR contributes to increasing of chondrocyte like cells and calcium deposition in CLF. ANCR may serve as a therapeutic target for CLF. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings indicated that ANCR upregulates EZH2 expression and physically binds to EZH2 in LF MSCs to suppress chondrogenic differentiation and calcification. Therefore, downregulated ANCR contributes to increasing of chondrocyte like cells and calcium deposition in CLF. ANCR may serve as a therapeutic target for CLF. Immunohistochemical staining These findings indicated that ANCR upregulates EZH2 expression and physically binds to EZH2 in LF MSCs to suppress chondrogenic differentiation and calcification. Therefore, downregulated ANCR contributes to increasing of chondrocyte like cells and calcium deposition in CLF. ANCR may serve as a therapeutic target for CLF. EZH2 These findings indicated that ANCR upregulates EZH2 expression and physically binds to EZH2 in LF MSCs to suppress chondrogenic differentiation and calcification. Therefore, downregulated ANCR contributes to increasing of chondrocyte like cells and calcium deposition in CLF. ANCR may serve as a therapeutic target for CLF. 30366903 chr3 133743131 133745131 TF Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. human High+Lowthroughput Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development 否 Other embryonic cell E_01_0653 RNA-seq, ATAC-seq, ChIP-seq Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Immunohistochemical staining Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. RNA-seq, ATAC-seq, ChIP-seq TF CDX2 Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. 30365933 chr9 21138792 21140792 Keap1 Thus, the , -unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression. mouse High+Lowthroughput Shogaol but not gingerol has a neuroprotective effect on hemorrhagic brain injury: Contribution of the α, β-unsaturated carbonyl to heme oxygenase-1 expression 否 Hemorrhagic brain injury microglial cell E_01_0654 LDH release assay, Luciferase assay,Quantitative real-time RT-PCR,Western blot, Immunohistochemical staining, Thus, the , -unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, the , -unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression. Immunohistochemical staining Thus, the , -unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression. LDH release assay, Luciferase assay,Quantitative real-time RT-PCR,Western blot, Immunohistochemical staining, Keap1 Thus, the , -unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression. 30361341 chr8 127732519 127734519 MYC Genome-wide correlation of gene expression and chromatin accessibility predicts tens of thousands of putative interactions between distal regulatory elements and gene promoters, including key oncogenes and targets in cancer immunotherapy, such as MYC, SRC, BCL2, and PDL1. human High+Lowthroughput The chromatin accessibility landscape of primary human cancers 否 Primary human cancers cancer cell E_01_0655 ATAC-seq,HiChIP, immune infiltration analysis Genome-wide correlation of gene expression and chromatin accessibility predicts tens of thousands of putative interactions between distal regulatory elements and gene promoters, including key oncogenes and targets in cancer immunotherapy, such as MYC, SRC, BCL2, and PDL1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genome-wide correlation of gene expression and chromatin accessibility predicts tens of thousands of putative interactions between distal regulatory elements and gene promoters, including key oncogenes and targets in cancer immunotherapy, such as MYC, SRC, BCL2, and PDL1. Immunohistochemical staining Genome-wide correlation of gene expression and chromatin accessibility predicts tens of thousands of putative interactions between distal regulatory elements and gene promoters, including key oncogenes and targets in cancer immunotherapy, such as MYC, SRC, BCL2, and PDL1. ATAC-seq,HiChIP, immune infiltration analysis MYC Genome-wide correlation of gene expression and chromatin accessibility predicts tens of thousands of putative interactions between distal regulatory elements and gene promoters, including key oncogenes and targets in cancer immunotherapy, such as MYC, SRC, BCL2, and PDL1. 30361093 chr14 81469015 81471015 SEL1L Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD. human High+Lowthroughput Ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) prevents cell death in a cellular model of Parkinson's disease 否 Parkinson's disease SH-SY5Y human neuroblastoma cells E_01_0656 MTT assay,RNA interference,RNA isolation,quantitative real-time PCR,. Western blot Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD. Immunohistochemical staining Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD. MTT assay,RNA interference,RNA isolation,quantitative real-time PCR,. Western blot SEL1L Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD. 30359362 chr14 100235907 100237907 YY1 Our data therefore reveal a key role for CTCF-YY1 dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis. human High+Lowthroughput Disruption of CTCF-YY1-dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription 否 Human papillomas E_01_0657 ChIP,Chromatin immunoprecipitation,Western blot,RNA-Seq,FAIRE,qRT-PCR,3C Our data therefore reveal a key role for CTCF-YY1 dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data therefore reveal a key role for CTCF-YY1 dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis. Immunohistochemical staining Our data therefore reveal a key role for CTCF-YY1 dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis. ChIP,Chromatin immunoprecipitation,Western blot,RNA-Seq,FAIRE,qRT-PCR,3C YY1,CTCF Our data therefore reveal a key role for CTCF-YY1 dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis. ;Our data therefore reveal a key role for CTCF-YY1 dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis. 30358439 chrX 72326686 72328686 HDAC8 These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases human lung High+Lowthroughput HDAC8 inhibition ameliorates pulmonary fibrosis 否 Idiopathic pulmonary fibrosis (IPF) normal human lung fibroblasts E_01_0658 RNA interference，Immunoblots，Immunoprecipitation，Immunofluorescent staining，Type I collagen gel contraction assay ，qRT-PCR，ChIP-qPCR These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases Immunohistochemical staining These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases RNA interference，Immunoblots，Immunoprecipitation，Immunofluorescent staining，Type I collagen gel contraction assay ，qRT-PCR，ChIP-qPCR HDAC8 These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases 30357366 chr1 6783119 6785119 CAMTA1 Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease. human High+Lowthroughput TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease 否 Amyotrophic lateral sclerosis and frontotemporal dementia Motor neuron like cells E_01_0659 TRAP immunoprecipitations,RNA extraction, qRT-PCR,Crosslink immunoprecipitation (CLIP),Immunostaining,Reporter transfection, dual luciferase assays, knockdown Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease. Immunohistochemical staining Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease. TRAP immunoprecipitations,RNA extraction, qRT-PCR,Crosslink immunoprecipitation (CLIP),Immunostaining,Reporter transfection, dual luciferase assays, knockdown CAMTA1,DENND4A Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease. ;Our data reveal that TDP-43 can function as an mRNA-specific translational enhancer. Moreover, since CAMTA1 and DENND4A are linked to neurodegeneration, they suggest that this function could contribute to disease. 30356873 chr11 27652426 27654426 BDNF These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling human High+Lowthroughput Loss of Microglia and Impaired Brain-Neurotrophic Factor Signaling Pathway in a Comorbid Model of Chronic Pain and Depression 否 Major depressive disorder (MDD) and chronic pain microglial cell E_01_0660 Quantitative RT-PCR,Open Field Test (OFT),Tail Suspension Test (TST),Forced Swimming Test (FST),Immunohistochemistry,Western Blot,Visceromotor Response (VMR) These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling Immunohistochemical staining These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling Quantitative RT-PCR,Open Field Test (OFT),Tail Suspension Test (TST),Forced Swimming Test (FST),Immunohistochemistry,Western Blot,Visceromotor Response (VMR) BDNF These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling 30354296 chr8 58487490 58489490 CYP7A1 Two interacting regulatory SNPs modulate CYP7A1 expression and are associated with risk of coronary artery disease and diabetes mellitus. human High+Lowthroughput Interactions Between Regulatory Variants in CYP7A1 (Cholesterol 7α-Hydroxylase) Promoter and Enhancer Regions Regulate CYP7A1 Expression 是 rs3808607,rs9297994,rs2081687,rs983812,rs8192870,rs9297994 Coronary artery disease and diabetes Hepatocellular carcinoma cells E_01_0661 4C assay,chromatin immunoprecipitation qPCR assay,eporter gene assays ,CRISPR -mediated genome editing Two interacting regulatory SNPs modulate CYP7A1 expression and are associated with risk of coronary artery disease and diabetes mellitus. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Two interacting regulatory SNPs modulate CYP7A1 expression and are associated with risk of coronary artery disease and diabetes mellitus. Immunohistochemical staining Two interacting regulatory SNPs modulate CYP7A1 expression and are associated with risk of coronary artery disease and diabetes mellitus. 4C assay,chromatin immunoprecipitation qPCR assay,eporter gene assays ,CRISPR -mediated genome editing CYP7A1 Two interacting regulatory SNPs modulate CYP7A1 expression and are associated with risk of coronary artery disease and diabetes mellitus. 30352365 chr8 24381876 24383876 ADAMDEC1 We demonstrated that binding of the enhancer RNAs produced from the upstream enhancer were critically important and that p300 bound to both the RNA from the enhancer and the DNA at the enhancer. P300 binding to the enhancer was dependent on NFκB. These data define the critical pathways regulating the expression of ADAMDEC1 and extend our knowledge of the roles of enhancer RNAs and mechanistically links p300 and enhancer RNAs. human High+Lowthroughput Enhancer RNA and NFκB-dependent P300 regulation of ADAMDEC1 否 Systemic lupus erythematosus Primary monocytes E_01_0662 Luciferase reporter assay, ChIP assays,RNA immunoprecipitation assays We demonstrated that binding of the enhancer RNAs produced from the upstream enhancer were critically important and that p300 bound to both the RNA from the enhancer and the DNA at the enhancer. P300 binding to the enhancer was dependent on NFκB. These data define the critical pathways regulating the expression of ADAMDEC1 and extend our knowledge of the roles of enhancer RNAs and mechanistically links p300 and enhancer RNAs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrated that binding of the enhancer RNAs produced from the upstream enhancer were critically important and that p300 bound to both the RNA from the enhancer and the DNA at the enhancer. P300 binding to the enhancer was dependent on NFκB. These data define the critical pathways regulating the expression of ADAMDEC1 and extend our knowledge of the roles of enhancer RNAs and mechanistically links p300 and enhancer RNAs. Immunohistochemical staining We demonstrated that binding of the enhancer RNAs produced from the upstream enhancer were critically important and that p300 bound to both the RNA from the enhancer and the DNA at the enhancer. P300 binding to the enhancer was dependent on NFκB. These data define the critical pathways regulating the expression of ADAMDEC1 and extend our knowledge of the roles of enhancer RNAs and mechanistically links p300 and enhancer RNAs. Luciferase reporter assay, ChIP assays,RNA immunoprecipitation assays ADAMDEC1 We demonstrated that binding of the enhancer RNAs produced from the upstream enhancer were critically important and that p300 bound to both the RNA from the enhancer and the DNA at the enhancer. P300 binding to the enhancer was dependent on NFκB. These data define the critical pathways regulating the expression of ADAMDEC1 and extend our knowledge of the roles of enhancer RNAs and mechanistically links p300 and enhancer RNAs. 30349303 chr5 34653615 34655615 RAI14 RAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment. human High+Lowthroughput Knockdown of RAI14 suppresses the progression of gastric cancer 否 gastric cancer gastric cancer cell E_01_0663 Western blot,Cell proliferation and colony formation assay,Cell migration assay,Cell apoptosis assay,RT-qPCR RAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment. Immunohistochemical staining RAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment. Western blot,Cell proliferation and colony formation assay,Cell migration assay,Cell apoptosis assay,RT-qPCR RAI14,RAB31 RAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment.;RAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment. 30346835 chr3 13546059 13548059 FBLN2 Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer. human High+Lowthroughput Relationship Between DNA Methylation in Key Region and the Differential Expressions of Genes in Human Breast Tumor Tissue 否 Breast neoplasms breast cancer cell E_01_0664 DNA Methylation Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer. Immunohistochemical staining Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer. DNA Methylation FBLN2,FAT4 Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer.;Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer. 30344724 chr22 39516937 39518937 ATF4 It was indicated that Rg3 exerted pro-apoptotic activity against the gallbladder cancer cell line GBC-SD through the ER stress-mediated signaling pathway. This was demonstrated by increased expression of phosphorylation of eukaryotic translation-initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein homologous protein and lipocalin 2. human High+Lowthroughput Antitumor effect of ginsenoside Rg3 on gallbladder cancer by inducing endoplasmic reticulum stress-mediated apoptosis in vitro and in vivo 否 Gallbladder cancer Gallbladder cancer cell E_01_0665 flow cytometry, western blot analysis, ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR),siRNA sequences synthesis, It was indicated that Rg3 exerted pro-apoptotic activity against the gallbladder cancer cell line GBC-SD through the ER stress-mediated signaling pathway. This was demonstrated by increased expression of phosphorylation of eukaryotic translation-initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein homologous protein and lipocalin 2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It was indicated that Rg3 exerted pro-apoptotic activity against the gallbladder cancer cell line GBC-SD through the ER stress-mediated signaling pathway. This was demonstrated by increased expression of phosphorylation of eukaryotic translation-initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein homologous protein and lipocalin 2. Immunohistochemical staining It was indicated that Rg3 exerted pro-apoptotic activity against the gallbladder cancer cell line GBC-SD through the ER stress-mediated signaling pathway. This was demonstrated by increased expression of phosphorylation of eukaryotic translation-initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein homologous protein and lipocalin 2. flow cytometry, western blot analysis, ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR),siRNA sequences synthesis, ATF4 It was indicated that Rg3 exerted pro-apoptotic activity against the gallbladder cancer cell line GBC-SD through the ER stress-mediated signaling pathway. This was demonstrated by increased expression of phosphorylation of eukaryotic translation-initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CCAAT/enhancer-binding protein homologous protein and lipocalin 2. 30344723 chr7 148804250 148806250 EZH2 Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR 214 in CC. An MTT assay demonstrated that upregulating miR 214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. human High+Lowthroughput microRNA-214 suppresses the growth of cervical cancer cells by targeting EZH2 否 cervical carcinoma cervical cancer cells E_01_0666 Transient transfection,RT‑qPCR,Western blot,Cell proliferation assay,luciferase reporter assay Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR 214 in CC. An MTT assay demonstrated that upregulating miR 214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR 214 in CC. An MTT assay demonstrated that upregulating miR 214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. Immunohistochemical staining Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR 214 in CC. An MTT assay demonstrated that upregulating miR 214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. Transient transfection,RT‑qPCR,Western blot,Cell proliferation assay,luciferase reporter assay EZH2 Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR 214 in CC. An MTT assay demonstrated that upregulating miR 214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. 30343006 chr7 148804374 148806374 EZH2 EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequentlym than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma. human High+Lowthroughput A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas 否 Lung adenocarcinoma promote tumor cell E_01_0667 Immunohistochemical Analyses EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequentlym than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequentlym than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma. Immunohistochemical staining EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequentlym than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma. Immunohistochemical Analyses EZH2 EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequentlym than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma. 30342896 chr8 22685034 22687034 EGR3 Through weighted gene co-expression analysis, EGR3 was found to be related to the keratinocyte differentiation-related module as an important part of the skin-specific genetic network. human High+Lowthroughput EGR3 Is a Late Epidermal Differentiation Regulator that Establishes the Skin-Specific Gene Network 否 Other Human primary epidermal keratinocytes E_01_0668 Quantitative real-time reverse transcriptaseePCR，Immunohistochemistry Through weighted gene co-expression analysis, EGR3 was found to be related to the keratinocyte differentiation-related module as an important part of the skin-specific genetic network. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Through weighted gene co-expression analysis, EGR3 was found to be related to the keratinocyte differentiation-related module as an important part of the skin-specific genetic network. Immunohistochemical staining Through weighted gene co-expression analysis, EGR3 was found to be related to the keratinocyte differentiation-related module as an important part of the skin-specific genetic network. Quantitative real-time reverse transcriptaseePCR，Immunohistochemistry EGR3 Through weighted gene co-expression analysis, EGR3 was found to be related to the keratinocyte differentiation-related module as an important part of the skin-specific genetic network. 30341286 chr7 148804560 148806560 EZH2 Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway. human High+Lowthroughput Targeting enhancer of zeste homolog 2 protects against acute kidney injury 否 Acute kidney injury Proximal tubular epithelial cells E_01_0669 Transfection of siRNA into cells，Immunoblot analyses，Histochemical and immunofluorescence staining Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway. Immunohistochemical staining Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway. Transfection of siRNA into cells，Immunoblot analyses，Histochemical and immunofluorescence staining EZH2 Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway. 30337687 chrX 152895420 152897420 ZNF185 human High+Lowthroughput ZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development 否 Epidermal differentiation and squamous cell carcinoma E_01_0670 Poorly differentiated, including head and neck, cervical and oesophageal, squamous cell carcinomas display loss of ZNF185 expression. Together, these studies reinforce that p63 is a crucial gene for maintaining epithelial tissue integrity and support the deregulation of the cell-cell adhesion programme,which plays a critical role in carcinoma development. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Immunohistochemical staining Poorly differentiated, including head and neck, cervical and oesophageal, squamous cell carcinomas display loss of ZNF185 expression. Together, these studies reinforce that p63 is a crucial gene for maintaining epithelial tissue integrity and support the deregulation of the cell-cell adhesion programme,which plays a critical role in carcinoma development. ZNF185 30335887 chr15 73991784 73993784 PML Collectively, this study uncovers a novel mechanism of PML/RARα mediated transcriptional activation and enriches our knowledge of the onco fusion protein mediated transcription activation. human High+Lowthroughput PML/RARa blocks the differentiation and promotes the proliferation of acute promyelocytic leukemia through activating MYB expression by transcriptional and epigenetic regulation mechanisms 否 Acute promyelocytic leukemia E_01_0671 Chromatin immunoprecipitation‐ sequencing data analysis,Luciferase reporter gene assay,Retrovirus transfection,Reverse transcription‐quantitative real‐time PCR,ChIP‐quantitative PCR Collectively, this study uncovers a novel mechanism of PML/RARα mediated transcriptional activation and enriches our knowledge of the onco fusion protein mediated transcription activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, this study uncovers a novel mechanism of PML/RARα mediated transcriptional activation and enriches our knowledge of the onco fusion protein mediated transcription activation. Immunohistochemical staining Collectively, this study uncovers a novel mechanism of PML/RARα mediated transcriptional activation and enriches our knowledge of the onco fusion protein mediated transcription activation. Chromatin immunoprecipitation‐ sequencing data analysis,Luciferase reporter gene assay,Retrovirus transfection,Reverse transcription‐quantitative real‐time PCR,ChIP‐quantitative PCR PML Collectively, this study uncovers a novel mechanism of PML/RARα mediated transcriptional activation and enriches our knowledge of the onco fusion protein mediated transcription activation. 30325409 chr8 47734236 47736236 CEBPD Thus although our results support the notion that CEBPD acts as a tumor suppressor in HCC, its action does not involve impairing compartment expansion per se but more likely acts through improving anti-cancer immunity. human High+Lowthroughput Action and clinical significance of CCAAT/enhancer-binding protein delta in hepatocellular carcinoma 否 Hepatocellular carcinoma Huh7 , HepG2 cells E_01_0672 Lentiviral-shRNA packaging and infectionWestern blot，Quantitative Real-time PCR(qRT-PCR)，Cell proliferation and Colony formation assa，y Thus although our results support the notion that CEBPD acts as a tumor suppressor in HCC, its action does not involve impairing compartment expansion per se but more likely acts through improving anti-cancer immunity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus although our results support the notion that CEBPD acts as a tumor suppressor in HCC, its action does not involve impairing compartment expansion per se but more likely acts through improving anti-cancer immunity. Immunohistochemical staining Thus although our results support the notion that CEBPD acts as a tumor suppressor in HCC, its action does not involve impairing compartment expansion per se but more likely acts through improving anti-cancer immunity. Lentiviral-shRNA packaging and infectionWestern blot，Quantitative Real-time PCR(qRT-PCR)，Cell proliferation and Colony formation assa，y CEBPD Thus although our results support the notion that CEBPD acts as a tumor suppressor in HCC, its action does not involve impairing compartment expansion per se but more likely acts through improving anti-cancer immunity. 30324804 chr6 106042833 106044833 ATG5 Monitoring expression of ATG5, a key link between autophagy and apoptosis, we established that this correction correlates with reduction of enhanced autophagy activation, a typical feature of thalassemic polychromatophilic normoblasts. human High+Lowthroughput A Novel BaEVRless-Pseudotyped γ-Globin Lentiviral Vector Drives High and Stable Fetal Hemoglobin Expression and Improves Thalassemic Erythropoiesis In Vitro 否 β- Thalassemia major CD34 + cells E_01_0673 quantitative real-time PCR，Flow cytometry and apoptosis assay，cell isolation and transduction Monitoring expression of ATG5, a key link between autophagy and apoptosis, we established that this correction correlates with reduction of enhanced autophagy activation, a typical feature of thalassemic polychromatophilic normoblasts. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Monitoring expression of ATG5, a key link between autophagy and apoptosis, we established that this correction correlates with reduction of enhanced autophagy activation, a typical feature of thalassemic polychromatophilic normoblasts. Immunohistochemical staining Monitoring expression of ATG5, a key link between autophagy and apoptosis, we established that this correction correlates with reduction of enhanced autophagy activation, a typical feature of thalassemic polychromatophilic normoblasts. quantitative real-time PCR，Flow cytometry and apoptosis assay，cell isolation and transduction ATG5 Monitoring expression of ATG5, a key link between autophagy and apoptosis, we established that this correction correlates with reduction of enhanced autophagy activation, a typical feature of thalassemic polychromatophilic normoblasts. 30321476 chr9 134314290 134316290 RXRA We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. human Umbilical cord (fetal) High+Lowthroughput Gestational Vitamin D Supplementation Leads to Reduced Perinatal RXRA DNA Methylation: Results From the MAVIDOS Trial 否 Maternal vitamin D osteoporosis E_01_0674 DNA methylation analysis,Quantitative DNA methylation analysis,RXRA methylation analysis,chemiluminescent assay,chemiluminescent assay,pyrosequencing We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. Immunohistochemical staining We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. DNA methylation analysis,Quantitative DNA methylation analysis,RXRA methylation analysis,chemiluminescent assay,chemiluminescent assay,pyrosequencing RXRA We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. 30321177 chr10 43074329 43076329 RET The p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. human Neoplastic High+Lowthroughput A synonymous RET substitution enhances the oncogenic effect of an in-cis missense mutation by increasing constitutive splicing efficiency 否 Medullary thyroid carcinoma (MTC) HeLa cell E_01_0675 Sanger sequencing,Next-generation sequencing (NGS),Real-time PCR,RNA immunoprecipitation (RIP) The p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. Immunohistochemical staining The p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. Sanger sequencing,Next-generation sequencing (NGS),Real-time PCR,RNA immunoprecipitation (RIP) RET The p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. 30319691 chr8 56158399 56160399 PLAG1 Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptorrelated 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). human High+Lowthroughput Genome-Wide Association and Mechanistic Studies Indicate That Immune Response Contributes to Alzheimer's Disease Development 是 rs2075650,rs157580 Alzheimer disease brain-resident immune cell E_01_0676 quantitative trait loci (eQTL)analysis，immunoassay Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptorrelated 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptorrelated 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). Immunohistochemical staining Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptorrelated 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). quantitative trait loci (eQTL)analysis，immunoassay PLAG1 Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptorrelated 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). 30314898 chr1 202807906 202809906 PCAT6 Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer human normal lung High+Lowthroughput Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer 否 Non small cell carcinoma NSCLC cell E_01_0677 RNA isolation and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)，MTT assay，Flow cytometric analysis，Transwell assay，Western blot analysis，RNA-binding protein immunoprecipitation (RIP) assay，Chromatin immunoprecipitation (ChIP) assays Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer Immunohistochemical staining Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer RNA isolation and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)，MTT assay，Flow cytometric analysis，Transwell assay，Western blot analysis，RNA-binding protein immunoprecipitation (RIP) assay，Chromatin immunoprecipitation (ChIP) assays PCAT6,LATS2 EZH2 Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer;Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer 30310321 chr10 129464370 129466370 MGMT An enhancer variant of MGMT rs10764901 affects the regulatory activity of enhancer by altering the binding affinity of transcription factors and is associated with glioma susceptibility. human High+Lowthroughput An intronic genetic variation of MGMT affects enhancer activity and is associated with glioma susceptibility 是 rs10764901 Gliomas U251 cell E_01_0678 Dual-Luciferase Reporter Assay，electrophoretic mobility shift assays (EMSA)，PCR，Seq An enhancer variant of MGMT rs10764901 affects the regulatory activity of enhancer by altering the binding affinity of transcription factors and is associated with glioma susceptibility. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq An enhancer variant of MGMT rs10764901 affects the regulatory activity of enhancer by altering the binding affinity of transcription factors and is associated with glioma susceptibility. Immunohistochemical staining An enhancer variant of MGMT rs10764901 affects the regulatory activity of enhancer by altering the binding affinity of transcription factors and is associated with glioma susceptibility. Dual-Luciferase Reporter Assay，electrophoretic mobility shift assays (EMSA)，PCR，Seq MGMT An enhancer variant of MGMT rs10764901 affects the regulatory activity of enhancer by altering the binding affinity of transcription factors and is associated with glioma susceptibility. 30307772 chr8 144288777 144290777 HSF1 We show here that theTNF-agene, apleiotropicNkBS inducer, is a direct target of heat shock factor 1 (HSF1). HumanHSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 39-UTR of the TNF-a gene (HSE5). human High+Lowthroughput HSF1 mediated TNF-α production during proteotoxic stress response pioneers proinflammatory signal in human cells 否 Cellular upregulation of the proteotoxic stress response HEK293cell, HCT116cell,PC3cell,HT1080 cell E_01_0679 Chromatin immunoprecipitation,Chromatin conformation capture assay,Semi-quantitative RT-PCR and quantitative RT-PCR,EMSA,MTT cytotoxicity assay,RNA transfection, Immunoprecipitation,Immunoblot We show here that theTNF-agene, apleiotropicNkBS inducer, is a direct target of heat shock factor 1 (HSF1). HumanHSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 39-UTR of the TNF-a gene (HSE5). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show here that theTNF-agene, apleiotropicNkBS inducer, is a direct target of heat shock factor 1 (HSF1). HumanHSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 39-UTR of the TNF-a gene (HSE5). Immunohistochemical staining We show here that theTNF-agene, apleiotropicNkBS inducer, is a direct target of heat shock factor 1 (HSF1). HumanHSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 39-UTR of the TNF-a gene (HSE5). Chromatin immunoprecipitation,Chromatin conformation capture assay,Semi-quantitative RT-PCR and quantitative RT-PCR,EMSA,MTT cytotoxicity assay,RNA transfection, Immunoprecipitation,Immunoblot HSF1 We show here that theTNF-agene, apleiotropicNkBS inducer, is a direct target of heat shock factor 1 (HSF1). HumanHSF1 drives this process by assembling a multiprotein activation complex at a heat shock element (HSE) located at the 39-UTR of the TNF-a gene (HSE5). 30301799 chr3 128476289 128478289 GATA2 By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA- 2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. human High+Lowthroughput Human leukemia mutations corrupt but do not abrogate GATA-2 function 否 Human leukemia mutations E_01_0680 Quantitative Real-Time RT-PCR，Quantitative ChIP，Immunofluorescence，Colony Forming Unit Assay，Flow Cytometry By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA- 2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA- 2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. Immunohistochemical staining By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA- 2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. Quantitative Real-Time RT-PCR，Quantitative ChIP，Immunofluorescence，Colony Forming Unit Assay，Flow Cytometry GATA2 By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA- 2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. 30301396 chr9 81581030 81583030 TLE1 Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel. human High+Lowthroughput Expression of TLE1 in Malignant Melanoma With Spindle Cell Morphology: A Potential Diagnostic Pitfall 否 Malignant melanoma E_01_0681 Immunohistochemical studies Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel. Immunohistochemical staining Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel. Immunohistochemical studies TLE1 Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel. 30297428 chr6 100382241 100384241 SIM1 The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536- T risk allele showed differential enhancer activity. human High+Lowthroughput Genetic variation in the SIM1 locus is associated with erectile dysfunction 是 rs17185536 erectile dysfunction HEK 293T E_01_0682 GWAS Analysis，Luciferase Assays The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536- T risk allele showed differential enhancer activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536- T risk allele showed differential enhancer activity. Immunohistochemical staining The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536- T risk allele showed differential enhancer activity. GWAS Analysis，Luciferase Assays SIM1 The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536- T risk allele showed differential enhancer activity. 30296588 chr7 117284315 117286315 CFTR These data suggest that CFTR regulatory elements may harbor novel CF disease causing variants that warrant further investigation, both for genetic screening protocols and functional assays. human High+Lowthroughput Screening for Regulatory Variants in 460 kb Encompassing the CFTR Locus in Cystic Fibrosis Patients 否 Cystic fibrosis Caco228 cell，16HBE14o-29 cell E_01_0683 Transient Luciferase Assays， transient assays，Dual-Luciferase Reporter Assay，Bioinformatic Variant Analysis These data suggest that CFTR regulatory elements may harbor novel CF disease causing variants that warrant further investigation, both for genetic screening protocols and functional assays. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These data suggest that CFTR regulatory elements may harbor novel CF disease causing variants that warrant further investigation, both for genetic screening protocols and functional assays. Immunohistochemical staining These data suggest that CFTR regulatory elements may harbor novel CF disease causing variants that warrant further investigation, both for genetic screening protocols and functional assays. Transient Luciferase Assays， transient assays，Dual-Luciferase Reporter Assay，Bioinformatic Variant Analysis CFTR These data suggest that CFTR regulatory elements may harbor novel CF disease causing variants that warrant further investigation, both for genetic screening protocols and functional assays. 30293785 chr20 47206342 47208342 ZMYND8 ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 30 Igh super-enhancer. human High+Lowthroughput The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination 否 Other CH12 cell E_01_0684 Retroviral Infection,Immunoisolation of RIF1FH Complexes,Mass Spectrometric Analysis,CRISPR-Cas9 Gene Targeting,Cell Lysates and CoIP Assay,Flow Cytometry,Quantitative PCR,Immunofluorescence,Clonogenic Assay,Metaphase Analysis,End Resection Assay,CRISPR-Cas9-Induced CSR Assay,MutPE-Seq,ChIP-Seq,RNA-Seq,GRO-Seq,Switch Junction Analysis,SHM Analysis ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 30 Igh super-enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 30 Igh super-enhancer. Immunohistochemical staining ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 30 Igh super-enhancer. Retroviral Infection,Immunoisolation of RIF1FH Complexes,Mass Spectrometric Analysis,CRISPR-Cas9 Gene Targeting,Cell Lysates and CoIP Assay,Flow Cytometry,Quantitative PCR,Immunofluorescence,Clonogenic Assay,Metaphase Analysis,End Resection Assay,CRISPR-Cas9-Induced CSR Assay,MutPE-Seq,ChIP-Seq,RNA-Seq,GRO-Seq,Switch Junction Analysis,SHM Analysis ZMYND8 ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 30 Igh super-enhancer. 30286132 chr17 39725638 39727638 MIEN1 Knocking out MIEN1 in these breast cancer cells will allow future studies to determine the exact role MIEN1 plays in breast tumor metastasis, which might lead to production of novel therapeutics to treat this and other caners human High+Lowthroughput CRISPR deletion of MIEN1 in breast cancer cells 否 mammary cancer breast cancer cell E_01_0685 Transfection and CRISPR genome editing，Sequencing，Western blot Knocking out MIEN1 in these breast cancer cells will allow future studies to determine the exact role MIEN1 plays in breast tumor metastasis, which might lead to production of novel therapeutics to treat this and other caners Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Knocking out MIEN1 in these breast cancer cells will allow future studies to determine the exact role MIEN1 plays in breast tumor metastasis, which might lead to production of novel therapeutics to treat this and other caners Immunohistochemical staining Knocking out MIEN1 in these breast cancer cells will allow future studies to determine the exact role MIEN1 plays in breast tumor metastasis, which might lead to production of novel therapeutics to treat this and other caners Transfection and CRISPR genome editing，Sequencing，Western blot MIEN1 Knocking out MIEN1 in these breast cancer cells will allow future studies to determine the exact role MIEN1 plays in breast tumor metastasis, which might lead to production of novel therapeutics to treat this and other caners 30285829 chr16 50739227 50741227 CYLD Via its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA. human Synovial High+Lowthroughput CYLD suppression enhances the pro-inflammatory effects and hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes by enhancing NF-κB activation 否 Rheumatoid arthritis synovial cell E_01_0686 Immunohistochemistry (IHC),Immunofluorescence (IF) staining,RT-PCR,Western blot,ELISA,Cell proliferation assay,y flow cytometry Via its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Via its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA. Immunohistochemical staining Via its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA. Immunohistochemistry (IHC),Immunofluorescence (IF) staining,RT-PCR,Western blot,ELISA,Cell proliferation assay,y flow cytometry CYLD Via its regulation of NF-κB activation, CYLD may be involved in the pathogenesis of synovial inflammation in RA as well as in the pro-inflammatory effects and hyperproliferation of RA-FLSs. CYLD may therefore provide a potential target for the treatment of RA. 30283292 chr1 161763468 161765468 ATF6 Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway. human High+Lowthroughput Melatonin Protects Against Neuronal Apoptosis via Suppression of the ATF6/CHOP Pathway in a Rat Model of Intracerebral Hemorrhage 否 cerebral hemorrhage neuronal cell E_01_0687 Evans Blue (EB) Staining，Immunofluorescence，Western Blot，Small Interfering RNA and Intracerebroventricular Injection，RT-PCR Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway. Immunohistochemical staining Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway. Evans Blue (EB) Staining，Immunofluorescence，Western Blot，Small Interfering RNA and Intracerebroventricular Injection，RT-PCR ATF6 Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway. 30276662 chr13 83649606 83651606 Mef2c Thus, our results reveal the specific expression and functionalrelevance of Mef2c in developing Purkinje cells and offer insight to how disruption of the expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of cerebellar-associated disorders. mouse High+Lowthroughput Myocyte Enhancer Factor 2c Regulates Dendritic Complexity and Connectivity of Cerebellar Purkinje Cells 否 Purkinje cell E_01_0688 situ hybridization analysis，immunohistochemical analysis Thus, our results reveal the specific expression and functionalrelevance of Mef2c in developing Purkinje cells and offer insight to how disruption of the expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of cerebellar-associated disorders. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, our results reveal the specific expression and functionalrelevance of Mef2c in developing Purkinje cells and offer insight to how disruption of the expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of cerebellar-associated disorders. Immunohistochemical staining Thus, our results reveal the specific expression and functionalrelevance of Mef2c in developing Purkinje cells and offer insight to how disruption of the expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of cerebellar-associated disorders. situ hybridization analysis，immunohistochemical analysis Mef2c Thus, our results reveal the specific expression and functionalrelevance of Mef2c in developing Purkinje cells and offer insight to how disruption of the expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of cerebellar-associated disorders. 30274685 chr7 148804548 148806548 EZH2 MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma human High+Lowthroughput MiR-137 suppresses migration and invasion by targeting EZH2-STAT3 signaling in human hepatocellular carcinoma 否 Human hepatocellular carcinoma hepatocellular carcinoma cell E_01_0689 Cell transfection，qPCR，Wound-healing assay，Transwell assay，Dual-luciferase reporter assay， Western blotting analysis MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma Immunohistochemical staining MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma Cell transfection，qPCR，Wound-healing assay，Transwell assay，Dual-luciferase reporter assay， Western blotting analysis EZH2,STAT3 MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma;MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma 30270123 chr7 27159901 27161901 HOXA9 Therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression. human High+Lowthroughput HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis 否 leukemia progenitor cell E_01_0690 Flow Cytometry,Cell Proliferation and Colony Formation Assays,Immunoprecipitation,4C-seq Analysis,ChIP, ChIP-Seq and Bioinformatics Analyses,Real-time PCR and RNA-seq Analyses,Global Analysis on the Enhancer Landscape Therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression. Immunohistochemical staining Therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression. Flow Cytometry,Cell Proliferation and Colony Formation Assays,Immunoprecipitation,4C-seq Analysis,ChIP, ChIP-Seq and Bioinformatics Analyses,Real-time PCR and RNA-seq Analyses,Global Analysis on the Enhancer Landscape HOXA9 Therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression. 30266822 chr20 32355424 32357424 ASXL1 Thus, in addition to promoting myeloid malignancies, ASXL1 controls epigenetic reprogramming of osteoclasts to regulate bone resorption and mass. human High+Lowthroughput ASXL1 impairs osteoclast formation by epigenetic regulation of NFATc1 否 Myeloid malignancies osteoclast E_01_0691 Histone extraction, histone western blot，Lentivirus infection，ChIP assay，ChIP-seq Thus, in addition to promoting myeloid malignancies, ASXL1 controls epigenetic reprogramming of osteoclasts to regulate bone resorption and mass. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, in addition to promoting myeloid malignancies, ASXL1 controls epigenetic reprogramming of osteoclasts to regulate bone resorption and mass. Immunohistochemical staining Thus, in addition to promoting myeloid malignancies, ASXL1 controls epigenetic reprogramming of osteoclasts to regulate bone resorption and mass. Histone extraction, histone western blot，Lentivirus infection，ChIP assay，ChIP-seq ASXL1 Thus, in addition to promoting myeloid malignancies, ASXL1 controls epigenetic reprogramming of osteoclasts to regulate bone resorption and mass. 30262664 chr14 100891966 100893966 MEG8 Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. human High+Lowthroughput MEG8 long noncoding RNA contributes to epigenetic progression of the epithelial-mesenchymal transition of lung and pancreatic cancer cells 否 Lung and pancreatic cancer A549 cell， LC-2/ad cell，Panc1 cell E_01_0692 Quantitative PCR，Cell migration assay，Chromatin immunoprecipitation (ChIP) assays，RNA immunoprecipitation (RIP)，Chromatin isolation by RNA purification (ChIRP) assays Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. Immunohistochemical staining Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. Quantitative PCR，Cell migration assay，Chromatin immunoprecipitation (ChIP) assays，RNA immunoprecipitation (RIP)，Chromatin isolation by RNA purification (ChIRP) assays MEG8 Our findings indicate that MEG8 lncRNA significantly contributes to epigenetic EMT induction and increase our understanding of the lncRNA-mediated regulatory mechanisms involved in malignant progression of cancer. 30259241 chr12 55740136 55742136 GDF11 Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. human High+Lowthroughput GDF11 Antagonizes Psoriasis-like Skin Inflammation via Suppression of NF-κB Signaling Pathway 否 Psoriasiform skin inflammation Mouse leukemic monocyte macrophages E_01_0693 miRNA transfection，Real-Time PCR,Western Blot,Immunofluorescence,ELISA Assays Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. Immunohistochemical staining Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. miRNA transfection，Real-Time PCR,Western Blot,Immunofluorescence,ELISA Assays GDF11 Additionally, the activation of nuclear NF-κB (nuclear factor κ-light-chainenhancer of activated B cells) signaling pathway was repressed by GDF11 treatment. Collectively, GDF11 may represent a promising molecular target for the prevention and treatment of psoriasis-like skin inflammation. 30257372 chr8 127077104 127079104 PRNCR1 Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. human High+Lowthroughput LncRNA PRNCR1 interacts with HEY2 to abolish miR-448-mediated growth inhibition in non-small cell lung cancer 否 Non small cell lung cancer A549 cell, SK-MES-1 cell, Calu-3 cell，H1299 cell，NHBE cell E_01_0694 Cell transfection,RNA isolation,qRT-PCR analysi, Cell proliferation assays, Transwell assays,Luciferase reporter analysis,RIP assay, Western blot assay Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Immunohistochemical staining Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Cell transfection,RNA isolation,qRT-PCR analysi, Cell proliferation assays, Transwell assays,Luciferase reporter analysis,RIP assay, Western blot assay PRNCR1 HEY2 Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. Taken all together, we confirmed that lncRNA PRNCR1 upregulates HEY2 to promote tumor progression in NSCLC by competitively binding miR-448. 30256540 chr16 55386943 55388943 MMP2 These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer human High+Lowthroughput TGF-β-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression 否 lung cancer E_01_0695 qRT-PCR,Immunofluorescence,Western blot,Wound healing assay,Transwell assays,Luciferase assay,Immunohistochemistry and in situ hybridization These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer Immunohistochemical staining These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer qRT-PCR,Immunofluorescence,Western blot,Wound healing assay,Transwell assays,Luciferase assay,Immunohistochemistry and in situ hybridization MMP2 These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer 30252132 chr4 74442566 74444566 AREG Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. human High+Lowthroughput Epigenetic regulation of Amphiregulin and Epiregulin in colorectal cancer 否 colorectal cancer SW480 cell，RKO cell，HCT116 cell，Caco2 cell E_01_0696 RNA isolation and Real-time PCR analysis,Methylation analysis,Luciferase reporter analysis,immunohistochemistry Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Immunohistochemical staining Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. RNA isolation and Real-time PCR analysis,Methylation analysis,Luciferase reporter analysis,immunohistochemistry AREG,EREG Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. ;Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. 30250574 chr16 69704597 69706597 NQO1 STE unregulated phosphorylated p53, NF κB p65, Nrf2, HO 1, and NQO1 expression levels in the hOMF cells. The present study demonstrated that STE appears to promote oral disease. human High+Lowthroughput Smokeless tobacco extract inhibits proliferation and promotes apoptosis in oral mucous fibroblasts 否 Diabetes, inflammation, cancer fibroblast E_01_0697 RT‑qPCR,Western blot,Cell viability assay,Immunofluorescence assay,Flow cytometric analysis STE unregulated phosphorylated p53, NF κB p65, Nrf2, HO 1, and NQO1 expression levels in the hOMF cells. The present study demonstrated that STE appears to promote oral disease. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq STE unregulated phosphorylated p53, NF κB p65, Nrf2, HO 1, and NQO1 expression levels in the hOMF cells. The present study demonstrated that STE appears to promote oral disease. Immunohistochemical staining STE unregulated phosphorylated p53, NF κB p65, Nrf2, HO 1, and NQO1 expression levels in the hOMF cells. The present study demonstrated that STE appears to promote oral disease. RT‑qPCR,Western blot,Cell viability assay,Immunofluorescence assay,Flow cytometric analysis NQO1 STE unregulated phosphorylated p53, NF κB p65, Nrf2, HO 1, and NQO1 expression levels in the hOMF cells. The present study demonstrated that STE appears to promote oral disease. 30245028 chr3 128476533 128478533 GATA2 The rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. human High+Lowthroughput An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F 是 rs2523393 Other endometrial stromal cell E_01_0698 ChIP-Seq,Luciferase Assays, Hi-C The rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. Immunohistochemical staining The rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. ChIP-Seq,Luciferase Assays, Hi-C GATA2 The rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. 30228822 chr17 42697888 42699888 EZH1 In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. human High+Lowthroughput EZH1 Is Associated with TCP-Induced Bone Regeneration through Macrophage Polarization 否 Other THP-1 cell E_01_0699 Hematoxylin-Eosin Staining,Alizarin Red Staining and Alkaline Phosphatase Staining,Western Blotting,Protein Extraction,Reverse Transcription and Quantitative PCR In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Immunohistochemical staining In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Hematoxylin-Eosin Staining,Alizarin Red Staining and Alkaline Phosphatase Staining,Western Blotting,Protein Extraction,Reverse Transcription and Quantitative PCR EZH1 In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. 30226578 chr9 134132591 134134591 WDR5 These results further understanding of a potential post-translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis. human High+Lowthroughput Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration 否 mammary cancer breast cancer cell E_01_0700 In vitro methylation assay and mass spectrometry analysis,Immunoprecipitation,Western blotting,Colony formation assay,Wound healing and cell migration assay These results further understanding of a potential post-translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results further understanding of a potential post-translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis. Immunohistochemical staining These results further understanding of a potential post-translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis. In vitro methylation assay and mass spectrometry analysis,Immunoprecipitation,Western blotting,Colony formation assay,Wound healing and cell migration assay WDR5 These results further understanding of a potential post-translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis. 30219228 chr4 15601897 15603897 FBXL5 Our researches suggest that miR-1306e3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306e3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC. human primary HCC tissues High+Lowthroughput miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma through suppressing snail degradation 否 Hepatocellular carcinoma E_01_0701 Lentivirus infection,Transient transfection,RNA isolation, reverse transcription, QPCR,Transwell and boyden assays,Wound healing assay,Western blot, Luciferase reporter assay, Chromatin immunoprecipitation assay,In situ hybridization (ISH),Immunohistochemistry (IHC) Our researches suggest that miR-1306e3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306e3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our researches suggest that miR-1306e3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306e3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC. Immunohistochemical staining Our researches suggest that miR-1306e3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306e3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC. Lentivirus infection,Transient transfection,RNA isolation, reverse transcription, QPCR,Transwell and boyden assays,Wound healing assay,Western blot, Luciferase reporter assay, Chromatin immunoprecipitation assay,In situ hybridization (ISH),Immunohistochemistry (IHC) FBXL5 Our researches suggest that miR-1306e3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306e3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC. 29436621 chr18 55219776 55221776 TCF4 This implied that a high expression of TCF4 isoforms may lead to Wnt/β-catenin signal activation and potentially promote malignant glioma development. human High+Lowthroughput Expression and functional analysis of TCF4 isoforms in human glioma cells 否 Human gliomas U251cell,A172cell,U-87MGcell E_01_0702 RT‑PCR, cell transfection,MTT assay,Flow cytometry,Wound healing assay This implied that a high expression of TCF4 isoforms may lead to Wnt/β-catenin signal activation and potentially promote malignant glioma development. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This implied that a high expression of TCF4 isoforms may lead to Wnt/β-catenin signal activation and potentially promote malignant glioma development. Immunohistochemical staining This implied that a high expression of TCF4 isoforms may lead to Wnt/β-catenin signal activation and potentially promote malignant glioma development. RT‑PCR, cell transfection,MTT assay,Flow cytometry,Wound healing assay TCF4 This implied that a high expression of TCF4 isoforms may lead to Wnt/β-catenin signal activation and potentially promote malignant glioma development. 29435295 chr7 148804639 148806639 EZH2 None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy. human High+Lowthroughput Identification of candidate responders for anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitory therapy in small-cell lung cancer 否 small cell lung cancer SCLC cell E_01_0703 Immunohistochemical (IHC) staining None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy. Immunohistochemical staining None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy. Immunohistochemical (IHC) staining EZH2 None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy. 29435081 chr8 127397745 127399745 CCAT2 Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer. human High+Lowthroughput Long non-coding RNA CCAT2 promotes epithelial-mesenchymal transition involving Wnt/β-catenin pathway in epithelial ovarian carcinoma cells 否 oophoroma Epithelial ovarian cancer cell E_01_0704 Total RNA extraction,RT‑qPCR,Small interfering RNAs (siRNAs) and transfection,Monolayer wound healing assay,Transwell invasion assay,Western blot,TOP‑FLASH luciferase assay Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer. Immunohistochemical staining Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer. Total RNA extraction,RT‑qPCR,Small interfering RNAs (siRNAs) and transfection,Monolayer wound healing assay,Transwell invasion assay,Western blot,TOP‑FLASH luciferase assay CCAT2 Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer. 29435063 chr7 148803958 148805958 EZH2 The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy human High+Lowthroughput Inhibition of enhancer of zeste homolog 2 increases the expression of p16 and suppresses the proliferation and migration of ovarian carcinoma cells in vitro and in vivo 否 oophoroma A2780cell,SKOV3cell E_01_0705 Lentivirus construction and transduction，RNA extraction，RT‑qPCR,Protein isolation,western blot analysis,Cell proliferation assay,Cell migration assay The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy Immunohistochemical staining The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy Lentivirus construction and transduction，RNA extraction，RT‑qPCR,Protein isolation,western blot analysis,Cell proliferation assay,Cell migration assay EZH2 The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy 29435024 chr7 148804550 148806550 EZH2 The data presented in the present study is the first to indicate that EZH2 is upregulated in CRC and may serve as a predictor of poor outcome for patients with CRC. human High+Lowthroughput Expression of EZH2 is associated with poor outcome in colorectal cancer 否 colorectal cancer HCEC cell E_01_0706 RNA interference,Cell proliferation assay,RT‑qPCR,Western blot,Immunohistochemical analysis The data presented in the present study is the first to indicate that EZH2 is upregulated in CRC and may serve as a predictor of poor outcome for patients with CRC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The data presented in the present study is the first to indicate that EZH2 is upregulated in CRC and may serve as a predictor of poor outcome for patients with CRC. Immunohistochemical staining The data presented in the present study is the first to indicate that EZH2 is upregulated in CRC and may serve as a predictor of poor outcome for patients with CRC. RNA interference,Cell proliferation assay,RT‑qPCR,Western blot,Immunohistochemical analysis EZH2 The data presented in the present study is the first to indicate that EZH2 is upregulated in CRC and may serve as a predictor of poor outcome for patients with CRC. 29432919 chr11 102107729 102109729 YAP1 Our results revealed the essential role of YAP1 and the YAP1-TEADs complex in regulating osteoclastogenesis and related gene expression. human High+Lowthroughput YAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism 否 Other Bone marrow-derived macrophages E_01_0707 Quantitative real-time PCR,Co-immunoprecipitation, Western blotting, Electrophoretic mobility shift assay Our results revealed the essential role of YAP1 and the YAP1-TEADs complex in regulating osteoclastogenesis and related gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results revealed the essential role of YAP1 and the YAP1-TEADs complex in regulating osteoclastogenesis and related gene expression. Immunohistochemical staining Our results revealed the essential role of YAP1 and the YAP1-TEADs complex in regulating osteoclastogenesis and related gene expression. Quantitative real-time PCR,Co-immunoprecipitation, Western blotting, Electrophoretic mobility shift assay YAP1 Our results revealed the essential role of YAP1 and the YAP1-TEADs complex in regulating osteoclastogenesis and related gene expression. 29425687 chr17 42310341 42312341 STAT3 These dual functions of ASCJ9 to suppress PCa proliferation and invasion (via altering STAT3 sumoylation) may help us to develop a better anti-AR compound that may overcome the current antiandrogens unwanted side of increasing the metastasis to better suppress the castration-resistant PCa progression. human High+Lowthroughput ASC-J9(?) suppresses prostate cancer cell invasion via altering the sumoylation-phosphorylation of STAT3 否 prostatic cancer prostate cancer cell E_01_0708 Cell Invasion Assay,3D invasion assay,Quantitative PCR,Western Blot,Transient transfection,Lentiviral expression system,Immunoprecipitation assay,ChIP assay These dual functions of ASCJ9 to suppress PCa proliferation and invasion (via altering STAT3 sumoylation) may help us to develop a better anti-AR compound that may overcome the current antiandrogens unwanted side of increasing the metastasis to better suppress the castration-resistant PCa progression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These dual functions of ASCJ9 to suppress PCa proliferation and invasion (via altering STAT3 sumoylation) may help us to develop a better anti-AR compound that may overcome the current antiandrogens unwanted side of increasing the metastasis to better suppress the castration-resistant PCa progression. Immunohistochemical staining These dual functions of ASCJ9 to suppress PCa proliferation and invasion (via altering STAT3 sumoylation) may help us to develop a better anti-AR compound that may overcome the current antiandrogens unwanted side of increasing the metastasis to better suppress the castration-resistant PCa progression. Cell Invasion Assay,3D invasion assay,Quantitative PCR,Western Blot,Transient transfection,Lentiviral expression system,Immunoprecipitation assay,ChIP assay STAT3 These dual functions of ASCJ9 to suppress PCa proliferation and invasion (via altering STAT3 sumoylation) may help us to develop a better anti-AR compound that may overcome the current antiandrogens unwanted side of increasing the metastasis to better suppress the castration-resistant PCa progression. 29425513 chr8 38139436 38141436 STAR Organoid technology, in combi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_nation with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. human High+Lowthroughput Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene 是 colorectal cancer Human Colorectal Organoids Stem Cell E_01_0709 Cell Transfection,Dual-Luciferase Assay,RNA Sequencing,Orthotopic Xenotransplantation of Organoids, FACS analysis Organoid technology, in combi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_nation with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Organoid technology, in combi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_nation with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. Immunohistochemical staining Organoid technology, in combi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_nation with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. Cell Transfection,Dual-Luciferase Assay,RNA Sequencing,Orthotopic Xenotransplantation of Organoids, FACS analysis STAR Organoid technology, in combi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_nation with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. 29420098 chr19 49673051 49675051 PRMT1 In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1) induced Smad6 methylation. human High+Lowthroughput Smad6 Methylation Represses NFκB Activation and Periodontal Inflammation 否 Periodontal inflammation HaCaT cell E_01_0710 immunoblotting In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1) induced Smad6 methylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1) induced Smad6 methylation. Immunohistochemical staining In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1) induced Smad6 methylation. immunoblotting PRMT1 In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1) induced Smad6 methylation. 29416002 chr7 148804302 148806302 EZH2 Overall, these findings revealed that EZH2 affects ACD of VSMCs and the pathologic process of AD via regulating ATG5 and ATG7 expression and MEK ERK1/2 signaling. Our hitherto unrecognized findings indicate that EZH2 activation has therapeutic or preventive potential for AD. human High+Lowthroughput EZH2 inhibits autophagic cell death of aortic vascular smooth muscle cells to affect aortic dissection 否 dissection of aorta blood vessel smooth muscle cell E_01_0711 Western blot，Real-time PCR，Immunofluorescence analysis，Flow cytometry Overall, these findings revealed that EZH2 affects ACD of VSMCs and the pathologic process of AD via regulating ATG5 and ATG7 expression and MEK ERK1/2 signaling. Our hitherto unrecognized findings indicate that EZH2 activation has therapeutic or preventive potential for AD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overall, these findings revealed that EZH2 affects ACD of VSMCs and the pathologic process of AD via regulating ATG5 and ATG7 expression and MEK ERK1/2 signaling. Our hitherto unrecognized findings indicate that EZH2 activation has therapeutic or preventive potential for AD. Immunohistochemical staining Overall, these findings revealed that EZH2 affects ACD of VSMCs and the pathologic process of AD via regulating ATG5 and ATG7 expression and MEK ERK1/2 signaling. Our hitherto unrecognized findings indicate that EZH2 activation has therapeutic or preventive potential for AD. Western blot，Real-time PCR，Immunofluorescence analysis，Flow cytometry EZH2 Overall, these findings revealed that EZH2 affects ACD of VSMCs and the pathologic process of AD via regulating ATG5 and ATG7 expression and MEK ERK1/2 signaling. Our hitherto unrecognized findings indicate that EZH2 activation has therapeutic or preventive potential for AD. 29415998 chr7 117284540 117286540 CFTR In conclusion, our study showed that Hcy activates autophagy by inhibition of CFTR expression via interaction between H3K27me3 and DNA methylation in the mouse liver. These findings provide new insight into the mechanism of Hcyinduced autophagy in liver injury human Liver High+Lowthroughput Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver 否 Liver injury HL-7702 cell E_01_0712 Quantitative real-time PCR,Western blot,Chromatin immunoprecipitation (ChIP) assays,Bisulfite sequencing,RNA interference In conclusion, our study showed that Hcy activates autophagy by inhibition of CFTR expression via interaction between H3K27me3 and DNA methylation in the mouse liver. These findings provide new insight into the mechanism of Hcyinduced autophagy in liver injury Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, our study showed that Hcy activates autophagy by inhibition of CFTR expression via interaction between H3K27me3 and DNA methylation in the mouse liver. These findings provide new insight into the mechanism of Hcyinduced autophagy in liver injury Immunohistochemical staining In conclusion, our study showed that Hcy activates autophagy by inhibition of CFTR expression via interaction between H3K27me3 and DNA methylation in the mouse liver. These findings provide new insight into the mechanism of Hcyinduced autophagy in liver injury Quantitative real-time PCR,Western blot,Chromatin immunoprecipitation (ChIP) assays,Bisulfite sequencing,RNA interference CFTR In conclusion, our study showed that Hcy activates autophagy by inhibition of CFTR expression via interaction between H3K27me3 and DNA methylation in the mouse liver. These findings provide new insight into the mechanism of Hcyinduced autophagy in liver injury 29413899 chr1 212562611 212564611 ATF3 Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals. human High+Lowthroughput Regulation of the ATF3 gene by a single promoter in response to amino acid availability and endoplasmic reticulum stress in human primary hepatocytes and hepatoma cells 否 inflammation HCC cell E_01_0713 Protein isolation and immunoblotting,RNA isolation,RT-qPCR, Chromatin immunoprecipitation (ChIP) Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals. Immunohistochemical staining Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals. Protein isolation and immunoblotting,RNA isolation,RT-qPCR, Chromatin immunoprecipitation (ChIP) ATF3 Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals. 29413056 chr7 55016381 55018381 EGFR This study demonstrated that ILF3 plays an oncogenic like role in maintaining the EGFR-mediated cellular pathway, and can be a therapeutic target to improve the therapeutic efficacy of afatinib. Our results suggested that YM155, an ILF3 inhibitor, has the potential for utilization in cancer therapy against EGFR-positive lung cancers human High+Lowthroughput EGFR-mediated interleukin enhancer-binding factor 3 contributes to formation and survival of cancer stem-like tumorspheres as a therapeutic target against EGFR-positive non-small cell lung cancer 否 Non small cell lung cancer HCC827 cell ，A549 cell E_01_0714 mRNA extraction,Quantitative PCR,Gene knockdown, Western blotting,Cell viability, RNAseq This study demonstrated that ILF3 plays an oncogenic like role in maintaining the EGFR-mediated cellular pathway, and can be a therapeutic target to improve the therapeutic efficacy of afatinib. Our results suggested that YM155, an ILF3 inhibitor, has the potential for utilization in cancer therapy against EGFR-positive lung cancers Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study demonstrated that ILF3 plays an oncogenic like role in maintaining the EGFR-mediated cellular pathway, and can be a therapeutic target to improve the therapeutic efficacy of afatinib. Our results suggested that YM155, an ILF3 inhibitor, has the potential for utilization in cancer therapy against EGFR-positive lung cancers Immunohistochemical staining This study demonstrated that ILF3 plays an oncogenic like role in maintaining the EGFR-mediated cellular pathway, and can be a therapeutic target to improve the therapeutic efficacy of afatinib. Our results suggested that YM155, an ILF3 inhibitor, has the potential for utilization in cancer therapy against EGFR-positive lung cancers mRNA extraction,Quantitative PCR,Gene knockdown, Western blotting,Cell viability, RNAseq EGFR This study demonstrated that ILF3 plays an oncogenic like role in maintaining the EGFR-mediated cellular pathway, and can be a therapeutic target to improve the therapeutic efficacy of afatinib. Our results suggested that YM155, an ILF3 inhibitor, has the potential for utilization in cancer therapy against EGFR-positive lung cancers 29374067 chr13 26129178 26131178 RNF6 TLE3 expression abolished the oncogenic effects of RNF6,and RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis. human High+Lowthroughput RNF6 Promotes Colorectal Cancer by Activating the Wnt/β-Catenin Pathway via Ubiquitination of TLE3 否 colorectal cancer E_01_0715 DNA extraction,DNA copy number Real-time PCR,Co-immunoprecipitation,mass spectrometry,Ubiquitination Assay,Luciferase reporter activity analysis TLE3 expression abolished the oncogenic effects of RNF6,and RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TLE3 expression abolished the oncogenic effects of RNF6,and RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis. Immunohistochemical staining TLE3 expression abolished the oncogenic effects of RNF6,and RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis. DNA extraction,DNA copy number Real-time PCR,Co-immunoprecipitation,mass spectrometry,Ubiquitination Assay,Luciferase reporter activity analysis RNF6 TLE3 TLE3 expression abolished the oncogenic effects of RNF6,and RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis. TLE3 expression abolished the oncogenic effects of RNF6,and RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis. 29373533 chr13 40552808 40554808 FOXO1 These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes. human High+Lowthroughput Suppression of Fatty Acid and Triglyceride Synthesis by the Flavonoid Orientin through Decrease of C/EBPδ Expression and Inhibition of PI3K/Akt-FOXO1 Signaling in Adipocytes 否 Obesity 3T3-L1 cell E_01_0716 Cytotoxicity Assay,Quantitative PCR,Western Blot,Cell Proliferation Assay,Chromatin Immunoprecipitation Assay These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes. Immunohistochemical staining These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes. Cytotoxicity Assay,Quantitative PCR,Western Blot,Cell Proliferation Assay,Chromatin Immunoprecipitation Assay FOXO1 These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes. 29369995 chr9 92410003 92412003 OMD Proteome analysis validated by immunohistochemistry may pro_x005f_x0002_vide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required. human High+Lowthroughput Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency 否 Craniosynostosis E_01_0717 Liquid Chromatography–Tandem Mass Spectrometry Analysis, Proteome analysis validated by immunohistochemistry may pro_x005f_x0002_vide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Proteome analysis validated by immunohistochemistry may pro_x005f_x0002_vide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required. Immunohistochemical staining Proteome analysis validated by immunohistochemistry may pro_x005f_x0002_vide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required. Liquid Chromatography–Tandem Mass Spectrometry Analysis, OMD Proteome analysis validated by immunohistochemistry may pro_x005f_x0002_vide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required. 29369390 chr13 27957641 27959641 CDX2 This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for pilomatrical carcinoma, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors. human High+Lowthroughput CDX2 and LEF-1 expression in pilomatrical tumors and their utility in the diagnosis of pilomatrical carcinoma 否 Hairy tumors squamous cell E_01_0718 Immunohistochemical analysis This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for pilomatrical carcinoma, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for pilomatrical carcinoma, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors. Immunohistochemical staining This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for pilomatrical carcinoma, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors. Immunohistochemical analysis CDX2 This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for pilomatrical carcinoma, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors. 30218753 chr7 148804161 148806161 EZH2 EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. human High+Lowthroughput Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis. 否 cancer tumor cell E_01_0719 Immunohistochemistry (IHC), chip PCR, Weston blot, flow cytometry EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. Immunohistochemical staining EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. 免疫组化(IHC),ChIP-PCR ,weston blot,流式细胞术 EZH2 EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. 30218754 chr7 148804774 148806774 EZH2 EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. human High+Lowthroughput Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell lymphoma, nasal type, is associated with disease progression and prognosis. 否 cancer T cell E_01_0720 Immunohistochemistry (IHC), chip PCR, Weston blot, flow cytometry EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. Immunohistochemical staining EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. 免疫组化(IHC),ChIP-PCR ,weston blot,流式细胞术 EZH2 EZH2 overexpression was significantly associated with higher tumor cell proliferation (r=0.582, P=0.000), advanced stage (P=0.012), and predicted poorer overall survival (OS) (P=0.016) in ENKTL. 30217225 chr3 133743403 133745403 TF Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. human High+Lowthroughput Genomic analysis of transcriptional networks directing progression of cell states during MGE development. 否 E_01_0721 RT qPCR, in situ hybridization analysis, gene knockdown, chip SEQ, immunofluorescence staining Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. Immunohistochemical staining Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. RT-qPCR,原位杂交分析,基因敲降,ChIP-seq ,免疫荧光染色 TF,LHX6,LHX8 Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8.;Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8.;Background Homeodomain (HD) transcription factor (TF) NKX2 1 critical for the regional specification of the medial ganglionic eminence (MGE) as well as promoting the GABAergic and cholinergic neuron fates via the induction of TFs such as LHX6 and LHX8. 30214574 chr1 1612343 1614343 MIB2 The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. human High+Lowthroughput Ectopic expression of E3 ubiquitin-protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ-light-chain-enhancer of B cells. 否 Tumor glioma Glioma cell E_01_0722 RT qPCR, gene knockdown, Weston blot The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. Immunohistochemical staining The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. RT-qPCR,基因敲降,weston blot MIB2 The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. 30212590 chr16 10863348 10865348 CIITA Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. human High+Lowthroughput Impact of human sepsis on CCCTC-binding factor associated monocyte transcriptional response of Major Histocompatibility Complex II components. 否 Immunosuppressed patients, sepsis T cell E_01_0723 ChIP-seq,PCR Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. Immunohistochemical staining Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. ChIP-seq,PCR CIITA CTCF Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. 30212242 chr6 117450516 117452516 DCBLD1 Rs6942067 showed allele-specific luciferase expression and expression quantitative trait loci analysis indicates that it influences expression of DCBLD1, a gene that encodes an unknown membrane protein and is overexpressed in LUAD. human High+Lowthroughput Positional integration of lung adenocarcinoma susceptibility loci with primary human alveolar epithelial cell epigenomes. 是 rs6942067 Lung adenocarcinoma, autoimmune disease, Alzheimer's disease, diabetes, breast, prostate and colon cancer epithelial cell of alveolus of lung E_01_0724 ChIP-seq,FAIRE-seq, qPCR Rs6942067 showed allele-specific luciferase expression and expression quantitative trait loci analysis indicates that it influences expression of DCBLD1, a gene that encodes an unknown membrane protein and is overexpressed in LUAD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Rs6942067 showed allele-specific luciferase expression and expression quantitative trait loci analysis indicates that it influences expression of DCBLD1, a gene that encodes an unknown membrane protein and is overexpressed in LUAD. Immunohistochemical staining Rs6942067 showed allele-specific luciferase expression and expression quantitative trait loci analysis indicates that it influences expression of DCBLD1, a gene that encodes an unknown membrane protein and is overexpressed in LUAD. ChIP-seq,FAIRE-seq, qPCR DCBLD1 Rs6942067 showed allele-specific luciferase expression and expression quantitative trait loci analysis indicates that it influences expression of DCBLD1, a gene that encodes an unknown membrane protein and is overexpressed in LUAD. 30205135 chr17 82075582 82077582 FASN Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Furthermore, we found that blocking Akt signaling through kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2- overexpressing cancer cells. human High+Lowthroughput Kahweol inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2-overexpressing cancer cells 否 mammary cancer breast cancer cell E_01_0725 qRT-PCR,weston blot Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Furthermore, we found that blocking Akt signaling through kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2- overexpressing cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Furthermore, we found that blocking Akt signaling through kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2- overexpressing cancer cells. Immunohistochemical staining Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Furthermore, we found that blocking Akt signaling through kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2- overexpressing cancer cells. qRT-PCR,weston blot FASN Kahweol preferentially inhibited cell proliferation and induced cell death through the induction of a caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines. Furthermore, we found that blocking Akt signaling through kahweol treatment significantly reduced FASN expression and subsequently suppressed cell proliferation in HER2- overexpressing cancer cells. 30201991 chr3 119521370 119523370 CD80 For example, CTLA-4 can inhibit T cell activation intrinsically by outcompeting CD28 for binding to CD80 and CD86, while PD-1 engagement by PD-L1 or PD-L2 triggers an inhibitory signal. human High+Lowthroughput An immunoregulatory and tissue-residency program modulated by c-MAF in human T(H)17 cells 否 chronic inflammation E_01_0726 RNA SEQ, chip SEQ, qPCR, chip qPCR, flow cytometry For example, CTLA-4 can inhibit T cell activation intrinsically by outcompeting CD28 for binding to CD80 and CD86, while PD-1 engagement by PD-L1 or PD-L2 triggers an inhibitory signal. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For example, CTLA-4 can inhibit T cell activation intrinsically by outcompeting CD28 for binding to CD80 and CD86, while PD-1 engagement by PD-L1 or PD-L2 triggers an inhibitory signal. Immunohistochemical staining For example, CTLA-4 can inhibit T cell activation intrinsically by outcompeting CD28 for binding to CD80 and CD86, while PD-1 engagement by PD-L1 or PD-L2 triggers an inhibitory signal. RNA-seq,ChIP-seq,qPCR, ChIP-qPCR,流式细胞术 CD80,CD86 For example, CTLA-4 can inhibit T cell activation intrinsically by outcompeting CD28 for binding to CD80 and CD86, while PD-1 engagement by PD-L1 or PD-L2 triggers an inhibitory signal. ;For example, CTLA-4 can inhibit T cell activation intrinsically by outcompeting CD28 for binding to CD80 and CD86, while PD-1 engagement by PD-L1 or PD-L2 triggers an inhibitory signal. 30195778 chr1 156460686 156462686 MEF2D This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. human Gastric cancer High+Lowthroughput The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric Cancer by Targeting miR-422a 否 gastric cancer gastric cancer cell E_01_0727 Real time qPCR, Weston blot, immunofluorescence staining, gene knockdown This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. Immunohistochemical staining This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. real-time qPCR,weston blot,免疫荧光染色,基因敲降 MEF2D This indicates that lncR-D63785 acts as a competitive endogenous RNA (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent suppression of MEF2D. 30194633 chr18 59217178 59219178 GRP At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. human High+Lowthroughput Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy 否 Saos-2 cell E_01_0728 Flow cytometry, Weston blot, statistical analysis, mcherry-gfp-lc3 analysis, and immunofluorescence light staining At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. Immunohistochemical staining At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. 流式细胞术,weston blot,统计分析,mCherry-GFP-LC3 analysis,免疫荧光光染色 GRP,BAX At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux.;At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. 30193323 chrX 48518970 48520970 EBP The adipogenesis-related downstream mediators of the PI3K/ AKT cascade, that is, forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also were measured by Western blotting. After adipogenic differentiation and idelalisib treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator c (PPARc) and CCAAT-enhancer binding proteins (C/EBP) a/b were determined by Western blot analyses. human High+Lowthroughput Inhibitory Effect of Idelalisib, a Selective Phosphatidylinositol 3-Kinase δ Inhibitor, on Adipogenesis in an In Vitro Model of Graves' Orbitopathy 否 Graves ophthalmopathy (go), graphene oxide fibroblast E_01_0729 Weston blot, ELISA, Western blot The adipogenesis-related downstream mediators of the PI3K/ AKT cascade, that is, forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also were measured by Western blotting. After adipogenic differentiation and idelalisib treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator c (PPARc) and CCAAT-enhancer binding proteins (C/EBP) a/b were determined by Western blot analyses. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The adipogenesis-related downstream mediators of the PI3K/ AKT cascade, that is, forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also were measured by Western blotting. After adipogenic differentiation and idelalisib treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator c (PPARc) and CCAAT-enhancer binding proteins (C/EBP) a/b were determined by Western blot analyses. Immunohistochemical staining The adipogenesis-related downstream mediators of the PI3K/ AKT cascade, that is, forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also were measured by Western blotting. After adipogenic differentiation and idelalisib treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator c (PPARc) and CCAAT-enhancer binding proteins (C/EBP) a/b were determined by Western blot analyses. weston blot,酶联免疫吸附法,免疫印迹法 EBP The adipogenesis-related downstream mediators of the PI3K/ AKT cascade, that is, forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also were measured by Western blotting. After adipogenic differentiation and idelalisib treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator c (PPARc) and CCAAT-enhancer binding proteins (C/EBP) a/b were determined by Western blot analyses. 30191958 chr16 30955149 30957149 SETD1A The histone H3 lysine 4-specific methyltransferase SETD1A is associated with transcription activation and is considered a key epigenetic regulator that modulates the cell cycle and metastasis in triple-negative breast cancer cells. human Mammary High+Lowthroughput Aberrant expression of SETD1A promotes survival and migration of estrogen receptor α-positive breast cancer cells 否 mammary cancer MCF-7 cell E_01_0730 RT qPCR, faire qPCR, mRNA SEQ, RNA SEQ, Weston BOT, gene knockdown The histone H3 lysine 4-specific methyltransferase SETD1A is associated with transcription activation and is considered a key epigenetic regulator that modulates the cell cycle and metastasis in triple-negative breast cancer cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The histone H3 lysine 4-specific methyltransferase SETD1A is associated with transcription activation and is considered a key epigenetic regulator that modulates the cell cycle and metastasis in triple-negative breast cancer cells. Immunohistochemical staining The histone H3 lysine 4-specific methyltransferase SETD1A is associated with transcription activation and is considered a key epigenetic regulator that modulates the cell cycle and metastasis in triple-negative breast cancer cells. RT-qPCR, FAIRE-qPCR,mRNA-seq,RNA-seq,weston bot,基因敲降 SETD1A The histone H3 lysine 4-specific methyltransferase SETD1A is associated with transcription activation and is considered a key epigenetic regulator that modulates the cell cycle and metastasis in triple-negative breast cancer cells. 30190462 chr3 189628438 189630438 TP63 Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. human High+Lowthroughput Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression 否 Squamous cell carcinomas (SCCs) squamous cell E_01_0731 qRT-PCR,weston blot,RNA-seq,plasmid transfection,ChIP-seq Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. Immunohistochemical staining Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. qRT-PCR,weston blot,RNA-seq,plasmid transfection,ChIP-seq TP63,SOX2,EGFR Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. ;Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. ;Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter.Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. 30190126 chr17 49596074 49598074 SPOP Notably, SPOP inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD. human High+Lowthroughput SPOP promotes FADD degradation and inhibits NF-κB activity in non-small cell lung cancer 否 Non small cell lung cancer NSCLC cell E_01_0732 Statistical analysis, Weston blot, RT qPCR Notably, SPOP inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Notably, SPOP inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD. Immunohistochemical staining Notably, SPOP inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD. 统计分析,weston blot,RT-qPCR SPOP,FADD Notably, SPOP inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD. ; Notably, SPOP inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD. 30185787 chr6 124838963 124840963 Cd4 An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; mouse High+Lowthroughput Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene 否 T cell E_01_0733 ATAC SEQ, chip SEQ, chip qPCR, quantitative RT-PCR, flow cytometry An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; Immunohistochemical staining An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; ATAC-Seq,ChIP-Seq,ChIP-qPCR ,Quantitative RT-PCR,流式细胞术 Cd4 An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for the helper-lineage-specific expression of CD4; 30182035 chr2 60447469 60449469 BCL11A In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with b-thalassemia major resulted in a readily detectable g-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. human High+Lowthroughput Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in Erythroid Cells of Patients with β-Thalassemia Major 否 B-globin thalassemia progenitor cell E_01_0734 Miseq deep sequencing, QRT PCR, immunofluorescence staining In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with b-thalassemia major resulted in a readily detectable g-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with b-thalassemia major resulted in a readily detectable g-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. Immunohistochemical staining In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with b-thalassemia major resulted in a readily detectable g-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. MiSeq Deep Sequencing,qRT-PCR,免疫荧光染色 BCL11A In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with b-thalassemia major resulted in a readily detectable g-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. 30176898 chr22 39517104 39519104 ATF4 Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. human High+Lowthroughput Corosolic acid, a natural triterpenoid, induces ER stress-dependent apoptosis in human castration resistant prostate cancer cells via activation of IRE-1/JNK, PERK/CHOP and TRIB3 否 Prostate cancer (CRPC) E_01_0735 Real time PCR, Western blot, immunofluorescence light staining, gene transfection, statistical analysis, MTT assay, flow cytometry Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. Immunohistochemical staining Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. Real-time PCR,western blot,免疫荧光光染色,基因转染,统计分析,MTT法,流式细胞术 TRIB3 ATF4 Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. 30174670 chr20 38343789 38345789 LBP LBP can raise both from IVD-induced damage of dorsal root ganglions (DRG) and from nociceptive stimulation of DRGs by molecules released from the degenerated IVD (7 9). Indeed, severity of DDD correlates with increased expression of inflammation mediators/markers in the IVD tissue (10), including interleukin-1 beta (IL-1β) (11), tumor necrosis factor-alpha (TNF-α) (12), interleukin-6 (IL-6), and interleukin-8 (IL-8) (13). human High+Lowthroughput p38 MAPK Facilitates Crosstalk Between Endoplasmic Reticulum Stress and IL-6 Release in the Intervertebral Disc 否 Degenerative disc disease, inflammation, neurodegenerative disease, type 2 diabetes, rheumatoid arthritis E_01_0736 Enzyme-Linked Immunosorbent Assay,Metabolic Activity Assay (MTT),RT-qPCR LBP can raise both from IVD-induced damage of dorsal root ganglions (DRG) and from nociceptive stimulation of DRGs by molecules released from the degenerated IVD (7 9). Indeed, severity of DDD correlates with increased expression of inflammation mediators/markers in the IVD tissue (10), including interleukin-1 beta (IL-1β) (11), tumor necrosis factor-alpha (TNF-α) (12), interleukin-6 (IL-6), and interleukin-8 (IL-8) (13). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LBP can raise both from IVD-induced damage of dorsal root ganglions (DRG) and from nociceptive stimulation of DRGs by molecules released from the degenerated IVD (7 9). Indeed, severity of DDD correlates with increased expression of inflammation mediators/markers in the IVD tissue (10), including interleukin-1 beta (IL-1β) (11), tumor necrosis factor-alpha (TNF-α) (12), interleukin-6 (IL-6), and interleukin-8 (IL-8) (13). Immunohistochemical staining LBP can raise both from IVD-induced damage of dorsal root ganglions (DRG) and from nociceptive stimulation of DRGs by molecules released from the degenerated IVD (7 9). Indeed, severity of DDD correlates with increased expression of inflammation mediators/markers in the IVD tissue (10), including interleukin-1 beta (IL-1β) (11), tumor necrosis factor-alpha (TNF-α) (12), interleukin-6 (IL-6), and interleukin-8 (IL-8) (13). Enzyme-Linked Immunosorbent Assay,Metabolic Activity Assay (MTT),RT-qPCR LBP,IVD LBP can raise both from IVD-induced damage of dorsal root ganglions (DRG) and from nociceptive stimulation of DRGs by molecules released from the degenerated IVD (7 9). Indeed, severity of DDD correlates with increased expression of inflammation mediators/markers in the IVD tissue (10), including interleukin-1 beta (IL-1β) (11), tumor necrosis factor-alpha (TNF-α) (12), interleukin-6 (IL-6), and interleukin-8 (IL-8) (13).;LBP can raise both from IVD-induced damage of dorsal root ganglions (DRG) and from nociceptive stimulation of DRGs by molecules released from the degenerated IVD (7 9). Indeed, severity of DDD correlates with increased expression of inflammation mediators/markers in the IVD tissue (10), including interleukin-1 beta (IL-1β) (11), tumor necrosis factor-alpha (TNF-α) (12), interleukin-6 (IL-6), and interleukin-8 (IL-8) (13). 30172905 chr19 5555467 5557467 TINCR As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. human adipose High+Lowthroughput LncRNA TINCR/miR-31-5p/C/EBP-α feedback loop modulates the adipogenic differentiation process in human adipose tissue-derived mesenchymal stem cells 否 Obesity mesenchymal stem cell E_01_0737 Real-time PC,RNA Immunoprecipitation (RIP), Chromatin immunoprecipitation (ChIP),weston blot As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. Immunohistochemical staining As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. Real-time PC,RNA Immunoprecipitation (RIP), Chromatin immunoprecipitation (ChIP),weston blot TINCR As we know, Terminal differentiation-induced ncRNA (TINCR) is required in somatic tissue differentiation. 30170702 chr9 81580913 81582913 TLE1 5 Recently, IHC labelling for the transducin-like enhancer of split 1 (TLE1) has been proposed as a marker for diagnosis of synovial sarcoma. human High+Lowthroughput Pleural malignant mesothelioma versus pleuropulmonary synovial sarcoma: a clinicopathological study of 22 cases with molecular analysis and survival data 否 Malignant neoplasm, spindle cell carcinoma of the lung E_01_0738 RT-PCR, immunofluorescence light staining, fluorescence in situ hybridization (FISH) 5 Recently, IHC labelling for the transducin-like enhancer of split 1 (TLE1) has been proposed as a marker for diagnosis of synovial sarcoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq 5 Recently, IHC labelling for the transducin-like enhancer of split 1 (TLE1) has been proposed as a marker for diagnosis of synovial sarcoma. Immunohistochemical staining 5 Recently, IHC labelling for the transducin-like enhancer of split 1 (TLE1) has been proposed as a marker for diagnosis of synovial sarcoma. RT-PCR,免疫荧光光染色,荧光原位杂交(FISH) TLE1 5 Recently, IHC labelling for the transducin-like enhancer of split 1 (TLE1) has been proposed as a marker for diagnosis of synovial sarcoma. 30168706 chr5 102751294 102753294 PAM In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. human High+Lowthroughput Fenoprofen-An Old Drug Rediscovered as a Biased Allosteric Enhancer for Melanocortin Receptors 否 Obesity, chronic inflammation pigment cell E_01_0739 Western blot, statistical analysis In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. Immunohistochemical staining In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. western blot,统计分析 MC1R MYCBP2,MC2R In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. Extensive studies spanning87 decades have elucidated well-established functions of melanocortins mediated by cell88 surface receptors named MC1R (MSH receptor), MC2R (ACTH receptor), MC3R and89 MC4R (neural MCRs), and MC5R 7, 8. In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. ;In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively31 activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen32 stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively33 among this highly conserved family of receptors. Moreover, PAM activity and biased34 signaling induced by fenoprofen were observed not only at wild-type but also at35 naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer36 action might constitute as novel therapeutic opportunity for obese patients harboring37 these mutations. Extensive studies spanning87 decades have elucidated well-established functions of melanocortins mediated by cell88 surface receptors named MC1R (MSH receptor), MC2R (ACTH receptor), MC3R and89 MC4R (neural MCRs), and MC5R 7, 8. 30165902 chr13 109749894 109751894 IRS2 hMSCs were transfected by miR-431 or small interfering RNA (siRNA) for insulin receptor substance 2 (IRS2). human High+Lowthroughput miR-431 inhibits adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via targeting insulin receptor substance 2 否 Type 2 diabetes, adipocyte cancer mesenchymal stem cell E_01_0740 qRT-PCR,weston blot hMSCs were transfected by miR-431 or small interfering RNA (siRNA) for insulin receptor substance 2 (IRS2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq hMSCs were transfected by miR-431 or small interfering RNA (siRNA) for insulin receptor substance 2 (IRS2). Immunohistochemical staining hMSCs were transfected by miR-431 or small interfering RNA (siRNA) for insulin receptor substance 2 (IRS2). qRT-PCR,weston blot IRS2 hMSCs were transfected by miR-431 or small interfering RNA (siRNA) for insulin receptor substance 2 (IRS2). 30161129 chr3 123607146 123609146 MYLK We previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. human High+Lowthroughput Single nucleotide polymorphisms in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans 是 Colon cancer, lung cancer Colon cell E_01_0741 MYLKP1 luciferase assay,PCR differential detection We previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. Immunohistochemical staining We previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. MYLKP1 luciferase assay,PCR differential detection MYLK We previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. 30157915 chr3 133743588 133745588 TF Pairwise comparisons between cell lines demonstrate a strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. human High+Lowthroughput Genomic meta-analysis of the interplay between 3D chromatin organization and gene expression programs under basal and stress conditions 否 mammary cancer stem cell E_01_0742 Chip SEQ, RNA SEQ, flow cytometry Pairwise comparisons between cell lines demonstrate a strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Pairwise comparisons between cell lines demonstrate a strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. Immunohistochemical staining Pairwise comparisons between cell lines demonstrate a strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. ChIP-seq,RNA-seq,流式细胞术 TF Pairwise comparisons between cell lines demonstrate a strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. 30157244 chr6 137489826 137491826 OLIG3 OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes. human High+Lowthroughput Whole exome sequencing in Finnish families identifies new candidate genes for osteoarthritis 是 Osteoarthritis (OA) GM12878 cell E_01_0743 Whole exome sequencing,PCR OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes. Immunohistochemical staining OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes. Whole exome sequencing,PCR OLIG3,FIP1L1 OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes.;OLIG3 and FIP1L1 have specific roles in transcription and may effect expression of other genes. 30154449 chr12 53959572 53961572 HOTAIR Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. We recently demonstrated that HOTAIR expression is induced in hepatocytes undergoing EMT and functions to bridge, in specific chromatin sites, the interaction between EZH2 and Snail. In other words, the EMT master factor Snail (i.e., sufficient to trigger and orchestrate the transition) conveys the Polycomb catalytic subunit to specific sites by means of a direct interaction with HOTAIR. human High+Lowthroughput The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation 否 Gastrointestinal cancer, hepatocellular carcinoma epithelial cell E_01_0744 RT qPCR, chromatin immunoprecipitation (chip) analysis, statistical analysis, Weston blot Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. We recently demonstrated that HOTAIR expression is induced in hepatocytes undergoing EMT and functions to bridge, in specific chromatin sites, the interaction between EZH2 and Snail. In other words, the EMT master factor Snail (i.e., sufficient to trigger and orchestrate the transition) conveys the Polycomb catalytic subunit to specific sites by means of a direct interaction with HOTAIR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. We recently demonstrated that HOTAIR expression is induced in hepatocytes undergoing EMT and functions to bridge, in specific chromatin sites, the interaction between EZH2 and Snail. In other words, the EMT master factor Snail (i.e., sufficient to trigger and orchestrate the transition) conveys the Polycomb catalytic subunit to specific sites by means of a direct interaction with HOTAIR. Immunohistochemical staining Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. We recently demonstrated that HOTAIR expression is induced in hepatocytes undergoing EMT and functions to bridge, in specific chromatin sites, the interaction between EZH2 and Snail. In other words, the EMT master factor Snail (i.e., sufficient to trigger and orchestrate the transition) conveys the Polycomb catalytic subunit to specific sites by means of a direct interaction with HOTAIR. RT-qPCR,Chromatin immunoprecipitation (ChIP) analysis,统计分析,weston blot HOTAIR,EZH2 Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. We recently demonstrated that HOTAIR expression is induced in hepatocytes undergoing EMT and functions to bridge, in specific chromatin sites, the interaction between EZH2 and Snail. In other words, the EMT master factor Snail (i.e., sufficient to trigger and orchestrate the transition) conveys the Polycomb catalytic subunit to specific sites by means of a direct interaction with HOTAIR.;Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. We recently demonstrated that HOTAIR expression is induced in hepatocytes undergoing EMT and functions to bridge, in specific chromatin sites, the interaction between EZH2 and Snail. In other words, the EMT master factor Snail (i.e., sufficient to trigger and orchestrate the transition) conveys the Polycomb catalytic subunit to specific sites by means of a direct interaction with HOTAIR. 30150754 chr16 67559736 67561736 CTCF Examination of chromatin interaction around functional elements such as promoters and CTCF binding sites within 2000 bp regions at a 10-bp resolution revealed a clear pattern of separation of interaction domains anchored at promoters of actively transcribed genes and at CTCF binding sites (Fig. 2c). human High+Lowthroughput Trac-looping measures genome structure and chromatin accessibility 否 CD4+T cell E_01_0745 ATAC-seq,PCR,3D fluorescence in situ hybridization (FISH) Examination of chromatin interaction around functional elements such as promoters and CTCF binding sites within 2000 bp regions at a 10-bp resolution revealed a clear pattern of separation of interaction domains anchored at promoters of actively transcribed genes and at CTCF binding sites (Fig. 2c). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Examination of chromatin interaction around functional elements such as promoters and CTCF binding sites within 2000 bp regions at a 10-bp resolution revealed a clear pattern of separation of interaction domains anchored at promoters of actively transcribed genes and at CTCF binding sites (Fig. 2c). Immunohistochemical staining Examination of chromatin interaction around functional elements such as promoters and CTCF binding sites within 2000 bp regions at a 10-bp resolution revealed a clear pattern of separation of interaction domains anchored at promoters of actively transcribed genes and at CTCF binding sites (Fig. 2c). ATAC-seq,PCR,3D fluorescence in situ hybridization (FISH) CTCF Examination of chromatin interaction around functional elements such as promoters and CTCF binding sites within 2000 bp regions at a 10-bp resolution revealed a clear pattern of separation of interaction domains anchored at promoters of actively transcribed genes and at CTCF binding sites (Fig. 2c). 30150059 chr7 148804095 148806095 EZH2 Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70 90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression. human High+Lowthroughput Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/β-catenin signaling 否 Hepatocellular carcinoma (HCC) LO2 cell E_01_0746 Quantitative RT-PCR, chromatin immunoprecipitation, immunoblotting, gene knockdown, Weston blot Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70 90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70 90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70 90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression. Quantitative RT-PCR,染色质免疫沉淀,免疫印迹法,基因敲降,weston blot EZH2 Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70 90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression. 30145643 chr1 161763665 161765665 ATF6 The UPR is mediated by three main sensors embedded in the ER membrane Activating transcription factor 6 (ATF6), Inositol-requiring enzyme 1 (IRE1) and Protein Kinase R-like ER kinase (PERK) [3]. Activated IRE1 splices an intron from XBP1 mRNA allowing it to be translated into a functional transcription factor (XBP1s), which has several downstream targets involved in the UPR [11,12]. human High+Lowthroughput GIV/Girdin promotes cell survival during endoplasmic reticulum stress 否 Cancer, diabetes E_01_0747 Weston blot, statistical analysis The UPR is mediated by three main sensors embedded in the ER membrane Activating transcription factor 6 (ATF6), Inositol-requiring enzyme 1 (IRE1) and Protein Kinase R-like ER kinase (PERK) [3]. Activated IRE1 splices an intron from XBP1 mRNA allowing it to be translated into a functional transcription factor (XBP1s), which has several downstream targets involved in the UPR [11,12]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The UPR is mediated by three main sensors embedded in the ER membrane Activating transcription factor 6 (ATF6), Inositol-requiring enzyme 1 (IRE1) and Protein Kinase R-like ER kinase (PERK) [3]. Activated IRE1 splices an intron from XBP1 mRNA allowing it to be translated into a functional transcription factor (XBP1s), which has several downstream targets involved in the UPR [11,12]. Immunohistochemical staining The UPR is mediated by three main sensors embedded in the ER membrane Activating transcription factor 6 (ATF6), Inositol-requiring enzyme 1 (IRE1) and Protein Kinase R-like ER kinase (PERK) [3]. Activated IRE1 splices an intron from XBP1 mRNA allowing it to be translated into a functional transcription factor (XBP1s), which has several downstream targets involved in the UPR [11,12]. weston blot,统计分析 ATF6,XBP1 The UPR is mediated by three main sensors embedded in the ER membrane Activating transcription factor 6 (ATF6), Inositol-requiring enzyme 1 (IRE1) and Protein Kinase R-like ER kinase (PERK) [3]. Activated IRE1 splices an intron from XBP1 mRNA allowing it to be translated into a functional transcription factor (XBP1s), which has several downstream targets involved in the UPR [11,12]. ;The UPR is mediated by three main sensors embedded in the ER membrane Activating transcription factor 6 (ATF6), Inositol-requiring enzyme 1 (IRE1) and Protein Kinase R-like ER kinase (PERK) [3]. Activated IRE1 splices an intron from XBP1 mRNA allowing it to be translated into a functional transcription factor (XBP1s), which has several downstream targets involved in the UPR [11,12]. 30145202 chr6 151653890 151655890 ESR1 Abstract Breast cancer is the most prevalent type of malignancy in women with ~1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand- dependent transcription factor. Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ERα-mediated cell proliferation. human High+Lowthroughput CUEDC1 is a primary target of ERα essential for the growth of breast cancer cells 否 mammary cancer HEK293T E_01_0748 qPCR,weston blot,GRO-seq，DNA-seq,RNA-seq,ChIP-seq Abstract Breast cancer is the most prevalent type of malignancy in women with ~1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand- dependent transcription factor. Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ERα-mediated cell proliferation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Abstract Breast cancer is the most prevalent type of malignancy in women with ~1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand- dependent transcription factor. Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ERα-mediated cell proliferation. Immunohistochemical staining Abstract Breast cancer is the most prevalent type of malignancy in women with ~1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand- dependent transcription factor. Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ERα-mediated cell proliferation. qPCR,weston blot,GRO-seq，DNA-seq,RNA-seq,ChIP-seq CUEDC1 ESR1 Abstract Breast cancer is the most prevalent type of malignancy in women with ~1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand- dependent transcription factor. Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ERα-mediated cell proliferation. Abstract Breast cancer is the most prevalent type of malignancy in women with ~1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand- dependent transcription factor. Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ERα-mediated cell proliferation. 30141986 chr18 47806131 47808131 SMAD2 LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Active CaMKIIδ activates class IIa histone deacetylases (HDACs), HDAC4 and HDAC5, which in turn activate the myocyte enhancer factor 2 (MEF2) transcription factor (3). MEF2 drives the expression of fetal cardiac and stress response genes, including the negative growth factor regulator myostatin (MSTN) (33). human Myocardial High+Lowthroughput Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery 否 heart disease cardiac muscle cell (sensu Arthopoda) E_01_0749 weston blot,RNA sequencing analysis LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Active CaMKIIδ activates class IIa histone deacetylases (HDACs), HDAC4 and HDAC5, which in turn activate the myocyte enhancer factor 2 (MEF2) transcription factor (3). MEF2 drives the expression of fetal cardiac and stress response genes, including the negative growth factor regulator myostatin (MSTN) (33). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Active CaMKIIδ activates class IIa histone deacetylases (HDACs), HDAC4 and HDAC5, which in turn activate the myocyte enhancer factor 2 (MEF2) transcription factor (3). MEF2 drives the expression of fetal cardiac and stress response genes, including the negative growth factor regulator myostatin (MSTN) (33). Immunohistochemical staining LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Active CaMKIIδ activates class IIa histone deacetylases (HDACs), HDAC4 and HDAC5, which in turn activate the myocyte enhancer factor 2 (MEF2) transcription factor (3). MEF2 drives the expression of fetal cardiac and stress response genes, including the negative growth factor regulator myostatin (MSTN) (33). weston blot,RNA sequencing analysis HDAC5 SMAD2 LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Active CaMKIIδ activates class IIa histone deacetylases (HDACs), HDAC4 and HDAC5, which in turn activate the myocyte enhancer factor 2 (MEF2) transcription factor (3). MEF2 drives the expression of fetal cardiac and stress response genes, including the negative growth factor regulator myostatin (MSTN) (33). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Active CaMKIIδ activates class IIa histone deacetylases (HDACs), HDAC4 and HDAC5, which in turn activate the myocyte enhancer factor 2 (MEF2) transcription factor (3). MEF2 drives the expression of fetal cardiac and stress response genes, including the negative growth factor regulator myostatin (MSTN) (33). 30140372 chr1 173855894 173857894 GAS5 The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. human High+Lowthroughput Lyophilized human cells stored at room temperature preserve multiple RNA species at excellent quality for RNA sequencing 否 E_01_0750 RT qPCR, RNA SEQ, statistical analysis The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. Immunohistochemical staining The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. RT-qPCR,RNA-Seq,统计分析 TUG1 GAS5,MALAT1 The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. ;The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (MALAT1, GAS5 and TUG1), were not significantly different between the two groups as assessed by RT-qPCR. 30136421 chr19 10130546 10132546 DNMT1 While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7). human Liver cancer liver High+Lowthroughput Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma 否 Hepatocellular carcinoma (HCC), cirrhosis, hepatitis B hepatocyte E_01_0751 qRT-PCR ,ChIP-seq,RNA-seq While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7). Immunohistochemical staining While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7). qRT-PCR ,ChIP-seq,RNA-seq TET3,TET2 DNMT1,DNMT3A,TET1 While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7).;While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7). While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7).;While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7).;While it is likely that etiologic risk exposures drive HCC through both genetic and epigenetic mechanisms, epigenetic modifications appear to be profoundly disrupted preceding detectable malignancy (5, 6). Epigenetic marks on the DNA, including 5-methylcytosine (5mC, mediated by the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B) and 5-hydroxymethylcytosine (5hmC, mediated by the ten-eleven translocation family TET1, TET2, and TET3), are critical regulators of development that frequently become deregulated in and directly contribute to tumorigenesis (7). 30134807 chr13 30453788 30455788 HMGB1 Background High mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs. human High+Lowthroughput Ligation of free HMGB1 to TLR2 in the absence of ligand is negatively regulated by the C-terminal tail domain 否 inflammation macrophage E_01_0752 Statistical analysis, ELISA method Background High mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Background High mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs. Immunohistochemical staining Background High mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs. 统计分析,elisa法 HMGB1 TLR2 Background High mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs. Background High mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs. 30134174 chr20 47206665 47208665 ZMYND8 Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression. human High+Lowthroughput Positive Regulation of Transcription by Human ZMYND8 through Its Association with P-TEFb Complex 否 293T cell E_01_0753 Chip SEQ, QRT PCR, Weston blot, analysis of immunoprecipitation reactions, statistical analysis Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression. Immunohistochemical staining Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression. ChIP-seq,qRT-PCR,weston blot,免疫沉淀反应分析,统计分析 ZMYND8 KDM5C,CDK9 Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression. Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression.;Physiologically, we further show that the ZMYND8 P-TEFb complex-mediated transcriptional activation is required for All-Trans Retinoic Acid (ATRA)-mediated differentiation of neuronal precursor cells. Through its interaction with KDM5C, ZMYND8 also suppresses enhancer over-expression by maintaining H3K4me1 enhancer signature (Shen et al., 2016). Among all the positive regulators of transcription, human P-TEFb complex, a heterodimer of CyclinT1/T2 and cyclin-dependent kinase 9 (CDK9) (Peng et al., 1998), plays a major role in activating target gene expression. 30132567 chr14 49641316 49643316 POLE2 Furthermore, knockdown of POLE2 expression inhibited A549 and NCI-H1299 cell proliferation and apoptosis. human High+Lowthroughput Knockdown of POLE2 expression suppresses lung adenocarcinoma cell malignant phenotypes in?vitro 否 Lung adenocarcinoma A549 cell E_01_0754 QRT PCR, Weston blot, statistical analysis Furthermore, knockdown of POLE2 expression inhibited A549 and NCI-H1299 cell proliferation and apoptosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, knockdown of POLE2 expression inhibited A549 and NCI-H1299 cell proliferation and apoptosis. Immunohistochemical staining Furthermore, knockdown of POLE2 expression inhibited A549 and NCI-H1299 cell proliferation and apoptosis. qRT-PCR,weston blot,统计分析 POLE2 Furthermore, knockdown of POLE2 expression inhibited A549 and NCI-H1299 cell proliferation and apoptosis. 30127913 chr1 212033036 212035036 DTL The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC. human High+Lowthroughput Potential biomarkers of HCC based on gene expression and DNA methylation profiles 否 Hepatocellular carcinoma endothelial cell E_01_0755 RT qPCR, statistical analysis The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC. Immunohistochemical staining The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC. RT-qPCR,统计分析 DTL,DUSP1,SOCS2 NFKBIA The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC.;The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC.;The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC. The present study suggested that DTL, DUSP1, NFKBIA and SOCS2 may be potential biomarkers of HCC, and the tumor protein p53 signaling , forkhead box O1 signaling and metabolic pathways may serve roles in the pathogenesis of HCC. 30127433 chr16 67559500 67561500 CTCF Go to: Introduction Cohesin is a multiprotein complex that cooperates with the sequence-specific DNA binding protein CTCF in forming key features of 3D genome organization such as topologically associated domains (TADs), contact domains and chromatin loops. human High+Lowthroughput Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation 否 Acute myeloid leukemia macrophage E_01_0756 RT-PCR,ChIP-PCR,RNA-seq,FACS analysis,GRO-seq,ATAC-seq,ChIP-seq Go to: Introduction Cohesin is a multiprotein complex that cooperates with the sequence-specific DNA binding protein CTCF in forming key features of 3D genome organization such as topologically associated domains (TADs), contact domains and chromatin loops. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Go to: Introduction Cohesin is a multiprotein complex that cooperates with the sequence-specific DNA binding protein CTCF in forming key features of 3D genome organization such as topologically associated domains (TADs), contact domains and chromatin loops. Immunohistochemical staining Go to: Introduction Cohesin is a multiprotein complex that cooperates with the sequence-specific DNA binding protein CTCF in forming key features of 3D genome organization such as topologically associated domains (TADs), contact domains and chromatin loops. RT-PCR,ChIP-PCR,RNA-seq,FACS analysis,GRO-seq,ATAC-seq,ChIP-seq CTCF Go to: Introduction Cohesin is a multiprotein complex that cooperates with the sequence-specific DNA binding protein CTCF in forming key features of 3D genome organization such as topologically associated domains (TADs), contact domains and chromatin loops. 30123075 chr11 73215337 73217337 P2RY2 P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. human High+Lowthroughput Enhancer RNA - P2RY2e induced by estrogen promotes malignant behaviors of bladder cancer 否 Breast, bladder, stomach, pancreas, prostate, lung T24 cell E_01_0757 RT qPCR, flow cytometry, ELISA, statistical analysis P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. Immunohistochemical staining P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. RT-qPCR,流式细胞术,ELISA,统计分析 P2RY2 P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. 30121393 chr12 102954801 102956801 ASCL1 ABSTRACT Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete- scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung can- cer and large cell neuroendocrine carcinoma. human High+Lowthroughput An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas 否 Lung adenocarcinoma, lung squamous cell carcinoma tumor cell E_01_0758 RNA-seq,RT-PCR ABSTRACT Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete- scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung can- cer and large cell neuroendocrine carcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ABSTRACT Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete- scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung can- cer and large cell neuroendocrine carcinoma. Immunohistochemical staining ABSTRACT Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete- scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung can- cer and large cell neuroendocrine carcinoma. RNA-seq,RT-PCR ASCL1 ABSTRACT Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete- scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung can- cer and large cell neuroendocrine carcinoma. 30119259 chr7 148804464 148806464 EZH2 Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through re- cruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. MALAT1 human High+Lowthroughput Long noncoding RNA HOXD-AS1 aggravates osteosarcoma carcinogenesis through epigenetically inhibiting p57 via EZH2 否 Osteosarcoma osteosarcoma cell E_01_0759 RT-PCR, Weston blot, statistical analysis Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through re- cruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. MALAT1 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through re- cruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. MALAT1 Immunohistochemical staining Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through re- cruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. MALAT1 RT-PCR,weston blot,统计分析 EZH2,MALAT1 Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through re- cruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. MALAT1;Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through re- cruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. MALAT1 30118678 chr11 67116871 67118871 KDM2A Surprisingly, these basally-active estrogen-repressed (BAER) enhancers are decommissioned by ERα-dependent recruitment of the histone demethylase, KDM2A, functioning independently of its demethylase activity. While indirectly bound ERα recruits coactivators to these enhancers in a ligand-dependent fashion, the repression events, unexpectedly, reflect the availability of the ERα DNA binding domain (DBD) to interact with the histone demethylase, KDM2A, which, even in the absence of its demethylase function, serves to recruit the ubiquitin ligase NEDD4 to these enhancers, resulting ubiquitylation and dismissal of Pol II and consequent inhibition of these enhancer activities. human High+Lowthroughput Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program 否 mammary cancer MCF7 cell E_01_0760 RT-qPCR,GRO-seq,ChIP-seq,ChIP-qPCR ,weston blot,PRO-seq Surprisingly, these basally-active estrogen-repressed (BAER) enhancers are decommissioned by ERα-dependent recruitment of the histone demethylase, KDM2A, functioning independently of its demethylase activity. While indirectly bound ERα recruits coactivators to these enhancers in a ligand-dependent fashion, the repression events, unexpectedly, reflect the availability of the ERα DNA binding domain (DBD) to interact with the histone demethylase, KDM2A, which, even in the absence of its demethylase function, serves to recruit the ubiquitin ligase NEDD4 to these enhancers, resulting ubiquitylation and dismissal of Pol II and consequent inhibition of these enhancer activities. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Surprisingly, these basally-active estrogen-repressed (BAER) enhancers are decommissioned by ERα-dependent recruitment of the histone demethylase, KDM2A, functioning independently of its demethylase activity. While indirectly bound ERα recruits coactivators to these enhancers in a ligand-dependent fashion, the repression events, unexpectedly, reflect the availability of the ERα DNA binding domain (DBD) to interact with the histone demethylase, KDM2A, which, even in the absence of its demethylase function, serves to recruit the ubiquitin ligase NEDD4 to these enhancers, resulting ubiquitylation and dismissal of Pol II and consequent inhibition of these enhancer activities. Immunohistochemical staining Surprisingly, these basally-active estrogen-repressed (BAER) enhancers are decommissioned by ERα-dependent recruitment of the histone demethylase, KDM2A, functioning independently of its demethylase activity. While indirectly bound ERα recruits coactivators to these enhancers in a ligand-dependent fashion, the repression events, unexpectedly, reflect the availability of the ERα DNA binding domain (DBD) to interact with the histone demethylase, KDM2A, which, even in the absence of its demethylase function, serves to recruit the ubiquitin ligase NEDD4 to these enhancers, resulting ubiquitylation and dismissal of Pol II and consequent inhibition of these enhancer activities. RT-qPCR,GRO-seq,ChIP-seq,ChIP-qPCR ,weston blot,PRO-seq KDM2A Surprisingly, these basally-active estrogen-repressed (BAER) enhancers are decommissioned by ERα-dependent recruitment of the histone demethylase, KDM2A, functioning independently of its demethylase activity. While indirectly bound ERα recruits coactivators to these enhancers in a ligand-dependent fashion, the repression events, unexpectedly, reflect the availability of the ERα DNA binding domain (DBD) to interact with the histone demethylase, KDM2A, which, even in the absence of its demethylase function, serves to recruit the ubiquitin ligase NEDD4 to these enhancers, resulting ubiquitylation and dismissal of Pol II and consequent inhibition of these enhancer activities. 30116320 chr7 45108174 45110174 Bax The results revealed that baicalin administration increased cell viability and decreased LDH levels, most notably at a dosage of 100 mol/l. Baicalin pretreatment also downregulated the expression of caspase 3, cleaved caspase 3 and Bax, while upregulating the expression of Bcl-2. mouse High+Lowthroughput Baicalin attenuates liver hypoxia/reoxygenation injury by inducing autophagy 否 B cell lymphoma LO2 cell E_01_0761 RT qPCR, Weston blot, statistical analysis, flow cytometry The results revealed that baicalin administration increased cell viability and decreased LDH levels, most notably at a dosage of 100 mol/l. Baicalin pretreatment also downregulated the expression of caspase 3, cleaved caspase 3 and Bax, while upregulating the expression of Bcl-2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results revealed that baicalin administration increased cell viability and decreased LDH levels, most notably at a dosage of 100 mol/l. Baicalin pretreatment also downregulated the expression of caspase 3, cleaved caspase 3 and Bax, while upregulating the expression of Bcl-2. Immunohistochemical staining The results revealed that baicalin administration increased cell viability and decreased LDH levels, most notably at a dosage of 100 mol/l. Baicalin pretreatment also downregulated the expression of caspase 3, cleaved caspase 3 and Bax, while upregulating the expression of Bcl-2. RT-qPCR,weston blot,统计分析,流式细胞术 Bax The results revealed that baicalin administration increased cell viability and decreased LDH levels, most notably at a dosage of 100 mol/l. Baicalin pretreatment also downregulated the expression of caspase 3, cleaved caspase 3 and Bax, while upregulating the expression of Bcl-2. 30108282 chr9 21999744 22001744 CDKN2B Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA 1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis, and several forms of cancer. Direct binding of CDKN2B-AS1 transcripts to RBMS1 was shown by RNA immunoprecipitation. RBMS1 encodes a cell cycle suppressor. human High+Lowthroughput Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer binding factor RBMS1 是 rs564398,rs10811661,rs7593730,rs10217586 Type 2 diabetes (T2D), atherosclerosis, coronary heart disease T-Rex HEK293 cell E_01_0762 weston blot,qRT-PCR,RNA immunoprecipitation (RIP), RNA-seq Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA 1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis, and several forms of cancer. Direct binding of CDKN2B-AS1 transcripts to RBMS1 was shown by RNA immunoprecipitation. RBMS1 encodes a cell cycle suppressor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA 1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis, and several forms of cancer. Direct binding of CDKN2B-AS1 transcripts to RBMS1 was shown by RNA immunoprecipitation. RBMS1 encodes a cell cycle suppressor. Immunohistochemical staining Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA 1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis, and several forms of cancer. Direct binding of CDKN2B-AS1 transcripts to RBMS1 was shown by RNA immunoprecipitation. RBMS1 encodes a cell cycle suppressor. weston blot,qRT-PCR,RNA immunoprecipitation (RIP), RNA-seq CDKN2B Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA 1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis, and several forms of cancer. Direct binding of CDKN2B-AS1 transcripts to RBMS1 was shown by RNA immunoprecipitation. RBMS1 encodes a cell cycle suppressor. 30105866 chr17 48721960 48723960 HOXB13 Conversely, knockdown of HOXB13 AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13 AS1 overexpression increased DNMT3B mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. human High+Lowthroughput Long noncoding RNA HOXB13-AS1 regulates HOXB13 gene methylation by interacting with EZH2 in glioma 否 Glioma, breast cancer Glioma cell E_01_0763 QRT – PCR, chromatin immunoprecipitation (chip) assay, Weston blot, statistical analysis, gene knockdown Conversely, knockdown of HOXB13 AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13 AS1 overexpression increased DNMT3B mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conversely, knockdown of HOXB13 AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13 AS1 overexpression increased DNMT3B mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. Immunohistochemical staining Conversely, knockdown of HOXB13 AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13 AS1 overexpression increased DNMT3B mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. qRT–PCR,染色质免疫沉淀(ChIP)测定,weston blot,统计分析,基因敲降 HOXB13,EZH2 Conversely, knockdown of HOXB13 AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13 AS1 overexpression increased DNMT3B mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. ;Conversely, knockdown of HOXB13 AS1 resulted in decreased cell proliferation and tumor growth. Mechanistically, we showed that HOXB13 AS1 overexpression increased DNMT3B mediated methylation of adjacent gene HOXB13 promoter by binding with the enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP), epigenetically suppressing HOXB13 expression. 30104406 chr3 108955128 108957128 MORC1 We previously demonstrated that the Su(var)3 9 homologs SUVH2 and SUVH9, which are RdDM components, interact with MORC1 and MORC6 and thereby link the RdDM pathway and heterochromatin condensation (Liu et al, 2016). However, it is thought that the RdDM pathway is unlikely to be involved in heterochromatin condensation at the whole genome level. human High+Lowthroughput The PEAT protein complexes are required for histone deacetylation and heterochromatin silencing 否 E_01_0764 ChIP‐seq,RNA expression analysis,Immunofluorescence assay,,weston blot We previously demonstrated that the Su(var)3 9 homologs SUVH2 and SUVH9, which are RdDM components, interact with MORC1 and MORC6 and thereby link the RdDM pathway and heterochromatin condensation (Liu et al, 2016). However, it is thought that the RdDM pathway is unlikely to be involved in heterochromatin condensation at the whole genome level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We previously demonstrated that the Su(var)3 9 homologs SUVH2 and SUVH9, which are RdDM components, interact with MORC1 and MORC6 and thereby link the RdDM pathway and heterochromatin condensation (Liu et al, 2016). However, it is thought that the RdDM pathway is unlikely to be involved in heterochromatin condensation at the whole genome level. Immunohistochemical staining We previously demonstrated that the Su(var)3 9 homologs SUVH2 and SUVH9, which are RdDM components, interact with MORC1 and MORC6 and thereby link the RdDM pathway and heterochromatin condensation (Liu et al, 2016). However, it is thought that the RdDM pathway is unlikely to be involved in heterochromatin condensation at the whole genome level. ChIP‐seq,RNA expression analysis,Immunofluorescence assay,,weston blot MORC1 We previously demonstrated that the Su(var)3 9 homologs SUVH2 and SUVH9, which are RdDM components, interact with MORC1 and MORC6 and thereby link the RdDM pathway and heterochromatin condensation (Liu et al, 2016). However, it is thought that the RdDM pathway is unlikely to be involved in heterochromatin condensation at the whole genome level. 30103804 chr1 150923029 150925029 SETDB1 Results Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. human High+Lowthroughput Loss of SETDB1 decompacts the inactive X chromosome in part through reactivation of an enhancer in the IL1RAPL1 gene 是 rs140261831,rs113985890,rs190632360,rs144991617 Intellectual disability E_01_0765 RT-PCR, Weston blot, immunofluorescence staining, chip SEQ, RNA SEQ, statistical analysis Results Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. Immunohistochemical staining Results Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. RT-PCR,weston blot,免疫荧光染色,ChIP-Seq,RNA-Seq,统计分析 SETDB1 Results Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory. 30102396 chr2 230200488 230202488 SP140 ABSTRACT SP140 locus has been associated with multiple sclerosis (MS) as well as other autoimmune diseases by genome-wide association studies (GWAS). human High+Lowthroughput SP140 regulates the expression of immune-related genes associated with multiple sclerosis and other autoimmune diseases by NF-κB inhibition 是 rs28445040 Multiple sclerosis (MS) B cell E_01_0766 RNA-Seq,weston blot,ddPCR ABSTRACT SP140 locus has been associated with multiple sclerosis (MS) as well as other autoimmune diseases by genome-wide association studies (GWAS). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ABSTRACT SP140 locus has been associated with multiple sclerosis (MS) as well as other autoimmune diseases by genome-wide association studies (GWAS). Immunohistochemical staining ABSTRACT SP140 locus has been associated with multiple sclerosis (MS) as well as other autoimmune diseases by genome-wide association studies (GWAS). RNA-Seq,weston blot,ddPCR SP140 ABSTRACT SP140 locus has been associated with multiple sclerosis (MS) as well as other autoimmune diseases by genome-wide association studies (GWAS). 30100186 chr9 128680671 128682671 SET The activity of the catalytic SET domain (Su(var)3 9, Enhancer-of-zeste and Trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. human High+Lowthroughput Structure and Conformational Dynamics of a COMPASS Histone H3K4 Methyltransferase Complex 否 All, acute lymphoblastic leukaemia Sf9 cell E_01_0767 Weston blot, PCR, statistical analysis The activity of the catalytic SET domain (Su(var)3 9, Enhancer-of-zeste and Trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The activity of the catalytic SET domain (Su(var)3 9, Enhancer-of-zeste and Trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. Immunohistochemical staining The activity of the catalytic SET domain (Su(var)3 9, Enhancer-of-zeste and Trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. weston blot,PCR,统计分析 SET The activity of the catalytic SET domain (Su(var)3 9, Enhancer-of-zeste and Trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. 30097586 chr7 44101429 44103429 AEBP1 Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. human High+Lowthroughput AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-κB pathway and predicts poor outcome of the patients 否 Gastric cancer, nonalcoholic fatty liver disease epithelial cell E_01_0768 QRT PCR, Weston blot, statistical analysis Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. Immunohistochemical staining Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. qRT-PCR,weston blot,统计分析 AEBP1 Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. 30097539 chr3 133743162 133745162 TF Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). At these sites, GR also commonly cobinds with certain pioneer factors, such as AP-1 TFs (Biddie et al. 2011) and CEBPB (Grøntved et al. 2013), which are so designated for their ability to bind sequence motifs in condensed chromatin and to remodel chromatin to increase accessibility (Zaret and Carroll 2011). human High+Lowthroughput Glucocorticoid receptor recruits to enhancers and drives activation by motif-directed binding 否 A549 cell E_01_0769 ChIP-seq,DNase-seq ,PCR,RNA-seq Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). At these sites, GR also commonly cobinds with certain pioneer factors, such as AP-1 TFs (Biddie et al. 2011) and CEBPB (Grøntved et al. 2013), which are so designated for their ability to bind sequence motifs in condensed chromatin and to remodel chromatin to increase accessibility (Zaret and Carroll 2011). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). At these sites, GR also commonly cobinds with certain pioneer factors, such as AP-1 TFs (Biddie et al. 2011) and CEBPB (Grøntved et al. 2013), which are so designated for their ability to bind sequence motifs in condensed chromatin and to remodel chromatin to increase accessibility (Zaret and Carroll 2011). Immunohistochemical staining Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). At these sites, GR also commonly cobinds with certain pioneer factors, such as AP-1 TFs (Biddie et al. 2011) and CEBPB (Grøntved et al. 2013), which are so designated for their ability to bind sequence motifs in condensed chromatin and to remodel chromatin to increase accessibility (Zaret and Carroll 2011). ChIP-seq,DNase-seq ,PCR,RNA-seq TF Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). At these sites, GR also commonly cobinds with certain pioneer factors, such as AP-1 TFs (Biddie et al. 2011) and CEBPB (Grøntved et al. 2013), which are so designated for their ability to bind sequence motifs in condensed chromatin and to remodel chromatin to increase accessibility (Zaret and Carroll 2011). 30092404 chr7 148804297 148806297 EZH2 Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). human High+Lowthroughput A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer 否 Human colorectal cancer (CRC), acute myeloid leukemia E_01_0770 Real time qPCR, Western blot, flow cytometry, statistical analysis Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). Immunohistochemical staining Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). Real-Time qPCR,western Blot,流式细胞术,统计分析 EZH2 Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). 30087711 chr10 31315956 31317956 ZEB1 Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. human High+Lowthroughput Analysis of the expression of cancer-associated fibroblast- and EMT-related proteins in submucosal invasive colorectal cancer 否 colorectal cancer fibroblast E_01_0771 Immunohistochemistry, hierarchical clustering analysis Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. Immunohistochemical staining Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. 免疫组化,层次聚类分析 ZEB1,TWIST1 Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry.;Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. 30087389 chr15 40841317 40843317 SPINT1 The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. human High+Lowthroughput Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2 否 Inflammatory bowel disease, allergic disease, malignancy Caco-2 cell E_01_0772 Chip PCR, RT-PCR, chip SEQ, statistical analysis The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. Immunohistochemical staining The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. ChIP-PCR,RT-PCR,ChIP-seq,统计分析 SPINT1,ST14 CDX2 The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. ;The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1).In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. 30084155 chr16 86507365 86509365 FOXF1 Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, lethal, neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. human High+Lowthroughput LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV 是 Alveolar capillary dysplasia with misalignment of pulmonary veins (acdmpv) germ line cell E_01_0773 PCR Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, lethal, neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, lethal, neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Immunohistochemical staining Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, lethal, neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. PCR FOXF1 Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, lethal, neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. 30082743 chr10 67882384 67884384 SIRT1 We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14. human High+Lowthroughput DBC1 regulates Wnt/β-catenin-mediated expression of MACC1, a key regulator of cancer progression, in colon cancer 否 Colon cancer 1 (MACC1), breast cancer Cancer Stem Cell E_01_0774 QRT PCR, chip SEQ, chip qPCR, immunofluorescence staining, statistical analysis We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14. Immunohistochemical staining We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14. qRT-PCR,ChIP-seq,ChIP-qPCR,免疫荧光染色,统计分析 HDAC3,SUV39H1,MDM2 SIRT1 We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14.;We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14.;We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14. We and others have recently shown that DBC1 plays a key role in multiple oncogenic signaling pathways by acting as a transcriptional coactivator for estrogen receptor, PEA3/ETV4, LEF1-β-catenin, androgen receptor, and androgen receptor variant 7 and by functioning as an inhibitor of epigenetic modifiers such as SIRT1, HDAC3, SUV39H1, MDM2, and CHIP7 14. 30082223 chr11 32384746 32386746 WT1 The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial. human High+Lowthroughput Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia: A?Hokkaido Leukemia Net Study 是 rs16754 Acute myeloid leukemia (AML) K562 cell E_01_0775 Statistical analysis, PCR The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial. Immunohistochemical staining The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial. 统计分析,PCR WT1,NPM1 CEBPA The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial.;The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial. The WT1 protein is a unique transcription factor that can activate or repress target promoters depending on the cellular cofactors it binds to.3 More than 70% of patients with acute myelogenous leukemia (AML) will have overexpression of WT1 at diagnosis. 4-7 Whether the WT1 transcript levels at diagnosis are predictive of the outcomes of AML patients is controversial. 30081852 chr5 5137696 5139696 ADAMTS16 Conclusions We identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors. human Tumor High+Lowthroughput Aberrant DNA methylation of ADAMTS16 in colorectal and other epithelial cancers 是 Oral squamous cell carcinoma (SCC), lung cancer HT29 cell E_01_0776 Western blot, immunohistochemical analysis, statistical analysis Conclusions We identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conclusions We identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors. Immunohistochemical staining Conclusions We identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors. western blot,免疫组化分析,统计分析 ADAMTS16,ADAMTS2 Conclusions We identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors.;Conclusions We identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors. 30078552 chr14 92920852 92922852 CHGA Most islet antigens (Ags), namely insulin (INS) and its precursor preproinsulin (PPI), glutamic acid decarboxylase (GAD65/ GAD2), islet Ag (IA)-2 (PTPRN) (Mallone et al., 2007; Martinuzzi et al., 2008), and zinc transporter 8 (ZnT8/SLC30A8) (Scotto et al., 2012), have been identified based on their targeting by autoantibodies (aAbs). Other Ags such as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Mallone et al., 2007), chromogranin A (CHGA) (Li et al., 2015), and islet amyloid polypeptide (IAPP) (Standifer et al., 2006) have been identified based on studies in the non-obese dia- betic mouse and/or its islet-enriched expression. human High+Lowthroughput Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Na?ve CD8+ T Cells in Type 1 Diabetic and Healthy Donors 否 Type 1 diabetes (T1D) CD8+ T cell E_01_0777 RNA SEQ, immunofluorescence staining, HLA-A2 binding assays Most islet antigens (Ags), namely insulin (INS) and its precursor preproinsulin (PPI), glutamic acid decarboxylase (GAD65/ GAD2), islet Ag (IA)-2 (PTPRN) (Mallone et al., 2007; Martinuzzi et al., 2008), and zinc transporter 8 (ZnT8/SLC30A8) (Scotto et al., 2012), have been identified based on their targeting by autoantibodies (aAbs). Other Ags such as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Mallone et al., 2007), chromogranin A (CHGA) (Li et al., 2015), and islet amyloid polypeptide (IAPP) (Standifer et al., 2006) have been identified based on studies in the non-obese dia- betic mouse and/or its islet-enriched expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Most islet antigens (Ags), namely insulin (INS) and its precursor preproinsulin (PPI), glutamic acid decarboxylase (GAD65/ GAD2), islet Ag (IA)-2 (PTPRN) (Mallone et al., 2007; Martinuzzi et al., 2008), and zinc transporter 8 (ZnT8/SLC30A8) (Scotto et al., 2012), have been identified based on their targeting by autoantibodies (aAbs). Other Ags such as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Mallone et al., 2007), chromogranin A (CHGA) (Li et al., 2015), and islet amyloid polypeptide (IAPP) (Standifer et al., 2006) have been identified based on studies in the non-obese dia- betic mouse and/or its islet-enriched expression. Immunohistochemical staining Most islet antigens (Ags), namely insulin (INS) and its precursor preproinsulin (PPI), glutamic acid decarboxylase (GAD65/ GAD2), islet Ag (IA)-2 (PTPRN) (Mallone et al., 2007; Martinuzzi et al., 2008), and zinc transporter 8 (ZnT8/SLC30A8) (Scotto et al., 2012), have been identified based on their targeting by autoantibodies (aAbs). Other Ags such as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Mallone et al., 2007), chromogranin A (CHGA) (Li et al., 2015), and islet amyloid polypeptide (IAPP) (Standifer et al., 2006) have been identified based on studies in the non-obese dia- betic mouse and/or its islet-enriched expression. RNA-Seq,免疫荧光染色,HLA-A2 Binding Assays PTPRN CHGA Most islet antigens (Ags), namely insulin (INS) and its precursor preproinsulin (PPI), glutamic acid decarboxylase (GAD65/ GAD2), islet Ag (IA)-2 (PTPRN) (Mallone et al., 2007; Martinuzzi et al., 2008), and zinc transporter 8 (ZnT8/SLC30A8) (Scotto et al., 2012), have been identified based on their targeting by autoantibodies (aAbs). Other Ags such as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Mallone et al., 2007), chromogranin A (CHGA) (Li et al., 2015), and islet amyloid polypeptide (IAPP) (Standifer et al., 2006) have been identified based on studies in the non-obese dia- betic mouse and/or its islet-enriched expression. Most islet antigens (Ags), namely insulin (INS) and its precursor preproinsulin (PPI), glutamic acid decarboxylase (GAD65/ GAD2), islet Ag (IA)-2 (PTPRN) (Mallone et al., 2007; Martinuzzi et al., 2008), and zinc transporter 8 (ZnT8/SLC30A8) (Scotto et al., 2012), have been identified based on their targeting by autoantibodies (aAbs). Other Ags such as islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (Mallone et al., 2007), chromogranin A (CHGA) (Li et al., 2015), and islet amyloid polypeptide (IAPP) (Standifer et al., 2006) have been identified based on studies in the non-obese dia- betic mouse and/or its islet-enriched expression. 30076933 chr20 62793633 62795633 MRGBP This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. human High+Lowthroughput MRGBP promotes AR-mediated transactivation of KLK3 and TMPRSS2 via acetylation of histone H2A.Z in prostate cancer cells 否 prostatic cancer LNCaP E_01_0778 QPCR, Western blot, hat assay, statistical analysis This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. Immunohistochemical staining This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. qPCR,western blot,HAT assay,统计分析 MRGBP,KLK3 TMPRSS2 This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. ;This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. 30076409 chr19 15232383 15234383 BRD4 Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. human High+Lowthroughput RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation 否 colorectal cancer SW480 cell E_01_0779 ChIP-qPCR, qRT-PCR,UV-RIP,SPR,ChIP-Seq,EMSA,western blot Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. Immunohistochemical staining Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. ChIP-qPCR, qRT-PCR,UV-RIP,SPR,ChIP-Seq,EMSA,western blot BRDT,BRD7,BRD2 BRD4 Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs.;Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs.;Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. 30072894 chr1 156460893 156462893 MEF2D In conclusion, rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. human High+Lowthroughput Neuroprotection Against MPP(+)-Induced Cytotoxicity Through the Activation of PI3-K/Akt/GSK3β/MEF2D Signaling Pathway by Rhynchophylline, the Major Tetracyclic Oxindole Alkaloid Isolated From Uncaria rhynchophylla 是 Neurodegenerative diseases Parkinson's disease (PD) PC12 cell E_01_0780 Western blot, MTT assay, statistical analysis In conclusion, rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Immunohistochemical staining In conclusion, rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. western blot,MTT法,统计分析 MEF2D In conclusion, rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. 30072891 chr1 207031208 207033208 PFKFB2 In addition, the mRNA expression levels of peroxisome proliferators-activated receptor γ/α (PPARγ/α), CCAAT/enhancer binding proteinα (C/EBPα), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. human High+Lowthroughput Salvianolic Acid B Improves Mitochondrial Function in 3T3-L1 Adipocytes Through a Pathway Involving PPARγ Coactivator-1α (PGC-1α) 否 Obesity, diabetes 3T3‑L1 adipocytes E_01_0781 Real time PCR, immunofluorescence staining In addition, the mRNA expression levels of peroxisome proliferators-activated receptor γ/α (PPARγ/α), CCAAT/enhancer binding proteinα (C/EBPα), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, the mRNA expression levels of peroxisome proliferators-activated receptor γ/α (PPARγ/α), CCAAT/enhancer binding proteinα (C/EBPα), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. Immunohistochemical staining In addition, the mRNA expression levels of peroxisome proliferators-activated receptor γ/α (PPARγ/α), CCAAT/enhancer binding proteinα (C/EBPα), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. real-time PCR,免疫荧光染色 PFKFB2 In addition, the mRNA expression levels of peroxisome proliferators-activated receptor γ/α (PPARγ/α), CCAAT/enhancer binding proteinα (C/EBPα), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. 30071900 chr7 148804109 148806109 EZH2 Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. Post-translational modifications (PTMs) of PCNA facilitate these protein interactions and are essential for the high processivity and accuracy of DNA synthesis. human High+Lowthroughput EZH2 promotes DNA replication by stabilizing interaction of POLδ and PCNA via methylation-mediated PCNA trimerization 否 293T cell E_01_0782 Western blot, flow cytometry analysis, RNA SEQ, 5-ethynyl-2 ′ - deoxyuridine (EDU) staining, immunofluorescence staining, statistical analysis Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. Post-translational modifications (PTMs) of PCNA facilitate these protein interactions and are essential for the high processivity and accuracy of DNA synthesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. Post-translational modifications (PTMs) of PCNA facilitate these protein interactions and are essential for the high processivity and accuracy of DNA synthesis. Immunohistochemical staining Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. Post-translational modifications (PTMs) of PCNA facilitate these protein interactions and are essential for the high processivity and accuracy of DNA synthesis. western blot,流式细胞术分析,RNA-Seq,5-Ethynyl-2′-deoxyuridine (EdU) staining,免疫荧光染色,统计分析 EZH2 Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. Post-translational modifications (PTMs) of PCNA facilitate these protein interactions and are essential for the high processivity and accuracy of DNA synthesis. 30061944 chr7 148804369 148806369 EZH2 Downregulation of EZH2 expression enhanced the anticancer effect of methyl jasmonate on human colorectal cancer cells through suppression of the Wnt/β-catenin pathway. human High+Lowthroughput EZH2 inhibition promotes methyl jasmonate-induced apoptosis of human colorectal cancer through the Wnt/β-catenin pathway 否 Colorectal cancer, leukemia T24 cell E_01_0783 Western blot, statistical analysis, flow cytometry Downregulation of EZH2 expression enhanced the anticancer effect of methyl jasmonate on human colorectal cancer cells through suppression of the Wnt/β-catenin pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Downregulation of EZH2 expression enhanced the anticancer effect of methyl jasmonate on human colorectal cancer cells through suppression of the Wnt/β-catenin pathway. Immunohistochemical staining Downregulation of EZH2 expression enhanced the anticancer effect of methyl jasmonate on human colorectal cancer cells through suppression of the Wnt/β-catenin pathway. western blot,统计分析,流式细胞术 EZH2 Downregulation of EZH2 expression enhanced the anticancer effect of methyl jasmonate on human colorectal cancer cells through suppression of the Wnt/β-catenin pathway. 30059522 chr8 91154296 91156296 CPP As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP. human Epithelial High+Lowthroughput mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446 否 Cystic fibrosis epithelial cell E_01_0784 Western blot, immunofluorescence staining As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP. Immunohistochemical staining As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP. western blot,免疫荧光染色 CPP As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP. 30054476 chr10 128093460 128095460 MKI67 MGMT expression can be silenced by the methylation of a promoter/enhancer (P/E) region, which contains a promoter and a 59 bp cis-acting enhancer element that spans the first exon intron boundary of MGMT gene4. human High+Lowthroughput A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma 否 Glioblastoma E_01_0785 Western blot, real-time PCR, RNA SEQ, MS-PCR, chip SEQ, statistical analysis MGMT expression can be silenced by the methylation of a promoter/enhancer (P/E) region, which contains a promoter and a 59 bp cis-acting enhancer element that spans the first exon intron boundary of MGMT gene4. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MGMT expression can be silenced by the methylation of a promoter/enhancer (P/E) region, which contains a promoter and a 59 bp cis-acting enhancer element that spans the first exon intron boundary of MGMT gene4. Immunohistochemical staining MGMT expression can be silenced by the methylation of a promoter/enhancer (P/E) region, which contains a promoter and a 59 bp cis-acting enhancer element that spans the first exon intron boundary of MGMT gene4. Western blot,real-time PCR,RNA-seq,MS-PCR,ChIP-seq,统计分析 MKI67,MGMT MGMT expression can be silenced by the methylation of a promoter/enhancer (P/E) region, which contains a promoter and a 59 bp cis-acting enhancer element that spans the first exon intron boundary of MGMT gene4. ;MGMT expression can be silenced by the methylation of a promoter/enhancer (P/E) region, which contains a promoter and a 59 bp cis-acting enhancer element that spans the first exon intron boundary of MGMT gene4. 30053869 chr3 41192055 41194055 CTNNB1 Results In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. human High+Lowthroughput Difference in transducin-like enhancer of split 1 protein expression between basal cell adenomas and basal cell adenocarcinomas - an immunohistochemical study Basal cell adenoma (BCA), basal cell adenocarcinoma (BCAC) acinar cell E_01_0786 Immunohistochemistry and analysis,PCR Results In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. Immunohistochemical staining Results In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. Immunohistochemistry and analysis,PCR CTNNB1,TLE1 Results In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. ;Results In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. 30048163 chr7 148804302 148806302 EZH2 Results: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. human High+Lowthroughput Downregulation of Long Noncoding RNA HOTAIR and EZH2 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Breast Cancer Cells 否 mammary cancer MCF7 cell E_01_0787 MTT assay, RT qPCR, flow cytometry, statistical analysis Results: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. Immunohistochemical staining Results: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. MTT assay, RT-qPCR,流式细胞术,统计分析 EZH2,HOTAIR Results: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected.;Results: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. 30042166 chr18 58668913 58670913 MALT1 Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues. human Glioma High+Lowthroughput LncRNA SNHG3 enhances the malignant progress of glioma through silencing KLF2 and p21 否 OSCC, colorectal, hepatocellular carcinoma SHG-44 cell E_01_0788 QRT PCR, Western blot, chromatin immunoprecipitation, RNA immunoprecipitation (RIP), statistical analysis, flow cytometry Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues. Immunohistochemical staining Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues. qRT-PCR,Western blot,Chromatin immunoprecipitation,RNA immunoprecipitation (RIP),统计分析,流式细胞术 MALT1,CRNDE KLF2 Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues.;Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues. Besides, it was also found out that KLF2 and p21 were down-regulated in glioma tissues. 30042132 chr3 181708868 181710868 SOX2 Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Ewing sarcoma, the second most common pediatric bone cancer, is characterized by specific chromosomal translocations that generate fusions between the EWSR1 gene and members of the ETS family of transcription factors, most commonly FLI1 (Delattre et al. 1992). human High+Lowthroughput Epigenome editing of microsatellite repeats defines tumor-specific enhancer functions and dependencies 否 Ewing sarcoma SK-N-MC cell E_01_0789 RT qPCR, Western blot, chip SEQ, chip qPCR, NRO RT qPCR, NRO SEQ, statistical analysis Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Ewing sarcoma, the second most common pediatric bone cancer, is characterized by specific chromosomal translocations that generate fusions between the EWSR1 gene and members of the ETS family of transcription factors, most commonly FLI1 (Delattre et al. 1992). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Ewing sarcoma, the second most common pediatric bone cancer, is characterized by specific chromosomal translocations that generate fusions between the EWSR1 gene and members of the ETS family of transcription factors, most commonly FLI1 (Delattre et al. 1992). Immunohistochemical staining Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Ewing sarcoma, the second most common pediatric bone cancer, is characterized by specific chromosomal translocations that generate fusions between the EWSR1 gene and members of the ETS family of transcription factors, most commonly FLI1 (Delattre et al. 1992). RT-qPCR,Western blot,ChIP-seq,ChIP-qPCR,NRO-RT-qPCR,NRO-seq,统计分析 SOX2,EWSR1 Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Ewing sarcoma, the second most common pediatric bone cancer, is characterized by specific chromosomal translocations that generate fusions between the EWSR1 gene and members of the ETS family of transcription factors, most commonly FLI1 (Delattre et al. 1992).;Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Ewing sarcoma, the second most common pediatric bone cancer, is characterized by specific chromosomal translocations that generate fusions between the EWSR1 gene and members of the ETS family of transcription factors, most commonly FLI1 (Delattre et al. 1992). 30038060 chr4 25645137 25647137 SLC34A2 Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. human High+Lowthroughput The SLC34A2-ROS-HIF-1-induced up-regulation of EZH2 expression promotes proliferation and chemo-resistance to apoptosis in colorectal cancer 否 Colorectal, ovarian, breast, gastric, lung HT29 cell E_01_0790 Quantitative real-time RT-PCR, Western blot, MTT assay, TUNEL assay, FACS analysis, statistical analysis, gene knockdown Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. Immunohistochemical staining Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. Quantitative real-time RT-PCR,Western blot,MTT assay,TUNEL assay,FACS分析,统计分析,基因敲降 SLC34A2 EZH2 Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. We demonstrated that SLC34A2 induced EZH2 expression and activated its promoter activity. 30037979 chr17 10626067 10628067 MYH3 MUNC is required for optimal myogenic differentiation, induces specific myogenic transcripts in trans (MYOD, MYOGENIN, and MYH3), and has a functional human homolog. human High+Lowthroughput MUNC, an Enhancer RNA Upstream from the MYOD Gene, Induces a Subgroup of Myogenic Transcripts in trans Independently of MyoD 否 C2C12 cell E_01_0791 qRT-PCR,Western blot,Southern blot,Immunofluorescence assay,RNA-Seq MUNC is required for optimal myogenic differentiation, induces specific myogenic transcripts in trans (MYOD, MYOGENIN, and MYH3), and has a functional human homolog. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MUNC is required for optimal myogenic differentiation, induces specific myogenic transcripts in trans (MYOD, MYOGENIN, and MYH3), and has a functional human homolog. Immunohistochemical staining MUNC is required for optimal myogenic differentiation, induces specific myogenic transcripts in trans (MYOD, MYOGENIN, and MYH3), and has a functional human homolog. qRT-PCR,Western blot,Southern blot,Immunofluorescence assay,RNA-Seq MYH3 MUNC is required for optimal myogenic differentiation, induces specific myogenic transcripts in trans (MYOD, MYOGENIN, and MYH3), and has a functional human homolog. 30036660 chr1 161763256 161765256 ATF6 This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. human High+Lowthroughput Apelin-13 Alleviates Early Brain Injury after Subarachnoid Hemorrhage via Suppression of Endoplasmic Reticulum Stress-mediated Apoptosis and Blood-Brain Barrier Disruption: Possible Involvement of ATF6/CHOP Pathway 否 Subarachnoid hemorrhage neuronal cell E_01_0792 RT-PCR, immunofluorescence staining, Western blot This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. Immunohistochemical staining This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. RT-PCR, 免疫荧光染色,western blot ATF6 This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. 30033370 chr8 127732613 127734613 MYC Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer. human High+Lowthroughput Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer 否 prostatic cancer neoplastic cell E_01_0793 RNA sequencing, statistical analysis Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer. Immunohistochemical staining Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer. RNA Sequencing,统计分析 MYC,BRCA2 Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.;Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer. 30033362 chr19 41447287 41449287 PCAT19 We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). human High+Lowthroughput Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19 是 rs11672691,rs887391,rs35148638,rs78943174 prostatic cancer LNCaP E_01_0794 RNA pull-down (chirp) assay, RT qPCR, Western blot, RNA SEQ, eQTL analysis, crispri assay, statistical analysis We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). Immunohistochemical staining We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). RNA pull-down (ChIRP) assay,RT-qPCR,Western blot,RNA-seq,eQTL分析,CRISPRi assay,统计分析 PCAT19 We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). 30033361 chr19 41446587 41448587 PCAT19 We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. human High+Lowthroughput Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus 是 rs11672691 Aggressive prostate cancer (PCA) RWPE1 cell E_01_0795 STARR-seq,eQTL analysis,Quantitative RT-PCR,Chromatin immunoprecipitation (ChIP),Western Blot,RNA-Seq We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Immunohistochemical staining We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. STARR-seq,eQTL analysis,Quantitative RT-PCR,Chromatin immunoprecipitation (ChIP),Western Blot,RNA-Seq PCAT19,CEACAM21 HOXA2 We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa.;We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated mRNA levels of two biologically plausible candidate genes PCAT19 and CEACAM21, implicating in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. 30026867 chr16 4253924 4255924 TFAP4 It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1). human High+Lowthroughput Transcription factor AP-4 promotes tumorigenic capability and activates the Wnt/β-catenin pathway in hepatocellular carcinoma 否 Hepatocellular carcinoma HCC cell E_01_0796 Western blot, immunohistochemistry, chip qPCR, flow cytometry, statistical analysis It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1). Immunohistochemical staining It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1). western blot,Immunohistochemistry,ChIP-qPCR,流式细胞术,统计分析 TFAP4,LEF1 It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1). ;It has been reported that the transcription factor activating enhancer-binding protein 4 (TFAP4) is upregulated and associated with an aggressive phenotype in several cancers. Mechanistically, we demonstrated that TFAP4 played an important role in activating Wnt/β-catenin signaling by directly binding to the promoters of DVL1 (dishevelled segment polarity protein 1) and LEF1 (lymphoid enhancer binding factor 1). 30026326 chr12 50760530 50762530 ATF1 We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. human High+Lowthroughput A Rare Missense Variant in TCF7L2 Associates with Colorectal Cancer Risk by Interacting with a GWAS-Identified Regulatory Variant in the MYC Enhancer 是 rs111169571,rs138649767,rs6983267 Colorectal cancer (CRC) E_01_0797 ATF1 ChIP-seq,PCR We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. Immunohistochemical staining We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. ATF1 ChIP-seq,PCR NRAS ATF1,TCF7L2,MYC,BRAF We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. ;We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. ;We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. ;We found a significant interaction between the TCF7L2 missense48 variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the49 MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that50 TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with51 rs6983267-G allele and enhance CRC cell proliferation. Further ChIP-seq and gene co-expression analyses showed that54 oncogenes NRAS and BRAF were activated by ATF1 in CRC. 30022673 chr4 109910279 109912279 EGF The immortalised cells were routinely propagated in Opti-MEM, supplemented with 4% v/v fetal bovine serum (FBS), 2mM L-glutamine, 2mM GlutaMAX, 10mM 4-(2-hydroxyethyl)-1-piperazineethanesul- phonic acid (HEPES), 20ng/ml Epidermal Growth Factor (EGF), 10 g/ml insulin, and 150nM hydrocor- tisone, and were incubated at 32 C, 6% v/v CO 2 in a humidified atmosphere. human High+Lowthroughput Characterisation of a canine epithelial cell line for modelling the intestinal barrier 否 Colorectal Adenocarcinoma Caco-2 cell E_01_0798 NF -  B assay, flow cytometry, statistical analysis, immunofluorescence staining The immortalised cells were routinely propagated in Opti-MEM, supplemented with 4% v/v fetal bovine serum (FBS), 2mM L-glutamine, 2mM GlutaMAX, 10mM 4-(2-hydroxyethyl)-1-piperazineethanesul- phonic acid (HEPES), 20ng/ml Epidermal Growth Factor (EGF), 10 g/ml insulin, and 150nM hydrocor- tisone, and were incubated at 32 C, 6% v/v CO 2 in a humidified atmosphere. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The immortalised cells were routinely propagated in Opti-MEM, supplemented with 4% v/v fetal bovine serum (FBS), 2mM L-glutamine, 2mM GlutaMAX, 10mM 4-(2-hydroxyethyl)-1-piperazineethanesul- phonic acid (HEPES), 20ng/ml Epidermal Growth Factor (EGF), 10 g/ml insulin, and 150nM hydrocor- tisone, and were incubated at 32 C, 6% v/v CO 2 in a humidified atmosphere. Immunohistochemical staining The immortalised cells were routinely propagated in Opti-MEM, supplemented with 4% v/v fetal bovine serum (FBS), 2mM L-glutamine, 2mM GlutaMAX, 10mM 4-(2-hydroxyethyl)-1-piperazineethanesul- phonic acid (HEPES), 20ng/ml Epidermal Growth Factor (EGF), 10 g/ml insulin, and 150nM hydrocor- tisone, and were incubated at 32 C, 6% v/v CO 2 in a humidified atmosphere. NF-B assay,流式细胞术,统计分析,免疫荧光染色 EGF The immortalised cells were routinely propagated in Opti-MEM, supplemented with 4% v/v fetal bovine serum (FBS), 2mM L-glutamine, 2mM GlutaMAX, 10mM 4-(2-hydroxyethyl)-1-piperazineethanesul- phonic acid (HEPES), 20ng/ml Epidermal Growth Factor (EGF), 10 g/ml insulin, and 150nM hydrocor- tisone, and were incubated at 32 C, 6% v/v CO 2 in a humidified atmosphere. 30021349 chr7 27195996 27197996 HOTTIP Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. human High+Lowthroughput Long non-coding RNA HOTTIP is upregulated in renal cell carcinoma and regulates cell growth and apoptosis by epigenetically silencing of LATS2 否 Renal cell carcinoma (RCC) OS-RC2 cell E_01_0799 RT qPCR, chromatin immunoprecipitation (chip) analysis, Western blot, statistical analysis, immunoblotting analysis Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. Immunohistochemical staining Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. RT-qPCR,Chromatin immunoprecipitation (ChIP) analysi,western blot,统计分析,Immunoblotting analysis HOTTIP,LATS2 EZH2 Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression.;Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. 30016766 chr1 204187679 204189679 KISS1 We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. human High+Lowthroughput LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway 否 Renal cell carcinoma (RCC) renal cancer cell E_01_0800 Real time PCR, flow cytometry, Western blot We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Immunohistochemical staining We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. real-time PCR,流式细胞术,western blot KISS1 EZH2 We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. 30016502 chr21 34784861 34786861 RUNX1 The AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1). Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that CEBPB may be a co-activator. human High+Lowthroughput A novel transcriptional network for the androgen receptor in human epididymis epithelial cells 否 prostatic cancer E_01_0801 Reverse transcription quantitative PCR, RNA SEQ, chip SEQ, chip qPCR, statistical analysis The AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1). Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that CEBPB may be a co-activator. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1). Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that CEBPB may be a co-activator. Immunohistochemical staining The AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1). Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that CEBPB may be a co-activator. Reverse transcription quantitative PCR,RNA-seq,ChIP-seq,ChIP-qPCR,统计分析 RUNX1,FOXA1 The AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1). Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that CEBPB may be a co-activator. ;The AR transcriptional network is tissue-specific and may be mediated in part by distinct AR co-factors including CAAT-enhancer binding protein beta (CEBPB) and runt-related transcription factor 1 (RUNX1). Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that CEBPB may be a co-activator. 30015909 chr2 238235826 238237826 HES6 HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. human High+Lowthroughput Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/β-catenin signaling pathway in colorectal cancer 否 Prostate, breast, colorectal (CRC), lung E_01_0802 RT-qPCR,Western blot,Immunohistochemistry (IHC),Dual-Luciferase assay HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. Immunohistochemical staining HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. RT-qPCR,Western blot,Immunohistochemistry (IHC),Dual-Luciferase assay HES6 HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. 30006149 chr1 116511683 116513683 CD58 Abstract CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co- stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. human High+Lowthroughput Protective C allele of the single-nucleotide polymorphism rs1335532 is associated with strong binding of Ascl2 transcription factor and elevated CD58 expression in B-cells 是 rs2300747,rs1335532 Multiple sclerosis (MS) leukocyte E_01_0803 Pull down assay, real time PCR, Western blot, statistical analysis, gene knockdown Abstract CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co- stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Abstract CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co- stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. Immunohistochemical staining Abstract CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co- stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. Pull-Down Assay,Real-Time PCR,Western Blot,统计分析,基因敲降 CD58 ASCL2 Abstract CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co- stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. Abstract CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co- stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. 29991769 chr4 108044640 108046640 LEF1 Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. human High+Lowthroughput Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a 否 Osteoporosis fat cell E_01_0804 RT qPCR, immunoprecipitation, immunoblotting and co immunoprecipitation, statistical analysis Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. Immunohistochemical staining Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. RT-qPCR,Immunoprecipitation, immunoblotting and co-immunoprecipitation,统计分析 Runx2 LEF1 Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. 29988121 chr16 67559717 67561717 CTCF Similarly, in population-based assays, individual CTCF sites can be seen con- tacting multiple other CTCF sites. human High+Lowthroughput Enhancer hubs and loop collisions identified from single-allele topologies 否 cancer hepatocyte E_01_0805 MC-4C viewpoint specific PCR, Hi-C sequencing Similarly, in population-based assays, individual CTCF sites can be seen con- tacting multiple other CTCF sites. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Similarly, in population-based assays, individual CTCF sites can be seen con- tacting multiple other CTCF sites. Immunohistochemical staining Similarly, in population-based assays, individual CTCF sites can be seen con- tacting multiple other CTCF sites. MC-4C viewpoint-specific PCR,Hi-C测序 CTCF Similarly, in population-based assays, individual CTCF sites can be seen con- tacting multiple other CTCF sites. 29986647 chr4 88004722 88006722 PKD2 Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. human High+Lowthroughput Novel long-range regulatory mechanisms controlling PKD2 gene expression 否 Polycystic kidney disease (ADPKD), lung cancer epithelial cell E_01_0806 PCR,Hi-C Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. Immunohistochemical staining Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. PCR,Hi-C PKD2 CTCF Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). Conclusions Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. 29983891 chr11 1072345 1074345 MUC2 Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. human High+Lowthroughput Cancer-predicting transcriptomic and epigenetic signatures revealed for ulcerative colitis in patient-derived epithelial organoids 否 Ulcerative colitis (UC) goblet cell E_01_0807 Immunohistochemistry, RNA SEQ, real time PCR, chip SEQ, statistical analysis Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. Immunohistochemical staining Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. 免疫组织化学,RNA-Seq,Real-time PCR,ChIP-seq,统计分析 MUC2,LYZ Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. ;Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. 29977016 chr7 50301609 50303609 IKZF1 Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. human High+Lowthroughput Genetic predisposition to B-cell acute lymphoblastic leukemia at 14q11.2 is mediated by a CEBPE promoter polymorphism 是 rs2239630 Acute lymphoblastic leukemia (all) B cell E_01_0808 Chip SEQ, QRT PCR, RNA SEQ, flow cytometry Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. Immunohistochemical staining Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. ChIP-seq,qRT-PCR,RNA-Seq,流式细胞术 IKZF1,PAX5,CEBPE Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression.;Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression.;Correspondingly, crucial B-cell development transcription factors IKZF1, PAX5, and EBF1 are also the targets of frequent somatic mutation [11, 12], highlighting that GWAS signals and somatic mutations may impact upon the same genes. The rs2239630-A risk allele is associated with increased promotor activity and CEBPE expression. 29970899 chr7 148804543 148806543 EZH2 In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. human High+Lowthroughput Epigenetic silencing of tumor suppressor gene CDKN1A by oncogenic long non-coding RNA SNHG1 in cholangiocarcinoma 否 Cholangiocarcinoma (CCA) CCA cell E_01_0809 QRT PCR, Western blot, flow cytometry, rip assays, chip assays, immunofluorescence, statistical analysis, gene knockdown, RNA seq In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. Immunohistochemical staining In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. qRT-PCR,Western blot,流式细胞术,RIP assays,ChIP assays,Immunofluorescence,统计分析,基因敲降,RNA-Seq SNHG1 EZH2 In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. 29964053 chrX 67541163 67543163 AR Specifically, eRNA MARC1 (eMARC1), transcribed from androgen receptor (AR) activated enhancer that was responsible for activation of nearby coding transcription units [20, 21], was identified as an androgen associated AR-activated eRNA [22]. human BCA High+Lowthroughput High expression of enhancer RNA MARC1 or its activation by DHT is associated with the malignant behavior in bladder cancer 否 Bladder cancer (BCA) Bca cell E_01_0810 Real time quantitative PCR, flow cytometry, statistical analysis Specifically, eRNA MARC1 (eMARC1), transcribed from androgen receptor (AR) activated enhancer that was responsible for activation of nearby coding transcription units [20, 21], was identified as an androgen associated AR-activated eRNA [22]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Specifically, eRNA MARC1 (eMARC1), transcribed from androgen receptor (AR) activated enhancer that was responsible for activation of nearby coding transcription units [20, 21], was identified as an androgen associated AR-activated eRNA [22]. Immunohistochemical staining Specifically, eRNA MARC1 (eMARC1), transcribed from androgen receptor (AR) activated enhancer that was responsible for activation of nearby coding transcription units [20, 21], was identified as an androgen associated AR-activated eRNA [22]. Real-time quantitative PCR,流式细胞术,统计分析 AR Specifically, eRNA MARC1 (eMARC1), transcribed from androgen receptor (AR) activated enhancer that was responsible for activation of nearby coding transcription units [20, 21], was identified as an androgen associated AR-activated eRNA [22]. 29963192 chr1 156460745 156462745 MEF2D In the present study, it was found that MEF2D and miR-30a were inversely correlated in lung cancer samples. human High+Lowthroughput Absent expression of miR-30a promotes the growth of lung cancer cells by targeting MEF2D 否 lung cancer A549 cell E_01_0811 RT qPCR, Western blot, statistical analysis, flow cytometry In the present study, it was found that MEF2D and miR-30a were inversely correlated in lung cancer samples. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, it was found that MEF2D and miR-30a were inversely correlated in lung cancer samples. Immunohistochemical staining In the present study, it was found that MEF2D and miR-30a were inversely correlated in lung cancer samples. RT-qPCR,Western blot,统计分析,流式细胞术 MEF2D In the present study, it was found that MEF2D and miR-30a were inversely correlated in lung cancer samples. 29956121 chr3 189628865 189630865 TP63 Abstract Purpose Genome-wide association studies (GWAS) have led to the identification of a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role in the transcriptional regulation of these genes. human High+Lowthroughput Identification of an enhancer region within the TP63/LEPREL1 locus containing genetic variants associated with bladder cancer risk 是 rs710521,rs6983267 Bladder cancer (BCA) bladder cancer cell E_01_0812 Faire, RT qPCR, statistical analysis Abstract Purpose Genome-wide association studies (GWAS) have led to the identification of a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role in the transcriptional regulation of these genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Abstract Purpose Genome-wide association studies (GWAS) have led to the identification of a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role in the transcriptional regulation of these genes. Immunohistochemical staining Abstract Purpose Genome-wide association studies (GWAS) have led to the identification of a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role in the transcriptional regulation of these genes. FAIRE,RT-qPCR,统计分析 TP63 Abstract Purpose Genome-wide association studies (GWAS) have led to the identification of a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role in the transcriptional regulation of these genes. 29949917 chr11 118744735 118746735 DDX6 Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). human High+Lowthroughput The RNA Helicase DDX6 Associates with RIG-I to Augment Induction of Antiviral Signaling 否 influenza 293T cell E_01_0813 Immunoprecipitation, quantitative RT-PCR, ELISA, statistical analysis Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). Immunohistochemical staining Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). Immunoprecipitation,Quantitative RT-PCR,ELISA,统计分析 DDX6 Among them was the RIG-I related RNA helicase DEAD box helicase 6 (DDX6), a known component of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules like P-bodies and stress granules (SGs). 35121888 chr2 15938207 15940207 MYCN Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. human High+Lowthroughput Super enhancers define regulatory subtypes and cell identity in neuroblastoma 不相关 Neuroblastoma endothelial cell,Neuroblastoma E_01_0814 Identification of SEs and CRCs,ACE-seq,HiChIP experiments,ATAC-seq Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. Immunohistochemical staining Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. Identification of SEs and CRCs,ACE-seq,HiChIP experiments,ATAC-seq MYCN Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. 34109280 chr12 24807287 24809287 BCAT1 In NRASG12D-mutant myeloproliferative neoplasms, EZH2 deficiency is associated with elevated expression of BCAT1. human High+Lowthroughput The Bidirectional Relationship Between Cancer Epigenetics and Metabolism 不相关 cancer cancer cell E_01_0815 Histone methylation, In NRASG12D-mutant myeloproliferative neoplasms, EZH2 deficiency is associated with elevated expression of BCAT1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In NRASG12D-mutant myeloproliferative neoplasms, EZH2 deficiency is associated with elevated expression of BCAT1. Immunohistochemical staining In NRASG12D-mutant myeloproliferative neoplasms, EZH2 deficiency is associated with elevated expression of BCAT1. 组蛋白甲基化, BCAT1 In NRASG12D-mutant myeloproliferative neoplasms, EZH2 deficiency is associated with elevated expression of BCAT1. 33994736 chr1 245746404 245748404 SMYD3 The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. human High+Lowthroughput Analysis of SET and MYND Domain-Containing Protein 3 (SMYD3) Expression in Gallbladder Cancer: a Pilot Study 不相关 cancer tumor cell E_01_0816 Immunohistochemical (IHC) analysis, The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. Immunohistochemical staining The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. 免疫组化 （IHC） 分析， SMYD3 The role of SMYD3 in gallbladder cancer (GBC) still needs to be studied. In the present study, we examined the SMYD3 gene expression at mRNA and protein level to look its impact on risk for developing gallbladder carcinogenesis. 33777677 chr19 4171328 4173328 SIRT6 We designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264. human connective High+Lowthroughput A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis 不相关 Ischemic stroke macrophage E_01_0817 SIRT6 protein purification and fluorescence cleavage assay (FDL), enzyme linked immunosorbent assay, Western blot analysis, chromatin immunoprecipitation (chip) assay, immunoprecipitation and immunoblotting We designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264. Immunohistochemical staining We designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264. SIRT6蛋白纯化和荧光裂解测定（FDL）,酶联免疫吸附测定,蛋白质印迹分析,染色质免疫沉淀（ChIP）测定,免疫沉淀和免疫印迹 SIRT6 We designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264. 33763107 chr7 148804661 148806661 EZH2 Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. human High+Lowthroughput Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis 不相关 oophoroma ovarian cancer cell E_01_0818 Real time PCR, Western blotting, chromatin immunoprecipitation (chip) Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. Immunohistochemical staining Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. 实时荧光定量 PCR ，蛋白质印记，染色质免疫沉淀 （ChIP） EZH2 Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. 33753020 chr11 116786522 116788522 APOA5 The strongest associations in GWASs were two single-nucleotide polymorphisms (SNPs), rs964184 and rs651821,within different but adjacent genes,ZPR1 zinc finger (ZPR1) and APOA5. human connective High+Lowthroughput Fine genetic mapping of the chromosome 11q23.3 region in a Han Chinese population: insights into the apolipoprotein genes underlying the blood lipid-lipoprotein variances 相关 rs964184,rs651821 Cardiovascular disease hepatocyte E_01_0819 Sequencing and genotyping， Lookups of eQTL data and regulatory mechanisms. Joint fine-mapping analyses integrating functional data The strongest associations in GWASs were two single-nucleotide polymorphisms (SNPs), rs964184 and rs651821,within different but adjacent genes,ZPR1 zinc finger (ZPR1) and APOA5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The strongest associations in GWASs were two single-nucleotide polymorphisms (SNPs), rs964184 and rs651821,within different but adjacent genes,ZPR1 zinc finger (ZPR1) and APOA5. Immunohistochemical staining The strongest associations in GWASs were two single-nucleotide polymorphisms (SNPs), rs964184 and rs651821,within different but adjacent genes,ZPR1 zinc finger (ZPR1) and APOA5. Sequencing and genotyping， Lookups of eQTL data and regulatory mechanisms. Joint fine-mapping analyses integrating functional data APOA5 The strongest associations in GWASs were two single-nucleotide polymorphisms (SNPs), rs964184 and rs651821,within different but adjacent genes,ZPR1 zinc finger (ZPR1) and APOA5. 33718109 chr7 148804493 148806493 EZH2 Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. human High+Lowthroughput EZH2-miRNA Positive Feedback Promotes Tumor Growth in Ovarian Cancer 不相关 oophoroma cancer cell E_01_0820 Real time PCR, Western blot analysis, chromatin immunoprecipitation assay, immunohistochemistry Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. Immunohistochemical staining Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. 实时荧光定量 PCR，蛋白质印迹分析，染色质免疫沉淀测定，免疫组化 EZH2 Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. 33650655 chr15 41318452 41320452 NUSAP1 As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. human Musculature High+Lowthroughput Nucleolar and spindle?associated protein 1 promotes non?small cell lung cancer progression and serves as an effector of myocyte enhancer factor 2D 不相关 lung cancer myocyte E_01_0821 Luciferase assay, reverse transcription quantitative PCR (RT qPCR) analysis, As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. Immunohistochemical staining As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. 荧光素酶测定，逆转录定量 PCR （RT-qPCR） 分析， NUSAP1 As a potential oncogene, nucleolar and spindle-associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. 33520978 chr19 47400663 47402663 MEIS3 Dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. human High+Lowthroughput Tumor-Suppressive Role of microRNA-202-3p in Hepatocellular Carcinoma Through the KDM3A/HOXA1/MEIS3 Pathway 不相关 Hepatocellular carcinoma hepatocyte E_01_0822 Western blot analysis, RNA extraction and quantitative real-time PCR (QRT PCR) analysis Dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. Immunohistochemical staining Dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. 蛋白质印迹分析，RNA 提取和定量实时荧光定量 PCR （qRT-PCR） 分析 MEIS3 Dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. 33068224 chr1 156461073 156463073 MEF2D Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). human High+Lowthroughput CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis. 不相关 Gliomas Glioma cell E_01_0823 Quantitative Real‑Time Polymerase Chain Reaction (qRT‑PCR)，Cell Transfection Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). Immunohistochemical staining Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). Quantitative Real‑Time Polymerase Chain Reaction (qRT‑PCR)，Cell Transfection MEF2D Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). 33461200 chr7 148804344 148806344 EZH2 As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. human High+Lowthroughput Targeting EZH2 Ameliorates the LPS-Inhibited PDLSC Osteogenesis via Wnt/β-Catenin Pathway 不相关 inflammation Periodontal stem cell E_01_0824 Flow cytometric analysis, cell transfection, alkaline phosphatase assay, enzyme linked immunosorbent assay, real time RT-PCR As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. Immunohistochemical staining As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. 流式细胞术分析,细胞转染，碱性磷酸酶测定，Enzyme-Linked Immunosorbent Assay，Real-Time RT-PCR EZH2 As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. 33455270 chr6 45324897 45326897 RUNX2 Runt-related transcription factor 2 (RUNX2) is a master regulator of the osteogenic commitment of hMSCs. human High+Lowthroughput Intracellular Delivery of Recombinant RUNX2 Facilitated by Cell-Penetrating Protein for the Osteogenic Differentiation of hMSCs 不相关 Skull defects mesenchymal stem cell E_01_0825 Protein expression and purification，SDS-PAGE and western blot analysis Runt-related transcription factor 2 (RUNX2) is a master regulator of the osteogenic commitment of hMSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Runt-related transcription factor 2 (RUNX2) is a master regulator of the osteogenic commitment of hMSCs. Immunohistochemical staining Runt-related transcription factor 2 (RUNX2) is a master regulator of the osteogenic commitment of hMSCs. Protein expression and purification，SDS-PAGE and western blot analysis RUNX2 Runt-related transcription factor 2 (RUNX2) is a master regulator of the osteogenic commitment of hMSCs. 33370552 chr7 148804266 148806266 EZH2 Our studies are aimed to investigate the expression of enhancer of zeste homolog 2 (EZH2) in IHD and regulation of cardiac NaV1.5 expression by EZH2. human Musculature High+Lowthroughput Elevated EZH2 in ischemic heart disease epigenetically mediates suppression of Na(V)1.5 expression 相关 rs6801957 ischemic heart disease cardiac muscle cell (sensu Arthopoda) E_01_0826 Chip qPCR, immunofluorescence staining Our studies are aimed to investigate the expression of enhancer of zeste homolog 2 (EZH2) in IHD and regulation of cardiac NaV1.5 expression by EZH2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our studies are aimed to investigate the expression of enhancer of zeste homolog 2 (EZH2) in IHD and regulation of cardiac NaV1.5 expression by EZH2. Immunohistochemical staining Our studies are aimed to investigate the expression of enhancer of zeste homolog 2 (EZH2) in IHD and regulation of cardiac NaV1.5 expression by EZH2. ChIP-qPCR，免疫荧光染色 EZH2 Our studies are aimed to investigate the expression of enhancer of zeste homolog 2 (EZH2) in IHD and regulation of cardiac NaV1.5 expression by EZH2. 33355129 chr22 43148897 43150897 TSPO The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. human High+Lowthroughput Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response 不相关 cancer cell E_01_0827 Immunohistochemistry / immunocytochemistry, Western blotting, confocal imaging, fluorescence imaging The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. Immunohistochemical staining The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. 免疫组化/免疫细胞化学，蛋白质印迹，共聚焦成像，荧光成像 TSPO The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. 33349155 chr17 39725778 39727778 MIEN1 miR-124-5p targeted MIEN1 and negatively modulated the MIEN1 expression in SGC-803 and SGC7901 cells. Silencing MIEN1 negatively regulated the metastasis and proliferation ability of SGC7901 cells. human High+Lowthroughput MiR-124-5p Inhibits the Progression of Gastric Cancer by Targeting MIEN1 不相关 gastric cancer GC cell，SGC803 cell E_01_0828 Dual luciferase reporter assay, QRT PCR miR-124-5p targeted MIEN1 and negatively modulated the MIEN1 expression in SGC-803 and SGC7901 cells. Silencing MIEN1 negatively regulated the metastasis and proliferation ability of SGC7901 cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq miR-124-5p targeted MIEN1 and negatively modulated the MIEN1 expression in SGC-803 and SGC7901 cells. Silencing MIEN1 negatively regulated the metastasis and proliferation ability of SGC7901 cells. Immunohistochemical staining miR-124-5p targeted MIEN1 and negatively modulated the MIEN1 expression in SGC-803 and SGC7901 cells. Silencing MIEN1 negatively regulated the metastasis and proliferation ability of SGC7901 cells. 双荧光素酶报告检测，qRT-PCR MIEN1 miR-124-5p targeted MIEN1 and negatively modulated the MIEN1 expression in SGC-803 and SGC7901 cells. Silencing MIEN1 negatively regulated the metastasis and proliferation ability of SGC7901 cells. 33100045 chr3 192136683 192138683 FGF12 In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. human Musculature High+Lowthroughput FGF12 (Fibroblast Growth Factor 12) Inhibits Vascular Smooth Muscle Cell Remodeling in Pulmonary Arterial Hypertension 不相关 Pulmonary arterial hypertension smooth muscle cell E_01_0829 Immunofluorescence staining, Western blotting, real time RT-PCR analysis In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Immunohistochemical staining In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. 免疫荧光染色，蛋白质印记，实时 RT-PCR 分析 FGF12 In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. 33336896 chr7 148804630 148806630 EZH2 RNA immunoprecipitation and RNA pull‐down results showed that lnc‐ATB positively regulated the expression of EZH2 via directly interacting with EZH2. human High+Lowthroughput Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2 不相关 cancer A2780 E_01_0830 Western blotting, real-time PCR (RT qPCR), RNA immunoprecipitation (RIP), RNA immunoprecipitation (RIP), immunohistochemistry (IHC) RNA immunoprecipitation and RNA pull‐down results showed that lnc‐ATB positively regulated the expression of EZH2 via directly interacting with EZH2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RNA immunoprecipitation and RNA pull‐down results showed that lnc‐ATB positively regulated the expression of EZH2 via directly interacting with EZH2. Immunohistochemical staining RNA immunoprecipitation and RNA pull‐down results showed that lnc‐ATB positively regulated the expression of EZH2 via directly interacting with EZH2. 蛋白质印记，实时荧光定量 PCR （RT-qPCR），RNA免疫沉淀（RIP），RNA免疫沉淀（RIP），免疫组化（IHC） EZH2 RNA immunoprecipitation and RNA pull‐down results showed that lnc‐ATB positively regulated the expression of EZH2 via directly interacting with EZH2. 33334026 chr12 55964237 55966237 CDK2 Non-alcoholic fatty liver disease (NAFLD) has a large impact on global health. At the onset of disease, NAFLD is characterized by hepatic steatosis defined by the accumulation of triglycerides stored as lipid droplets. human hepatic High+Lowthroughput Pluripotent Stem Cell-Derived Hepatocytes Phenotypic Screening Reveals Small Molecules Targeting the CDK2/4-C/EBPα/DGAT2 Pathway Preventing ER-Stress Induced Lipid Accumulation 不相关 Nonalcoholic fatty liver disease pluripotent stem cell,hepatocyte E_01_0831 Tag accumulation, staining and high content imaging, real time PCR, dendrogram – hierarchical clustering using Ward's method Non-alcoholic fatty liver disease (NAFLD) has a large impact on global health. At the onset of disease, NAFLD is characterized by hepatic steatosis defined by the accumulation of triglycerides stored as lipid droplets. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Non-alcoholic fatty liver disease (NAFLD) has a large impact on global health. At the onset of disease, NAFLD is characterized by hepatic steatosis defined by the accumulation of triglycerides stored as lipid droplets. Immunohistochemical staining Non-alcoholic fatty liver disease (NAFLD) has a large impact on global health. At the onset of disease, NAFLD is characterized by hepatic steatosis defined by the accumulation of triglycerides stored as lipid droplets. TAG积累，染色和高内涵成像，实时荧光定量 PCR，树状图–使用沃德方法的分层聚类 CDK2 Non-alcoholic fatty liver disease (NAFLD) has a large impact on global health. At the onset of disease, NAFLD is characterized by hepatic steatosis defined by the accumulation of triglycerides stored as lipid droplets. 33299054 chr12 108856762 108858762 DAO Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. human Connective tissue, lymphoid High+Lowthroughput Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles 不相关 Gastrointestinal disorders Immune cell,epithelial cell,muscle cell E_01_0832 Immunofluorescence, purification of vdao, Dao activity assay, and study of the interaction between pyridoxal-5-phosphate (PLP) and histamine Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Immunohistochemical staining Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. 免疫荧光，vDAO的纯化，DAO活性测定，吡哆醛-5-磷酸（PLP）与组胺相互作用的研究 DAO Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. 33293536 chr19 10868423 10870423 CARM1 We identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). human High+Lowthroughput Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy 不相关 fibroblast E_01_0833 GST pull down assay, in vitro methylation assay, in vitro methylation assay using 3h-sam, immunodot blot assay, immunofluorescence, luciferase assay, luciferase assay, luciferase assay, ribonucleic acid sequence analysis, chip SEQ analysis, chromosome conformation capture (3C) assay We identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Immunohistochemical staining We identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). GST下拉测定，体外甲基化测定，体外甲基化测定使用3H-SAM，免疫点印迹测定，免疫荧光，荧光素酶测定，荧光素酶测定，荧光素酶测定，核糖核酸序列分析，ChIP-seq 分析，染色体构象捕获 （3C） 测定 CARM1 We identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). 33293480 chr2 181665521 181667521 NEUROD1 Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. human Neural tissue- High+Lowthroughput NEUROD1 Intrinsically Initiates Differentiation of Induced Pluripotent Stem Cells into Neural Progenitor Cells 不相关 Neuronal progenitor,pluripotent stem cell E_01_0834 ATAC SEQ, histone chip SEQ, RNA sequencing data processing, Hi-C data processing Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Immunohistochemical staining Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. ATAC-seq，组蛋白 ChIP-seq ，RNA测序数据处理，Hi-C数据处理 NEUROD1 Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. 33292225 chr7 148804685 148806685 EZH2 We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. human High+Lowthroughput EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer 不相关 oophoroma Osteoclast E_01_0835 Immunohistochemistry, cell transfection, RNA isolation and quantification, Western blot analysis, dual luciferase reporter assay, dual luciferase reporter assay, flow cytometry We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. Immunohistochemical staining We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. 免疫组化，细胞转染，RNA 分离和定量，蛋白质印迹分析，双荧光素酶报告基因检测，双荧光素酶报告基因检测，流式细胞术 EZH2 We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. 33288562 chr7 148804232 148806232 EZH2 POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor. human connective High+Lowthroughput EZH2 Expression in Follicular Lymphoma Is Variable and Independent from the Progression of Disease Within 24 Months of First Treatment 不相关 Follicular lymphoma B cell E_01_0836 Immunohistochemistry. POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor. Immunohistochemical staining POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor. Immunohistochemistry. EZH2 POD24 is currently the most useful tool for the identification of poor outlook patients. EZH2 is crucial in FL biology, but the value of its protein expression is limited as a prognostic factor. 33281964 chr7 148804758 148806758 EZH2 The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). human High+Lowthroughput LINC00565 promotes the progression of colorectal cancer by upregulating EZH2 不相关 colorectal cancer T helper cell E_01_0837 Reverse transcription quantitative polymerase chain reaction (RT qPCR), cell transfection, Transwell migration assay, RNA immunoprecipitation (RIP) The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). Immunohistochemical staining The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). 逆转录-定量聚合酶链反应（RT-qPCR），细胞转染，透孔迁移测定，RNA免疫沉淀（RIP） EZH2 The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). 33277782 chr7 148804134 148806134 EZH2 The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. human Immunohistochem High+Lowthroughput EZH2 is a potential prognostic predictor of glioma 不相关 cancer lymphocyte E_01_0838 Quantitative real-time PCR (QRT PCR), Western blot, immunohistochemical staining The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. Immunohistochemical staining The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. 实时荧光定量 PCR （qRT-PCR），蛋白质印迹，免疫组化染色 EZH2 The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. 33275145 chr19 16352505 16354505 EPS15L1 The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. human High+Lowthroughput The landscape of long noncoding RNA-involved and tumor-specific fusions across various cancers 不相关 cancer breast cancer cell,SKBR3 cell E_01_0839 Proteomic and phosphoproteomic analysis, real-time PCR, Western blot analysis The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Immunohistochemical staining The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. 蛋白质组学和磷酸化蛋白质组学分析，实时荧光定量 PCR，蛋白质印迹分析 EPS15L1 The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. 33260349 chr2 9485612 9487612 ADAM17 Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. human Epithelial High+Lowthroughput TGF-β Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPβ Pathways 不相关 lung cancer epithelial cell of lung E_01_0840 SiRNA transfection, Western blotting, chromatin immunoprecipitation assay, RNA isolation and RT-PCR Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. Immunohistochemical staining Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. siRNA转染，蛋白质印迹，染色质免疫沉淀测定，RNA分离和RT-PCR ADAM17 Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. 33257854 chr10 112947297 112949297 TCF7L2 We also identify a stage-specific enhancer in the TCF7L2 diabetes GWAS locus that drives a transient wave of gene expression in pancreatic progenitors. human High+Lowthroughput Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation 相关 rs180988137,rs78025551,rs7903146 diabetes Pancreatic progenitor cell E_01_0841 Cell directed differentiation versus hESCs, cell directed differentiation versus hESCs, fluorescence quantitative polymerase chain reaction, sgRNA cargo, gene knockdown, GSEA functional enrichment analysis, transient transcription factor motif enrichment analysis, two wave gene analysis We also identify a stage-specific enhancer in the TCF7L2 diabetes GWAS locus that drives a transient wave of gene expression in pancreatic progenitors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also identify a stage-specific enhancer in the TCF7L2 diabetes GWAS locus that drives a transient wave of gene expression in pancreatic progenitors. Immunohistochemical staining We also identify a stage-specific enhancer in the TCF7L2 diabetes GWAS locus that drives a transient wave of gene expression in pancreatic progenitors. 细胞定向分化与hESCs，细胞定向分化与hESCs，荧光定量聚合酶链反应，sgRNA-CARGO，基因敲除 ，GSEA功能富集分析，瞬态转录因子基序富集分析，双波基因分析 TCF7L2 We also identify a stage-specific enhancer in the TCF7L2 diabetes GWAS locus that drives a transient wave of gene expression in pancreatic progenitors. 33251580 chrX 15491856 15493856 ACE2 Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. human High+Lowthroughput Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer 不相关 Cardiovascular disease Stromal vascular cell E_01_0842 RNA isolation, ACE1, ACE2, and ADAM17 regulation of adipogenesis by epicardial adipose stromal cells Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. Immunohistochemical staining Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. RNA 分离，ACE1，ACE2和ADAM17通过心外膜脂肪基质细胞的脂肪发生调节 ACE2 Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. 33251489 chrX 15491850 15493850 ACE2 To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. human High+Lowthroughput SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain 不相关 New crown Suspension cell,Olfactory single cell,Cystic cell E_01_0843 RNA SEQ, immunohistochemistry, supplementary figures To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. Immunohistochemical staining To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. RNA-seq，免疫组织化学，Supplementary Figures ACE2 To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. 33250922 chr16 31480055 31482055 SLC5A2 Familial renal glucosuria is a rare renal tubular disorder caused by SLC5A2 gene variants. human connective High+Lowthroughput Six Exonic Variants in the SLC5A2 Gene Cause Exon Skipping in a Minigene Assay 不相关 Familial renal glucosuria leukocyte E_01_0844 Amplification of slc5a2 genomic fragment, mini splicing assay, mini structure and site directed mutagenesis Familial renal glucosuria is a rare renal tubular disorder caused by SLC5A2 gene variants. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Familial renal glucosuria is a rare renal tubular disorder caused by SLC5A2 gene variants. Immunohistochemical staining Familial renal glucosuria is a rare renal tubular disorder caused by SLC5A2 gene variants. SLC5A2基因组片段的扩增，微型剪接试验，微型结构和站点导向诱变 SLC5A2 Familial renal glucosuria is a rare renal tubular disorder caused by SLC5A2 gene variants. 33247104 chr2 112827574 112829574 IL1B RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. human High+Lowthroughput Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence 不相关 be senile fibroblast,macrophage E_01_0845 Dna-fish, immunofluorescence, chip SEQ, quantitative reverse transcription polymerase chain reaction, Hi-C and capture Hi-C, chip SEQ analysis, ribonucleic acid sequence analysis RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. Immunohistochemical staining RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. DNA-FISH，免疫荧光，ChIP-seq，定量逆转录-聚合酶链反应，Hi-C 和 Capture Hi-C，ChIP-seq 分析，核糖核酸序列分析 IL1B RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. 33246552 chr16 30111578 30113578 MAPK3 We found that the schizophrenia GWAS risk variations at 16p11.2 were significantly associated with mRNA levels of multiple genes in human brain, and one of the leading eQTL genes, MAPK3, located ~200-kb away from these risk variations in the genome. human High+Lowthroughput Functional Genomics Identify a Regulatory Risk Variation rs4420550 in the 16p11.2 Schizophrenia-Associated Locus 相关 rs4420550 Schizophrenia E_01_0846 Expression quantitative trait locus analysis, identification of epigenomic features, luciferase reporter assays, chromatin conformation capture, homology directed genome editing by CRISPR / cas9 (clustered regularly interspaced short palindromic repeats / cas9), RNA sequencing, and ATAC SEQ (assay for transposase accessible chromatin using sequencing) We found that the schizophrenia GWAS risk variations at 16p11.2 were significantly associated with mRNA levels of multiple genes in human brain, and one of the leading eQTL genes, MAPK3, located ~200-kb away from these risk variations in the genome. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that the schizophrenia GWAS risk variations at 16p11.2 were significantly associated with mRNA levels of multiple genes in human brain, and one of the leading eQTL genes, MAPK3, located ~200-kb away from these risk variations in the genome. Immunohistochemical staining We found that the schizophrenia GWAS risk variations at 16p11.2 were significantly associated with mRNA levels of multiple genes in human brain, and one of the leading eQTL genes, MAPK3, located ~200-kb away from these risk variations in the genome. 表达定量性状位点分析，表观基因组特征鉴定，荧光素酶报告基因测定，染色质构象捕获，通过CRISPR / Cas9（聚集的有规律间隔的短回文重复序列/ Cas9）的同源定向基因组编辑，RNA测序和ATAC-Seq（使用测序测定转座酶可访问的染色质） MAPK3 We found that the schizophrenia GWAS risk variations at 16p11.2 were significantly associated with mRNA levels of multiple genes in human brain, and one of the leading eQTL genes, MAPK3, located ~200-kb away from these risk variations in the genome. 33246486 chr8 37692893 37694893 ZNF703 It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. human Cancer High+Lowthroughput ZNF703 promotes tumor progression in ovarian cancer by interacting with HE4 and epigenetically regulating PEA15 不相关 cancer ovarian cancer cell E_01_0847 Immunohistochemistry and immunocytochemistry, fast polymerase chain reaction, Western blot, Western blot, coimmunoprecipitation, immunofluorescence and immunofluorescence colocalization, chromatin immunoprecipitation sequencing (chip SEQ) It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. Immunohistochemical staining It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. 免疫组化和免疫细胞化学，快速聚合酶链反应，蛋白质印迹，蛋白质印迹，共免疫沉淀，免疫荧光和免疫荧光共定位，染色质免疫沉淀测序（ChIP-seq） ZNF703 It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. 33239431 chr22 23784215 23786215 SMARCB1 SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. human Cancer High+Lowthroughput Nucleoporin 210 Serves a Key Scaffold for SMARCB1 in Liver Cancer 不相关 liver cancer HCC cell E_01_0848 ShRNA infection, transient transfection, RNA extraction and reverse transcription polymerase chain reaction, chromatin immunoprecipitation assay (chip) and re chromatin, chip sequencing, chip sequencing, Western blot analysis, immunoprecipitation, faire qPCR SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. Immunohistochemical staining SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. shRNA 感染，瞬时转染，RNA 提取和逆转录聚合酶链反应，染色质免疫沉淀测定 （ChIP） 和再染色质，ChIP测序，ChIP测序，蛋白质印迹分析，免疫沉淀，FAIRE qPCR SMARCB1 SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated in liver cancer. 33234727 chr10 117470772 117472772 EMX2OS EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. human Kidney High+Lowthroughput Downregulation of enhancer RNA EMX2OS is associated with poor prognosis in kidney renal clear cell carcinoma 不相关 Renal clear cell carcinoma Renal cell E_01_0849 RT-qPCR EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. Immunohistochemical staining EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. RT-qPCR EMX2OS EMX2OS downregulation was significantly associated with higher histological grade, advanced stage, and poorer prognosis. 33224573 chr5 88714545 88716545 MEF2C Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. human Lymphoid tissue, muscle High+Lowthroughput MEF2C expression, but not absence of bi-allelic deletion of TCR gamma chains (ABD), is a predictor of patient outcome in Indian T-acute lymphoblastic leukemia 不相关 T-acute lymphoblastic leukemia T cell progenitor cell,myocyte E_01_0850 Determination of MEF2C expression Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. Immunohistochemical staining Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. MEF2C表达的测定 MEF2C Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and MEF2C (Myocyte Enhancer Factor 2C) high T-ALL. 33224311 chr7 44101749 44103749 AEBP1 Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. human Connective tissue, cancer High+Lowthroughput AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-κB Pathway 不相关 Glioblastoma fat cell,Glioblastoma cell E_01_0851 Plasmid cell transfection, real-time QRT PCR, Western blot, cell migration, invasion assays, NF- κ B activity measurements Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. Immunohistochemical staining Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. 质粒细胞转染，实时 qRT-PCR，蛋白质印迹，细胞迁移、侵袭分析，NF-κB 活性测量 AEBP1 Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. 33221539 chr12 114351443 114353443 TBX5 T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. human Musculature High+Lowthroughput Transcriptional regulation of human T-box 5 gene (TBX5) by bone- and cardiac-related transcription factors 不相关 myocyte E_01_0852 Amplification of TBX5 promoter fragments，Construction of promoter-luciferase reporter vectors ，Transcription factor expressing vectors ，Transient transfection and luciferase assays T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. Immunohistochemical staining T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. Amplification of TBX5 promoter fragments，Construction of promoter-luciferase reporter vectors ，Transcription factor expressing vectors ，Transient transfection and luciferase assays TBX5 T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. 33221504 chr1 156461106 156463106 MEF2D MEF2D-fusions have recently been identified as one of the major oncogenic drivers in precursor B-cell acute lymphoblastic leukemia (B-ALL). human lymphoid High+Lowthroughput Purification, crystallization, and X-ray diffraction analysis of myocyte enhancer factor 2D and DNA complex 不相关 acute lymphoblastic leukemia B cell E_01_0853 Electrophoretic mobility shift assays MEF2D-fusions have recently been identified as one of the major oncogenic drivers in precursor B-cell acute lymphoblastic leukemia (B-ALL). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2D-fusions have recently been identified as one of the major oncogenic drivers in precursor B-cell acute lymphoblastic leukemia (B-ALL). Immunohistochemical staining MEF2D-fusions have recently been identified as one of the major oncogenic drivers in precursor B-cell acute lymphoblastic leukemia (B-ALL). Electrophoretic mobility shift assays MEF2D MEF2D-fusions have recently been identified as one of the major oncogenic drivers in precursor B-cell acute lymphoblastic leukemia (B-ALL). 33212152 chr3 70952083 70954083 FOXP1 We prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. human High+Lowthroughput Epigenetic Alterations in Keratinocyte Carcinoma 不相关 cancer keratinocyte cell E_01_0854 ChIP-seq of Keratinocyte Carcinoma，Differentially enhancer definition，Dimensionality reduction and visualization，Gene set enrichment analysis，Transcription factor motif analysis We prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. Immunohistochemical staining We prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. ChIP-seq of Keratinocyte Carcinoma，Differentially enhancer definition，Dimensionality reduction and visualization，Gene set enrichment analysis，Transcription factor motif analysis FOXP1 We prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. 33199729 chr11 69768295 69770295 FGF4 Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. human High+Lowthroughput Gene duplication, rather than epigenetic changes, drives FGF4 overexpression in KIT/PDGFRA/SDH/RAS-P WT GIST 相关 rs3168175,rs9666584 Gastrointestinal cancers E_01_0855 Global methylation profile, target methylation analysis, Sanger sequencing Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. Immunohistochemical staining Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. 全球甲基化概况，靶标甲基化分析，桑格测序 FGF4 Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. 33199677 chr2 15937777 15939777 MYCN MYCN amplification drives one in six cases of neuroblastoma. human Nervous High+Lowthroughput Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma 不相关 Neuroblastoma neuroblast E_01_0856 RNA SEQ, chip SEQ, ATAC SEQ, fluorescence in situ hybridization MYCN amplification drives one in six cases of neuroblastoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MYCN amplification drives one in six cases of neuroblastoma. Immunohistochemical staining MYCN amplification drives one in six cases of neuroblastoma. 核糖核酸序列，ChIP-seq，ATAC-seq，荧光原位杂交 MYCN MYCN amplification drives one in six cases of neuroblastoma. 33197296 chr19 33296873 33298873 CEBPA CCAAT/enhancer-binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. human lymphoid High+Lowthroughput A regulatory element in the 3'-untranslated region of CEBPA is associated with myeloid/NK/T-cell leukemia 不相关 leukemia T cell E_01_0857 DNA methylation analysis, real time PCR, electrophoretic mobility shift assay (EMSA) CCAAT/enhancer-binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CCAAT/enhancer-binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. Immunohistochemical staining CCAAT/enhancer-binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. DNA甲基化分析，Real-time PCR，Electrophoretic mobility shift assay (EMSA) CEBPA CCAAT/enhancer-binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. 33196849 chr16 67559614 67561614 CTCF Using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. human High+Lowthroughput Generation of onco-enhancer enhances chromosomal remodeling and accelerates tumorigenesis 不相关 tumour embryonic stem cell E_01_0858 RNA extraction, library construction and Illumina sequencing (RNA SEQ) Using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. Immunohistochemical staining Using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. RNA 提取、文库构建和 Illumina 测序 （RNA-seq） CTCF Using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. 33193627 chr12 9749885 9751885 CD69 The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. human High+Lowthroughput Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression 不相关 hematopoietic cell,lymphocyte E_01_0859 Luciferase assays, crispr-cas9 deletion, RNA extraction and RT qPCR, Erna profiling by qPCR, chromatin immunoprecipitation The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. Immunohistochemical staining The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. 荧光素酶检测，CRISPR-Cas9 删除，RNA 提取和 RT-qPCR，通过 qPCR 进行 eRNA 分析，染色质免疫沉淀 CD69 The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. 33184061 chr9 70381623 70383623 KLF9 Some genes, including Krüppel-like factor 9 (KLF9), a putative transcriptional repressor, demonstrate conserved responses. human Epithelial High+Lowthroughput Genomic determinants implicated in the glucocorticoid-mediated induction of KLF9 in pulmonary epithelial cells 不相关 epithelial cell E_01_0860 RNA isolation, cDNA synthesis, and SYBR green real-time PCR Some genes, including Krüppel-like factor 9 (KLF9), a putative transcriptional repressor, demonstrate conserved responses. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Some genes, including Krüppel-like factor 9 (KLF9), a putative transcriptional repressor, demonstrate conserved responses. Immunohistochemical staining Some genes, including Krüppel-like factor 9 (KLF9), a putative transcriptional repressor, demonstrate conserved responses. RNA isolation, cDNA synthesis, and SYBR green real-time PCR KLF9 Some genes, including Krüppel-like factor 9 (KLF9), a putative transcriptional repressor, demonstrate conserved responses. 33182063 chr1 247413256 247415256 NLRP3 The findings may suggest that MyD88/NF-κB pathway is an upstream regulator of NLRP3 inflammasome underlying smoking-induced atherosclerosis. human High+Lowthroughput Molecular insights of cigarette smoke condensate-activated NLRP3 inflammasome in THP-1 cells in a stage-specific atherogenesis 不相关 Atherosclerosis THP-1 E_01_0861 Transcriptional profiling，Immunocytochemistry，Cytokine assays，qPCR array The findings may suggest that MyD88/NF-κB pathway is an upstream regulator of NLRP3 inflammasome underlying smoking-induced atherosclerosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The findings may suggest that MyD88/NF-κB pathway is an upstream regulator of NLRP3 inflammasome underlying smoking-induced atherosclerosis. Immunohistochemical staining The findings may suggest that MyD88/NF-κB pathway is an upstream regulator of NLRP3 inflammasome underlying smoking-induced atherosclerosis. Transcriptional profiling，Immunocytochemistry，Cytokine assays，qPCR array NLRP3 The findings may suggest that MyD88/NF-κB pathway is an upstream regulator of NLRP3 inflammasome underlying smoking-induced atherosclerosis. 33179113 chr18 76371869 76373869 Smad2 The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. mouse Epithelial High+Lowthroughput Activation of activin/Smad2 and 3 signaling pathway and the potential involvement of endothelial?mesenchymal transition in the valvular damage due to rheumatic heart disease 不相关 Rheumatic heart disease endothelial cell E_01_0862 Histochemistry, reverse transcription quantitative (rt-q) PCR, Western blot analysis The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. Immunohistochemical staining The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. 组织化学，逆转录定量 （RT-q） PCR，蛋白质印迹分析 Smad2 The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. 33176148 chr1 26690137 26692137 ARID1A ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. human High+Lowthroughput ARID1A Mutations Promote P300-Dependent Endometrial Invasion through Super-Enhancer Hyperacetylation 不相关 Chromatin immunoprecipitation endometrial cell E_01_0863 Histology and immunohistochemistry, cell transfection, cell viability assay, annexin V assay, chromatin immunoprecipitation ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. Immunohistochemical staining ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. 组织学和免疫组织化学，细胞转染，细胞活力测定，膜联蛋白V测定，染色质免疫沉淀 ARID1A ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. 33167400 chr7 16913285 16915285 AHR Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM2.5-mediated atherogenesis. human Lymphoid tissues, epithelial High+Lowthroughput AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis 不相关 Vascular inflammation and atherosclerosis macrophage, endothelial cell E_01_0864 RNA isolation and quantitative real-time RT-PCR (qPCR), transfection experiments and luciferase assays, gel mobility shift assay (GMSA) Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM2.5-mediated atherogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM2.5-mediated atherogenesis. Immunohistochemical staining Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM2.5-mediated atherogenesis. RNA分离和定量实时RT-PCR（qPCR），转染实验和荧光素酶测定，凝胶迁移率转移分析（GMSA） AHR Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributing to PM2.5-mediated atherogenesis. 33164433 chr9 117701684 117703684 TLR4 Its protection mechanism may be related to inhibiting TLR4 signaling pathways. human Epithelial High+Lowthroughput [Effect of baicalin on inflammatory response and TLR4/NF-κB signaling pathway of human brain microvascular endothelial cell after hypoxia-reoxygenation injury] 不相关 cerebral apoplexy microvascular endothelial cell E_01_0865 Immunofluorescence assay, Western blot Its protection mechanism may be related to inhibiting TLR4 signaling pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Its protection mechanism may be related to inhibiting TLR4 signaling pathways. Immunohistochemical staining Its protection mechanism may be related to inhibiting TLR4 signaling pathways. 免疫荧光法检测， Western blot TLR4 Its protection mechanism may be related to inhibiting TLR4 signaling pathways. 33163273 chr19 33371055 33373055 CEBPG High CEBPG expression is regulated by the ESCC specific transcription factor TP63 and serves as a prognostic factor for poor survival in ESCC patients. human cancer cell High+Lowthroughput CEBPG promotes esophageal squamous cell carcinoma progression by enhancing PI3K-AKT signaling 不相关 Esophageal squamous cell carcinoma ESCC E_01_0866 RNA extraction and QRT PCR analysis, Western blotting, siRNA and transfection, chromatin immunoprecipitation polymerase chain (chip PCR) High CEBPG expression is regulated by the ESCC specific transcription factor TP63 and serves as a prognostic factor for poor survival in ESCC patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq High CEBPG expression is regulated by the ESCC specific transcription factor TP63 and serves as a prognostic factor for poor survival in ESCC patients. Immunohistochemical staining High CEBPG expression is regulated by the ESCC specific transcription factor TP63 and serves as a prognostic factor for poor survival in ESCC patients. RNA 提取和 qRT-PCR 分析，蛋白质印记，siRNA 和转染，染色质免疫沉淀聚合酶链 （ChIP-PCR） CEBPG High CEBPG expression is regulated by the ESCC specific transcription factor TP63 and serves as a prognostic factor for poor survival in ESCC patients. 33148375 chrX 136143924 136145924 FHL1 Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. human Musculature High+Lowthroughput MiR-183-5p induced by saturated fatty acids regulates the myogenic differentiation by directly targeting FHL1 in C2C12 myoblasts 不相关 myoblast cell E_01_0867 Gene knockdown, immunofluorescence staining Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. Immunohistochemical staining Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. 基因敲降，免疫荧光染色 FHL1 Long-chain SFA palmitic acid (PA) drastically reduced myogenic transcription factors, such as myoblast determination protein (MyoD), myogenin (MyoG), and myocyte enhancer factor 2C (MEF2C), and inhibited FHL1 expression and myogenic differentiation of C2C12 myoblasts, accompanied by the induction of miR-183-5p. 33145887 chr5 138462973 138464973 EGR1 EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics. human hepatic High+Lowthroughput EGR1-mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer 不相关 gastric cancer hepatocyte E_01_0868 RT qPCR analysis, cell transfection, RNA immunoprecipitation (RIP), chromatin immunoprecipitation test (chip), subcellular fractionation, and fluorescence in situ hybridization (FISH) assay EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics. Immunohistochemical staining EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics. RT-qPCR分析，细胞转染，RNA免疫沉淀（RIP），染色质免疫沉淀测试（ChIP）,亚细胞分离和荧光原位杂交（FISH）测定 EGR1 EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics. 33137873 chr7 148804266 148806266 EZH2 β-Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. human lymphoid High+Lowthroughput Enhancer of Zeste Homolog 2 (EZH2) Mediates Glucolipotoxicity-Induced Apoptosis in β-Cells 不相关 diabetes B cell E_01_0869 Small molecule inhibitors, gene knockdown, mRNA microarray, real-time PCR, immunoblot analysis β-Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq β-Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. Immunohistochemical staining β-Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. 小分子抑制剂，基因敲降，mRNA微阵列，实时荧光定量 PCR，免疫印迹分析 EZH2 β-Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. 33134376 chr1 11931678 11933678 PLOD1 Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. human High+Lowthroughput PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma 不相关 Osteosarcoma U-2OS cell，MG-63 cell E_01_0870 Cell culture and interfering RNA transfection, Western blot analysis, RNA isolation and RT-PCR, TCF / lef luciferase reporter assay, immunofluorescence staining Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. Immunohistochemical staining Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. 细胞培养和干扰RNA转染，蛋白质印记分析，RNA分离和RT-PCR，TCF/LEF萤光素酶报告分析，免疫荧光染色 PLOD1 Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. 33129761 chr14 104766534 104768534 AKT1 The mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. human Lymphoid tissue, cancer High+Lowthroughput Su(var)3-9, Enhancer of Zeste, and Trithorax Domain-Containing 5 Facilitates Tumor Growth and Pulmonary Metastasis through Up-Regulation of AKT1 Signaling in Breast Cancer 不相关 mammary cancer macrophage，breast cancer cell E_01_0871 Cell transfection, IHC, Western blot, immunofluorescence, migration and invasion assays, semi quantitative analysis of immunostaining The mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. Immunohistochemical staining The mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. 细胞转染，IHC, western blot, immunofluorescence, migration and invasion assays，Semi-quantitative analysis of immunostaining AKT1 The mechanistic analysis showed that SETD5 contributes BC progression by interacting with AKT1 pathway. 33125094 chr2 69642193 69644193 ANXA4 Annexin IV (ANXA4) is highly expressed in ovarian clear cell carcinoma (OCCC); however, its underlying molecular mechanism in OCCC remains unknown. human Lymphoid tissue, cancer High+Lowthroughput p53 and ANXA4/NF?κB p50 complexes regulate cell proliferation, apoptosis and tumor progression in ovarian clear cell carcinoma 不相关 Ovarian clear cell carcinoma B cell，Ovarian Clear cell carcinoma E_01_0872 Immunohistochemistry, cell transfection, CO immunoprecipitation, Western blotting, flow cytometry Annexin IV (ANXA4) is highly expressed in ovarian clear cell carcinoma (OCCC); however, its underlying molecular mechanism in OCCC remains unknown. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Annexin IV (ANXA4) is highly expressed in ovarian clear cell carcinoma (OCCC); however, its underlying molecular mechanism in OCCC remains unknown. Immunohistochemical staining Annexin IV (ANXA4) is highly expressed in ovarian clear cell carcinoma (OCCC); however, its underlying molecular mechanism in OCCC remains unknown. 免疫组化，细胞转染，共免疫沉淀，蛋白质印记，流式细胞术 ANXA4 Annexin IV (ANXA4) is highly expressed in ovarian clear cell carcinoma (OCCC); however, its underlying molecular mechanism in OCCC remains unknown. 33124053 chr10 103084318 103086318 NT5C2 A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. human lymphoid High+Lowthroughput Effects of NT5C2 Germline Variants on 6-Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia 相关 rs10883841,rs12256506,rs7091462,rs12240508 acute lymphoblastic leukemia erythrocyte E_01_0873 NT5C2 recombinant protein production and 5’-nucleotidase activity assay A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. Immunohistochemical staining A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. NT5C2 recombinant protein production and 5’-nucleotidase activity assay NT5C2 A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. 33121685 chr18 40386919 40388919 Kctd16 In this study, we identified a novel gene regulatory genomic element in mouse primary spermatocytes, DES-K16, in an intron of the Kctd16 gene. mouse High+Lowthroughput A dual enhancer-silencer element, DES-K16, in mouse spermatocyte-derived GC-2spd(ts) cells 不相关 E_01_0874 Cell culture, transfection, and reporter gene assay，qRT-PCR analysis，ChIP-sequencing data analysis In this study, we identified a novel gene regulatory genomic element in mouse primary spermatocytes, DES-K16, in an intron of the Kctd16 gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we identified a novel gene regulatory genomic element in mouse primary spermatocytes, DES-K16, in an intron of the Kctd16 gene. Immunohistochemical staining In this study, we identified a novel gene regulatory genomic element in mouse primary spermatocytes, DES-K16, in an intron of the Kctd16 gene. Cell culture, transfection, and reporter gene assay，qRT-PCR analysis，ChIP-sequencing data analysis Kctd16 In this study, we identified a novel gene regulatory genomic element in mouse primary spermatocytes, DES-K16, in an intron of the Kctd16 gene. 33121524 chr7 148804652 148806652 EZH2 Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy. human Cancer High+Lowthroughput Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2 不相关 Hepatocellular carcinoma hepatocellular carcinoma cell E_01_0875 Edu assay, flow cytometry, Western blot and xenograft assay, bioinformatics analysis and quantitative polymerase chain reaction (QRT PCR), RNA immunoprecipitation (RIP), RNA pull-down assay, QRT PCR assay, luciferase reporter Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy. Immunohistochemical staining Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy. EdU测定，流式细胞术，蛋白质印迹和异种移植测定，生物信息学分析和定量聚合酶链反应（qRT-PCR），RNA免疫沉淀（RIP）、RNA下拉测定、qRT-PCR检测，荧光素酶报告 EZH2 Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy. 33116876 chr2 25730681 25732681 ASXL2 These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC. human Cancer High+Lowthroughput Elevated Expression of ASXL2 is Associated with Poor Prognosis in Colorectal Cancer by Enhancing Tumorigenesis and Inducing Cell Proliferation 不相关 colorectal cancer Human colorectal carcinoma cell E_01_0876 Quantitative real-time polymerase chain reaction (QRT PCR), Western blot analysis and immunohistochemistry (IHC) These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC. Immunohistochemical staining These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC. 定量实时聚合酶链反应（qRT-PCR）、蛋白质印迹分析和免疫组化（IHC） ASXL2 These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC. 33113374 chr16 67559229 67561229 CTCF We propose that CTCF functions as a typical insulator on inactive alleles, but facilitates transcription through enhancer-linking on active allele of MAE genes, indicating widespread allele-specific regulatory roles of CTCF. human lymphoid High+Lowthroughput CTCF-Mediated Genome Architecture Regulates the Dosage of Mitotically Stable Mono-allelic Expression of Autosomal Genes 不相关 T cell E_01_0877 Western blotting, single-molecule fluorescence in situ hybridization (smfish) We propose that CTCF functions as a typical insulator on inactive alleles, but facilitates transcription through enhancer-linking on active allele of MAE genes, indicating widespread allele-specific regulatory roles of CTCF. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We propose that CTCF functions as a typical insulator on inactive alleles, but facilitates transcription through enhancer-linking on active allele of MAE genes, indicating widespread allele-specific regulatory roles of CTCF. Immunohistochemical staining We propose that CTCF functions as a typical insulator on inactive alleles, but facilitates transcription through enhancer-linking on active allele of MAE genes, indicating widespread allele-specific regulatory roles of CTCF. 蛋白质印记，单分子荧光原位杂交（smFISH） CTCF We propose that CTCF functions as a typical insulator on inactive alleles, but facilitates transcription through enhancer-linking on active allele of MAE genes, indicating widespread allele-specific regulatory roles of CTCF. 33110425 chr1 41503769 41505769 HIVEP3 We found that HIVEP3 gene and LINC RNA are potentially correlated with femoral neck BMC. human connective High+Lowthroughput Association of HIVEP3 Gene and Lnc RNA with Femoral Neck Bone Mineral Content and Hip Geometry by Genome-Wide Association Analysis in Chinese People 相关 rs35282355,rs7071262,rs7907051,rs187172215,rs12152026 Osteoporosis you cementoblast E_01_0878 Genotype imputation, BMD, and hip geometry parameter measurements We found that HIVEP3 gene and LINC RNA are potentially correlated with femoral neck BMC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that HIVEP3 gene and LINC RNA are potentially correlated with femoral neck BMC. Immunohistochemical staining We found that HIVEP3 gene and LINC RNA are potentially correlated with femoral neck BMC. 基因型插补，BMD和髋关节几何参数测量 HIVEP3 We found that HIVEP3 gene and LINC RNA are potentially correlated with femoral neck BMC. 33099542 chr20 46005995 46007995 MMP9 Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia. human Nervous High+Lowthroughput Novel Data about Association of the Functionally Significant Polymorphisms of the MMP9 Gene with Exfoliation Glaucoma in the Caucasian Population of Central Russia 相关 rs3918242,rs3918249,rs17576,rs3787268,rs2250889,rs17577 Exfoliative glaucoma (xfg) in the central Russian Caucasian population retinal ganglion cell E_01_0879 DNA isolation and genotyping assays, functional SNPs Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia. Immunohistochemical staining Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia. DNA 分离和基因分型检测，功能性 SNP MMP9 Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59-1.68) in the Caucasian population of Central Russia. 33096543 chr2 74831227 74833227 HK2 In dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. human PTSD brain bank，DNA, DNAm, and related statistical procedures High+Lowthroughput Klotho, PTSD, and advanced epigenetic age in cortical tissue 相关 rs9315202 PTSD astrocyte,endothelial stalk cell，gitter cell ，The mural cell，nerve cell，oligodendroglia cell，erythrocyte E_01_0880 RNA sequencing, DNA emergence, dual luciferase reporter In dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. Immunohistochemical staining In dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. RNA测序，DNA出现，双荧光素酶报告 HK2 In dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. 33067396 chr3 47013497 47015497 SETD2 We demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors. human High+Lowthroughput Histone H3.3 G34 mutations promote aberrant PRC2 activity and drive tumor progression 不相关 Tumour stones mesenchymal stem cell,stromal cell,osteoblast E_01_0881 Chip SEQ analysis, histone methyltransferase (HMT) assay We demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors. Immunohistochemical staining We demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors. ChIP-Seq Analysis，组蛋白甲基转移酶（HMT）测定 SETD2 We demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors. 33055097 chr9 27532950 27534950 C9orf72 The GGGGCC hexanucleotide expansion in C9orf72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet a clear understanding of how C9 fits into the broader context of ALS/FTD pathology has remained lacking. mouse High+Lowthroughput Widespread intron retention impairs protein homeostasis in C9orf72 ALS brains 不相关 Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) HEK 293T E_01_0882 RNA SEQ, analysis of intron identity, gene ontology analysis, analysis of hnrnph clip SEQ data The GGGGCC hexanucleotide expansion in C9orf72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet a clear understanding of how C9 fits into the broader context of ALS/FTD pathology has remained lacking. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The GGGGCC hexanucleotide expansion in C9orf72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet a clear understanding of how C9 fits into the broader context of ALS/FTD pathology has remained lacking. Immunohistochemical staining The GGGGCC hexanucleotide expansion in C9orf72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet a clear understanding of how C9 fits into the broader context of ALS/FTD pathology has remained lacking. 核糖核酸序列数据，RNA-seq，内含子特性分析，基因本体分析，分析 hnRNPH CLIP-seq 数据 C9orf72 The GGGGCC hexanucleotide expansion in C9orf72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet a clear understanding of how C9 fits into the broader context of ALS/FTD pathology has remained lacking. 33051686 chr8 127732617 127734617 MYC MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. human Cancer High+Lowthroughput MYC as a driver of stochastic chromatin networks: implications for the fitness of cancer cells 不相关 cancer colon cancer cell E_01_0883 3D DNA FISH analysis MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. Immunohistochemical staining MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. 3D DNA FISH 分析 MYC MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. 33051488 chrX 31095139 31097139 DMD Dystrophin Dp71 is the smallest isoform of the DMD gene, mutations in which cause Duchenne muscular dystrophy (DMD). human High+Lowthroughput Dystrophin Dp71ab is monoclonally expressed in human satellite cells and enhances proliferation of myoblast cells 不相关 Duchenne muscular dystrophy stem cell,sarcoblast E_01_0884 MRNA analysis, protein analysis, cell proliferation assay, cell number assay Dystrophin Dp71 is the smallest isoform of the DMD gene, mutations in which cause Duchenne muscular dystrophy (DMD). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Dystrophin Dp71 is the smallest isoform of the DMD gene, mutations in which cause Duchenne muscular dystrophy (DMD). Immunohistochemical staining Dystrophin Dp71 is the smallest isoform of the DMD gene, mutations in which cause Duchenne muscular dystrophy (DMD). mRNA 分析，蛋白质分析，细胞增殖测定，细胞数测定 DMD Dystrophin Dp71 is the smallest isoform of the DMD gene, mutations in which cause Duchenne muscular dystrophy (DMD). 33048369 chr7 99753898 99755898 CYP3A4 The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. human High+Lowthroughput DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression 不相关 HepG2 cell E_01_0885 Plasmid construction，In vitro methylation，Luciferase reporter assay，Transfection and rifampicin induction，RNA isolation and real-time quantitative polymerase chain reaction (RT-qPCR) ，ChIP assay The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Immunohistochemical staining The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Plasmid construction，In vitro methylation，Luciferase reporter assay，Transfection and rifampicin induction，RNA isolation and real-time quantitative polymerase chain reaction (RT-qPCR) ，ChIP assay CYP3A4 The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. 33029258 chr16 67559853 67561853 CTCF We investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. human High+Lowthroughput eRNAs and Superenhancer lncRNAs Are Functional in Human Prostate Cancer 不相关 prostatic cancer human prostatic cancer cell E_01_0886 Microarray design, microarray analysis, data analysis, identification of Ernas and Se lncrnas, prediction of Erna target genes, functional enrichment analysis of target genes, TCGA data analysis, QRT PCR analysis, prediction of transcription factors (TFs) and construction of interaction networks, CTCF chip SEQ data analysis We investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Immunohistochemical staining We investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. 微阵列设计，微阵列分析、数据分析，eRNA和SE-lncRNA的鉴定，eRNA靶基因的预测，靶基因的功能富集分析，TCGA数据分析，qRT-PCR分析，转录因子（TF）的预测与交互网络的构建，CTCF ChIP-seq数据分析 CTCF We investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. 31467127 chr9 136491743 136493743 NOTCH1 Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. human tumour High+Lowthroughput Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. 是 Lymphocytic leukemia cancer cell E_01_0887 PCR, gel electrophoresis Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. Immunohistochemical staining Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. PCR,凝胶电泳 NOTCH1 Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. 31451355 chr16 67559754 67561754 CTCF CCCTC-binding factor (CTCF), cohesion (SMC1), and mediator (MED12) are the top three factors that have been reported as both essential for cellular functions and correlated with a specific looping interaction using chromosome conformation capture (3C) technology. human tumour High+Lowthroughput A Cohesin-Mediated Intrachromosomal Loop Drives Oncogenic ROR lncRNA to Accelerate Tumorigenesis 否 Cancer (cancer) cancer cell E_01_0888 Western blot, PCR, gel electrophoresis CCCTC-binding factor (CTCF), cohesion (SMC1), and mediator (MED12) are the top three factors that have been reported as both essential for cellular functions and correlated with a specific looping interaction using chromosome conformation capture (3C) technology. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CCCTC-binding factor (CTCF), cohesion (SMC1), and mediator (MED12) are the top three factors that have been reported as both essential for cellular functions and correlated with a specific looping interaction using chromosome conformation capture (3C) technology. Immunohistochemical staining CCCTC-binding factor (CTCF), cohesion (SMC1), and mediator (MED12) are the top three factors that have been reported as both essential for cellular functions and correlated with a specific looping interaction using chromosome conformation capture (3C) technology. Western blot,PCR,凝胶电泳 CTCF CCCTC-binding factor (CTCF), cohesion (SMC1), and mediator (MED12) are the top three factors that have been reported as both essential for cellular functions and correlated with a specific looping interaction using chromosome conformation capture (3C) technology. 31444232 chr7 55016353 55018353 EGFR Intron 1-Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins. human Epithelial High+Lowthroughput Intron 1-Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins 否 Neck squamous cell carcinoma Neck squamous epithelial cell E_01_0889 Flow cytometry, Western blot, PCR, gel electrophoresis Intron 1-Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Intron 1-Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins. Immunohistochemical staining Intron 1-Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins. 流式细胞术,Western blot,PCR,凝胶电泳 EGFR Intron 1-Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins. 31441598 chr11 18263505 18265505 SAA1 We reported earlier that the acute-phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. human tumour High+Lowthroughput Serum amyloid A1 mediates myotube atrophy via Toll-like receptors 否 Cancer (cancer) cancer cell E_01_0890 Western blot, PCR, gel electrophoresis We reported earlier that the acute-phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We reported earlier that the acute-phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. Immunohistochemical staining We reported earlier that the acute-phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. Western blot,PCR,凝胶电泳 SAA1 We reported earlier that the acute-phase protein serum amyloid A1 (SAA1) is increased and accumulates in muscle of ICUAW patients, but its relevance was unknown. 31441382 chr5 179803964 179805964 SQSTM1 SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. human Myotome High+Lowthroughput SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence 否 Alzheimer disease muscle cell E_01_0891 Knockdown, Western blot, PCR, gel electrophoresis SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. Immunohistochemical staining SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. 基因敲降,Western blot,PCR,凝胶电泳 SQSTM1 PPARGC1A SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. 31432184 chr3 38136163 38138163 MYD88 Disrupting myddosome assembly in diffuse large B?cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. human lymph High+Lowthroughput Disrupting myddosome assembly in diffuse large B?cell lymphoma cells using the MYD88 dimerization inhibitor ST2825 否 Cancer (cancer) Diffuse large B-cell lymphoma E_01_0892 Immunofluorescence staining, Western blot, PCR, gel electrophoresis Disrupting myddosome assembly in diffuse large B?cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Disrupting myddosome assembly in diffuse large B?cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. Immunohistochemical staining Disrupting myddosome assembly in diffuse large B?cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. 免疫荧光染色,Western blot,PCR,凝胶电泳 MYD88 Disrupting myddosome assembly in diffuse large B?cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. 31431927 chr4 122448607 122450607 IL2 Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells. human High+Lowthroughput Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells 否 Leukemia Jurkat cell E_01_0893 Western blot, PCR, gel electrophoresis Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells. Immunohistochemical staining Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells. Western blot,PCR,凝胶电泳 IL2 Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells. 31431802 chr3 181709285 181711285 SOX2 Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases. human Nervous High+Lowthroughput Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases 否 Neural disease (CNS disease) neural stem cell E_01_0894 ChIP-seq Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases. Immunohistochemical staining Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases. ChIP-seq SOX2 Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases. 31428587 chr5 68213148 68215148 PIK3R1 Amongst these genes, PIK3R1 encodes for regulatory subunit alpha of PI3-Kinase, p85α. human prostate High+Lowthroughput LSD1 Activates PI3K/AKT Signaling Through Regulating p85 Expression in Prostate Cancer Cells 否 Prostate disease (prostate cancer) LNCaP cell E_01_0895 RNA SEQ, chip SEQ, PCR, gel electrophoresis, Western blot Amongst these genes, PIK3R1 encodes for regulatory subunit alpha of PI3-Kinase, p85α. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Amongst these genes, PIK3R1 encodes for regulatory subunit alpha of PI3-Kinase, p85α. Immunohistochemical staining Amongst these genes, PIK3R1 encodes for regulatory subunit alpha of PI3-Kinase, p85α. RNA-seq,ChIP-seq,PCR,凝胶电泳,Western blot PIK3R1 Amongst these genes, PIK3R1 encodes for regulatory subunit alpha of PI3-Kinase, p85α. 31423206 chr7 148804518 148806518 EZH2 The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. human High+Lowthroughput Clinical significance of enhancer of zeste homolog 2 and histone deacetylases 1 and 2 expression in peripheral T-cell lymphoma 否 Other NK cell E_01_0896 The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. Immunohistochemical staining The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. HDAC2 EZH2,HDAC1 The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL.;The purpose of the present study was to investigate the clinical significance of enhancer of zeste homolog 2 (EZH2) and histone deacetylase 1 and 2 (HDAC1/2) expression in PTCL. 31422875 chr17 39401623 39403623 MED1 Dynamic DNA methylation is co-regulated with MED1 recruitment and H3K27ac level. human High+Lowthroughput Dynamic Enhancer DNA Methylation as Basis for Transcriptional and Cellular Heterogeneity of ESCs 是 Cancer (cancer) embryonic stem cell E_01_0897 Flow cytometry, gene knockdown, PCR, chip SEQ, RNA seq Dynamic DNA methylation is co-regulated with MED1 recruitment and H3K27ac level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Dynamic DNA methylation is co-regulated with MED1 recruitment and H3K27ac level. Immunohistochemical staining Dynamic DNA methylation is co-regulated with MED1 recruitment and H3K27ac level. 流式细胞术,基因敲降,PCR,ChIP-seq,RNA-seq MED1 Dynamic DNA methylation is co-regulated with MED1 recruitment and H3K27ac level. 31420918 chr2 45002618 45004618 SIX2 Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells human kidney High+Lowthroughput Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells 否 Renal cell carcinoma renal cell E_01_0898 Western blot, PCR, gel electrophoresis Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells Immunohistochemical staining Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells Western blot,PCR,凝胶电泳 SIX2 Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells 31419226 chr7 148803950 148805950 EZH2 DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations. human lymph High+Lowthroughput DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations 否 Cancer (cancer) lymphoma cell E_01_0899 PCR, gel electrophoresis DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations. Immunohistochemical staining DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations. PCR,凝胶电泳 EZH2,MYC,BCL2,BCL6 DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations.;DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations.;DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations.;DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations. 31415393 chr20 50188140 50190140 CEBPB The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. human Immune cells High+Lowthroughput Identifying crucial genes for prognosis in septic patients: Gene integration study based on PRISMA guidelines 否 Infectious disease NK cell E_01_0900 Flow cytometry The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. Immunohistochemical staining The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. 流式细胞术 CEBPB The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. 31413151 chr14 95083182 95085182 DICER1 We also observed distinct expres_x005f_x0002_sion patterns for Alu elements in specific tissue types (e.g., testis) (Supplemental Fig. S5D,E) or associated with specific factors (e.g., DICER1) (Supplemental Material). human High+Lowthroughput Genome-wide analysis of polymerase III-transcribed Alu elements suggests cell-type-specific enhancer function 否 Leukemia somatic cell E_01_0901 RNA SEQ, chip SEQ, PCR, gel electrophoresis We also observed distinct expres_x005f_x0002_sion patterns for Alu elements in specific tissue types (e.g., testis) (Supplemental Fig. S5D,E) or associated with specific factors (e.g., DICER1) (Supplemental Material). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also observed distinct expres_x005f_x0002_sion patterns for Alu elements in specific tissue types (e.g., testis) (Supplemental Fig. S5D,E) or associated with specific factors (e.g., DICER1) (Supplemental Material). Immunohistochemical staining We also observed distinct expres_x005f_x0002_sion patterns for Alu elements in specific tissue types (e.g., testis) (Supplemental Fig. S5D,E) or associated with specific factors (e.g., DICER1) (Supplemental Material). RNA-seq,ChIP-seq,PCR,凝胶电泳 DICER1 We also observed distinct expres_x005f_x0002_sion patterns for Alu elements in specific tissue types (e.g., testis) (Supplemental Fig. S5D,E) or associated with specific factors (e.g., DICER1) (Supplemental Material). 31410149 chr4 108045179 108047179 LEF1 MicroRNA-6852 suppresses glioma A172 cell proliferation and invasion by targeting LEF1. human High+Lowthroughput MicroRNA-6852 suppresses glioma A172 cell proliferation and invasion by targeting LEF1 否 Cancer (cancer) glioblastoma cell E_01_0902 PCR, gel electrophoresis MicroRNA-6852 suppresses glioma A172 cell proliferation and invasion by targeting LEF1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MicroRNA-6852 suppresses glioma A172 cell proliferation and invasion by targeting LEF1. Immunohistochemical staining MicroRNA-6852 suppresses glioma A172 cell proliferation and invasion by targeting LEF1. PCR,凝胶电泳 LEF1 MicroRNA-6852 suppresses glioma A172 cell proliferation and invasion by targeting LEF1. 31402092 chr3 133743447 133745447 TF Functional annotation was evaluated via epigenetic data, including DNase I hypersensitive sites and TF ChIP-seq binding peaks, from both ENCODE and Roadmap. human Epithelial High+Lowthroughput Identifying Putative Susceptibility Genes and Evaluating Their Associations with Somatic Mutations in Human Cancers 是 Cancer (cancer) Squamous cell E_01_0903 Chip SEQ, RNA SEQ, PCR, gel electrophoresis Functional annotation was evaluated via epigenetic data, including DNase I hypersensitive sites and TF ChIP-seq binding peaks, from both ENCODE and Roadmap. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional annotation was evaluated via epigenetic data, including DNase I hypersensitive sites and TF ChIP-seq binding peaks, from both ENCODE and Roadmap. Immunohistochemical staining Functional annotation was evaluated via epigenetic data, including DNase I hypersensitive sites and TF ChIP-seq binding peaks, from both ENCODE and Roadmap. ChIP-seq,RNA-seq,PCR,凝胶电泳 TF Functional annotation was evaluated via epigenetic data, including DNase I hypersensitive sites and TF ChIP-seq binding peaks, from both ENCODE and Roadmap. 31399571 chr9 127782971 127784971 CDK9 Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. human bone marrow High+Lowthroughput The pause-initiation limit restricts transcription activation in human cells 否 Cancer (cancer) K562 cell E_01_0904 PCR, RT qPCR, RNA SEQ, gel electrophoresis Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. Immunohistochemical staining Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. PCR,RT-qPCR,RNA-seq,凝胶电泳 CDK9 Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. 31397521 chr1 93990596 93992596 ABCA4 Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4. human kidney High+Lowthroughput Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4 是 Retinal disease HEK293T cell E_01_0905 Western blot, RT-PCR, gel electrophoresis Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4. Immunohistochemical staining Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4. Western blot,RT-PCR,凝胶电泳 ABCA4 Identification of splice defects due to noncanonical splice site or deep-intronic variants in ABCA4. 31390360 chr12 111440987 111442987 ATXN2 Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies. human Nervous High+Lowthroughput Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies 否 Neurodegenerative disease retinal ganglion cell E_01_0906 Gene knockdown, gel electrophoresis, Western blot Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies. Immunohistochemical staining Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies. 基因敲降,凝胶电泳,Western blot ATXN2 Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies. 31380279 chr7 148803898 148805898 EZH2 EZH2 Phosphorylation Promotes Self-Renewal of Glioma Stem-Like Cells Through NF-κB Methylation. human tumour High+Lowthroughput EZH2 Phosphorylation Promotes Self-Renewal of Glioma Stem-Like Cells Through NF-κB Methylation 否 Cancer (cancer) cancer cell E_01_0907 PCR, Western blot, gene knockdown, gel electrophoresis EZH2 Phosphorylation Promotes Self-Renewal of Glioma Stem-Like Cells Through NF-κB Methylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 Phosphorylation Promotes Self-Renewal of Glioma Stem-Like Cells Through NF-κB Methylation. Immunohistochemical staining EZH2 Phosphorylation Promotes Self-Renewal of Glioma Stem-Like Cells Through NF-κB Methylation. PCR,Western blot,基因敲降,凝胶电泳 MELK EZH2 Oncogenic roles of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) have been reported to play a crucial role in glioma tumorigenesis. EZH2 Phosphorylation Promotes Self-Renewal of Glioma Stem-Like Cells Through NF-κB Methylation. 31374988 chr15 99563212 99565212 MEF2A The vertebrate genes compose four distinct subfamilies designated MEF2A, -B, -C, and -D. There are multiple mef2 genes in the common carp (Cyprinus carpio). human Nervous High+Lowthroughput Common Carp mef2 Genes: Evolution and Expression 否 Other Neural crest cell E_01_0908 PCR, gel electrophoresis The vertebrate genes compose four distinct subfamilies designated MEF2A, -B, -C, and -D. There are multiple mef2 genes in the common carp (Cyprinus carpio). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The vertebrate genes compose four distinct subfamilies designated MEF2A, -B, -C, and -D. There are multiple mef2 genes in the common carp (Cyprinus carpio). Immunohistochemical staining The vertebrate genes compose four distinct subfamilies designated MEF2A, -B, -C, and -D. There are multiple mef2 genes in the common carp (Cyprinus carpio). PCR,凝胶电泳 MEF2A The vertebrate genes compose four distinct subfamilies designated MEF2A, -B, -C, and -D. There are multiple mef2 genes in the common carp (Cyprinus carpio). 31372638 chr16 67559785 67561785 CTCF A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation. human breast High+Lowthroughput A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation 否 Breast cancer (breast cancer) breast cancer cell E_01_0909 RNA SEQ, chip SEQ, flow cytometry, Western blot, PCR, gel electrophoresis A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation. Immunohistochemical staining A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation. RNA-seq,ChIP-seq,流式细胞术,Western blot,PCR,凝胶电泳 CTCF A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation. 31372457 chr17 63925228 63927228 CD79B Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes). human Myotome High+Lowthroughput Data showing atherosclerosis-associated differentially methylated regions are often at enhancers 否 Louisiana Cancer (Louisiana Cancer) Smooth muscle cell E_01_0910 RNA-seq,DNA-seq Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes). Immunohistochemical staining Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes). RNA-seq,DNA-seq CD79B SH3BP2,TBX20,SMAD3 Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes). Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes).;Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes).;Athero hypomethylated and hypermethylated DMRs as well as epigenetic and transcription profiles are described for the following genes: ACTA2, MYH10,MYH11 (SMC-associated genes); SMAD3 (a signaling gene for SMCs and other cell types); CD79B and SH3BP2(leukocyte-associated genes); and TBX20 and genes in the HOXA, HOXB, HOXC, and HOXD clusters (T-box and homeobox developmental genes). 31364785 chr20 50188097 50190097 CEBPB Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. human tumour High+Lowthroughput Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A 否 Cancer (cancer) MG‐63 cell E_01_0911 Western blot, PCR, gel electrophoresis Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. Immunohistochemical staining Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. Western blot,PCR,凝胶电泳 CLEC5A CEBPB Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A. 31364312 chr16 88640347 88642347 CYBA The second patient, with autosomal CGD, has a mutation in the donor splice site of intron 1 of CYBA that activates a cryptic donor splice site downstream in intron 1, causing the insertion of intronic sequences in the mRNA. human High+Lowthroughput Activation of cryptic splice sites in three patients with chronic granulomatous disease 否 Chronic granulomatous disease stem cell E_01_0912 PCR, flow cytometry The second patient, with autosomal CGD, has a mutation in the donor splice site of intron 1 of CYBA that activates a cryptic donor splice site downstream in intron 1, causing the insertion of intronic sequences in the mRNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The second patient, with autosomal CGD, has a mutation in the donor splice site of intron 1 of CYBA that activates a cryptic donor splice site downstream in intron 1, causing the insertion of intronic sequences in the mRNA. Immunohistochemical staining The second patient, with autosomal CGD, has a mutation in the donor splice site of intron 1 of CYBA that activates a cryptic donor splice site downstream in intron 1, causing the insertion of intronic sequences in the mRNA. PCR,流式细胞术 CYBA The second patient, with autosomal CGD, has a mutation in the donor splice site of intron 1 of CYBA that activates a cryptic donor splice site downstream in intron 1, causing the insertion of intronic sequences in the mRNA. 31361039 chr8 127732770 127734770 MYC Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. human tumour High+Lowthroughput Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction 是 Cancer (cancer) cancer cell E_01_0913 RNA SEQ, Western blot, PCR, gel electrophoresis Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. Immunohistochemical staining Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. RNA-seq,Western blot,PCR,凝胶电泳 MYC Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction. 31360115 chr13 73052103 73054103 KLF5 Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. human tumour High+Lowthroughput Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers 否 Breast cancer (breast cancer) HCC1937 cell E_01_0914 Western blot, PCR, gene knockdown, gel electrophoresis Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. Immunohistochemical staining Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. Western blot,PCR,基因敲降,凝胶电泳 KLF5 Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. 32311345 chr1 156461010 156463010 MEF2D Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. human muscle High+Lowthroughput miR-217-regulated MEF2D-HDAC5/ND6 signaling pathway participates in the oxidative stress and inflammatory response after cerebral ischemia 不相关 cerebral ischemic injury myocyte E_01_0915 ChIP-qPCR，Western blot，chromatin immunoprecipitation Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. Immunohistochemical staining Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. ChIP-qPCR，Western blot，chromatin immunoprecipitation MEF2D Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. 32308561 chr11 2880343 2882343 CDKN1C his study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. human melanoma High+Lowthroughput Long non-coding RNA GAS5 accelerates oxidative stress in melanoma cells by rescuing EZH2-mediated CDKN1C downregulation 不相关 melanoma melanoma cells E_01_0916 Fluorescence in situ hybridization,Western blot,RNA immunoprecipitation ,ChIP his study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq his study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. Immunohistochemical staining his study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. Fluorescence in situ hybridization,Western blot,RNA immunoprecipitation ,ChIP CDKN1C EZH2 his study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. his study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. 32308428 chr17 72118080 72120080 SOX9 Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain. human colon cancer High+Lowthroughput Long Non-Coding RNA LEF1-AS1 Promotes Migration, Invasion and Metastasis of Colon Cancer Cells Through miR-30-5p/SOX9 Axis 不相关 colon cancer colon cancer cell E_01_0917 Western blot,viability assay, colony formation assay, scratch wound healing assay Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain. Immunohistochemical staining Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain. Western blot,viability assay, colony formation assay, scratch wound healing assay LEF1-AS1 SOX9 Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain. Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1), a highly conserved and newly discovered long non-coding RNA, has been reported to be upregulated and correlated with poor prognosis in colon cancer, but the exact role of it remains uncertain. 32305636 chr5 149403478 149405478 CARMN The results of our study suggested that CARMN variations may affect the risk of esophageal cancer. human cancer High+Lowthroughput Genetic variations of CARMN affect risk of esophageal cancer in northwest China 相关 rs13177623,rs12654195,rs11168100,rs353303,rs353300,rs353299 esophageal cancer Esophageal cancer-promoting cell E_01_0918 The results of our study suggested that CARMN variations may affect the risk of esophageal cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results of our study suggested that CARMN variations may affect the risk of esophageal cancer. Immunohistochemical staining The results of our study suggested that CARMN variations may affect the risk of esophageal cancer. CARMN The results of our study suggested that CARMN variations may affect the risk of esophageal cancer. 32303902 chr7 148804273 148806273 EZH2 Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity. human tumor High+Lowthroughput High level of EZH2 expression is linked to high density of CD8-positive T-lymphocytes and an aggressive phenotype in renal cell carcinoma 不相关 renal cell carcinomas tumor cell E_01_0919 immunostaining Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity. immunostaining EZH2 Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity. 32286743 chr11 46853685 46855685 LRP4 Using advanced in silico prediction tools of splice-site alterations, including Alamut Visual software, we have demonstrated that the c.1048+6T>C LRP4 variant affects the native donor site and impairs an SC35 enhancer activity. human Blood High+Lowthroughput A novel biallelic splice-site variant in the LRP4 gene causes sclerosteosis 2 不相关 isolated syndactyly E_01_0920 RT-PCR, qPCR Using advanced in silico prediction tools of splice-site alterations, including Alamut Visual software, we have demonstrated that the c.1048+6T>C LRP4 variant affects the native donor site and impairs an SC35 enhancer activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using advanced in silico prediction tools of splice-site alterations, including Alamut Visual software, we have demonstrated that the c.1048+6T>C LRP4 variant affects the native donor site and impairs an SC35 enhancer activity. Immunohistochemical staining Using advanced in silico prediction tools of splice-site alterations, including Alamut Visual software, we have demonstrated that the c.1048+6T>C LRP4 variant affects the native donor site and impairs an SC35 enhancer activity. RT-PCR, qPCR LRP4 Using advanced in silico prediction tools of splice-site alterations, including Alamut Visual software, we have demonstrated that the c.1048+6T>C LRP4 variant affects the native donor site and impairs an SC35 enhancer activity. 32278790 chr4 102498878 102500878 NFKB1 To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. human High+Lowthroughput Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations 不相关 inborn error of immunity with immune dysregulation B cell E_01_0921 Western blotting To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. Immunohistochemical staining To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. Western blotting NFKB1 To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. 32271438 chr7 148804248 148806248 EZH2 EZH2 was highly expressed in glioma cells and EZH2-mediated H3K27me3 enrichment on the MEG3 promoter regulated the growth and metastasis of glioma cells by targeting miR-21-3p. It potentially provided a new therapeutic marker targeting glioma. human glioma High+Lowthroughput EZH2-mediated H3K27me3 enrichment on the lncRNA MEG3 promoter regulates the growth and metastasis of glioma cells by regulating miR-21-3p 不相关 Glioma glioma cell E_01_0922 qPCR，Western Blot，ChIP-Real-time PCR EZH2 was highly expressed in glioma cells and EZH2-mediated H3K27me3 enrichment on the MEG3 promoter regulated the growth and metastasis of glioma cells by targeting miR-21-3p. It potentially provided a new therapeutic marker targeting glioma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 was highly expressed in glioma cells and EZH2-mediated H3K27me3 enrichment on the MEG3 promoter regulated the growth and metastasis of glioma cells by targeting miR-21-3p. It potentially provided a new therapeutic marker targeting glioma. Immunohistochemical staining EZH2 was highly expressed in glioma cells and EZH2-mediated H3K27me3 enrichment on the MEG3 promoter regulated the growth and metastasis of glioma cells by targeting miR-21-3p. It potentially provided a new therapeutic marker targeting glioma. qPCR，Western Blot，ChIP-Real-time PCR EZH2 EZH2 was highly expressed in glioma cells and EZH2-mediated H3K27me3 enrichment on the MEG3 promoter regulated the growth and metastasis of glioma cells by targeting miR-21-3p. It potentially provided a new therapeutic marker targeting glioma. 32266019 chr6 3061360 3063360 RIPK1 RIPK1 regulates the survival of Human melanocytes upon endoplasmic reticulum stress human High+Lowthroughput RIPK1 regulates the survival of Human melanocytes upon endoplasmic reticulum stress 不相关 Vitiligo melanocyte E_01_0923 RT-PCR, Western blot RIPK1 regulates the survival of Human melanocytes upon endoplasmic reticulum stress Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RIPK1 regulates the survival of Human melanocytes upon endoplasmic reticulum stress Immunohistochemical staining RIPK1 regulates the survival of Human melanocytes upon endoplasmic reticulum stress RT-PCR, Western blot RIPK1 RIPK1 regulates the survival of Human melanocytes upon endoplasmic reticulum stress 32265994 chr18 55219283 55221283 TCF4 A huge array of function is played by the Wnt/β-catenin signaling pathway in development by balancing gene expression through the modulation of cell-specific DNA binding downstream effectors such as T-cell factor/lymphoid enhancer factor (TCF/LEF). human tumor High+Lowthroughput TCF 4 tumor suppressor: a molecular target in the prognosis of sporadic colorectal cancer in Humans 相关 sporadic colorectal cancer Enterocyte E_01_0924 qRT-PCR，immunohistochemistry ，western blot A huge array of function is played by the Wnt/β-catenin signaling pathway in development by balancing gene expression through the modulation of cell-specific DNA binding downstream effectors such as T-cell factor/lymphoid enhancer factor (TCF/LEF). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A huge array of function is played by the Wnt/β-catenin signaling pathway in development by balancing gene expression through the modulation of cell-specific DNA binding downstream effectors such as T-cell factor/lymphoid enhancer factor (TCF/LEF). Immunohistochemical staining A huge array of function is played by the Wnt/β-catenin signaling pathway in development by balancing gene expression through the modulation of cell-specific DNA binding downstream effectors such as T-cell factor/lymphoid enhancer factor (TCF/LEF). qRT-PCR，immunohistochemistry ，western blot TCF4 A huge array of function is played by the Wnt/β-catenin signaling pathway in development by balancing gene expression through the modulation of cell-specific DNA binding downstream effectors such as T-cell factor/lymphoid enhancer factor (TCF/LEF). 32248974 chr4 108164550 108166550 LEF1-AS1 Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. human colorectal cancer High+Lowthroughput CREB1-induced lncRNA LEF1-AS1 contributes to colorectal cancer progression via the miR-489/DIAPH1 axis 不相关 colorectal cancer Human colorectal carcinoma cell E_01_0925 Western blot,flow cytometry Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. Immunohistochemical staining Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. Western blot,flow cytometry LEF1-AS1 Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. 32242051 chr4 15960268 15962268 PROM1 H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells human fetal High+Lowthroughput H3K79me2/3 controls enhancer-promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells 不相关 leukemia Pan-cancer stem cell,leukemia cell E_01_0926 qRT-PCR,qPCR,flow cytometry,western blot,Immunofluorescence H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells Immunohistochemical staining H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells qRT-PCR,qPCR,flow cytometry,western blot,Immunofluorescence PROM1 H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells 32239644 chr6 137863759 137865759 TNFAIP3 By studying the lead expression‐modulating SNP, we uncovered an NF‐κB‐driven regulatory circuit which constrains T‐cell activation through the dynamic formation of a super‐enhancer that upregulates TNFAIP3 (A20), a key NF‐κB inhibitor. human primary High+Lowthroughput Resolving mechanisms of immune-mediated disease in primary CD4 T cells 相关 rs6759298,rs4672505,rs13001372,rs1736137 immune disease T cell E_01_0927 PCR， qPCR By studying the lead expression‐modulating SNP, we uncovered an NF‐κB‐driven regulatory circuit which constrains T‐cell activation through the dynamic formation of a super‐enhancer that upregulates TNFAIP3 (A20), a key NF‐κB inhibitor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By studying the lead expression‐modulating SNP, we uncovered an NF‐κB‐driven regulatory circuit which constrains T‐cell activation through the dynamic formation of a super‐enhancer that upregulates TNFAIP3 (A20), a key NF‐κB inhibitor. Immunohistochemical staining By studying the lead expression‐modulating SNP, we uncovered an NF‐κB‐driven regulatory circuit which constrains T‐cell activation through the dynamic formation of a super‐enhancer that upregulates TNFAIP3 (A20), a key NF‐κB inhibitor. PCR， qPCR TNFAIP3 By studying the lead expression‐modulating SNP, we uncovered an NF‐κB‐driven regulatory circuit which constrains T‐cell activation through the dynamic formation of a super‐enhancer that upregulates TNFAIP3 (A20), a key NF‐κB inhibitor. 32238924 chr19 49082627 49084627 SNRNP70 Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts,without altering the overall transcription rate in cells human High+Lowthroughput U1 snRNP regulates chromatin retention of noncoding RNAs 不相关 stem cell E_01_0928 qPCR，RT-qPCR，ChIP-qPCR，western immunoblot，Flow Cytometry Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts,without altering the overall transcription rate in cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts,without altering the overall transcription rate in cells Immunohistochemical staining Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts,without altering the overall transcription rate in cells qPCR，RT-qPCR，ChIP-qPCR，western immunoblot，Flow Cytometry SNRNP70 Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts,without altering the overall transcription rate in cells 32237968 chr6 160528481 160530481 LPA Rs76735376 is an expression quantitative trait loci for the LPA gene and could affect expression by altering enhancer activity. human liver High+Lowthroughput DNA methylation profiling identifies a high effect genetic variant for lipoprotein(a) levels 相关 rs76735376,rs76735376 E_01_0929 PCR Rs76735376 is an expression quantitative trait loci for the LPA gene and could affect expression by altering enhancer activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Rs76735376 is an expression quantitative trait loci for the LPA gene and could affect expression by altering enhancer activity. Immunohistochemical staining Rs76735376 is an expression quantitative trait loci for the LPA gene and could affect expression by altering enhancer activity. PCR LPA Rs76735376 is an expression quantitative trait loci for the LPA gene and could affect expression by altering enhancer activity. 32231199 chr5 141399891 141401891 PCDHGA9 Laser confocal techniques and western blotting revealed that PCDHGA9 inhibited the nuclear translocation of β-catenin, regulated T cell factor (TCF)/ /lymphoid enhancer factor (LEF) transcriptional activity, directly impacted the signal transmission of the TGF-β/Smad2/3 pathway, strengthened the adhesion complex, weakened the effects of TGF-β, and blocked the activation of the Wnt pathway. human cancer High+Lowthroughput PCDHGA9 represses epithelial-mesenchymal transition and metastatic potential in gastric cancer cells by reducing β-catenin transcriptional activity 不相关 Gastric cancer gastric cancer cell E_01_0930 qRT-PCR,qPCR,western blotting Laser confocal techniques and western blotting revealed that PCDHGA9 inhibited the nuclear translocation of β-catenin, regulated T cell factor (TCF)/ /lymphoid enhancer factor (LEF) transcriptional activity, directly impacted the signal transmission of the TGF-β/Smad2/3 pathway, strengthened the adhesion complex, weakened the effects of TGF-β, and blocked the activation of the Wnt pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Laser confocal techniques and western blotting revealed that PCDHGA9 inhibited the nuclear translocation of β-catenin, regulated T cell factor (TCF)/ /lymphoid enhancer factor (LEF) transcriptional activity, directly impacted the signal transmission of the TGF-β/Smad2/3 pathway, strengthened the adhesion complex, weakened the effects of TGF-β, and blocked the activation of the Wnt pathway. Immunohistochemical staining Laser confocal techniques and western blotting revealed that PCDHGA9 inhibited the nuclear translocation of β-catenin, regulated T cell factor (TCF)/ /lymphoid enhancer factor (LEF) transcriptional activity, directly impacted the signal transmission of the TGF-β/Smad2/3 pathway, strengthened the adhesion complex, weakened the effects of TGF-β, and blocked the activation of the Wnt pathway. qRT-PCR,qPCR,western blotting PCDHGA9 Laser confocal techniques and western blotting revealed that PCDHGA9 inhibited the nuclear translocation of β-catenin, regulated T cell factor (TCF)/ /lymphoid enhancer factor (LEF) transcriptional activity, directly impacted the signal transmission of the TGF-β/Smad2/3 pathway, strengthened the adhesion complex, weakened the effects of TGF-β, and blocked the activation of the Wnt pathway. 32229255 chr7 30909169 30911169 AQP1 At immunoblotting, HG or HM blunted insulin ability to activate the PI3K/AKT/eNOS pathway, which was reverted through a silencing of aquaporin 1 (AQP1) and Tonicity enhancer binding protein (TonEBP), while inducing p-P38 and pERK1/2. human endothelial High+Lowthroughput Simulated hyperglycemia impairs insulin signaling in endothelial cells through a hyperosmolar mechanism 不相关 Diabetes endothelial cell E_01_0931 Immunoblotting At immunoblotting, HG or HM blunted insulin ability to activate the PI3K/AKT/eNOS pathway, which was reverted through a silencing of aquaporin 1 (AQP1) and Tonicity enhancer binding protein (TonEBP), while inducing p-P38 and pERK1/2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq At immunoblotting, HG or HM blunted insulin ability to activate the PI3K/AKT/eNOS pathway, which was reverted through a silencing of aquaporin 1 (AQP1) and Tonicity enhancer binding protein (TonEBP), while inducing p-P38 and pERK1/2. Immunohistochemical staining At immunoblotting, HG or HM blunted insulin ability to activate the PI3K/AKT/eNOS pathway, which was reverted through a silencing of aquaporin 1 (AQP1) and Tonicity enhancer binding protein (TonEBP), while inducing p-P38 and pERK1/2. Immunoblotting AQP1 At immunoblotting, HG or HM blunted insulin ability to activate the PI3K/AKT/eNOS pathway, which was reverted through a silencing of aquaporin 1 (AQP1) and Tonicity enhancer binding protein (TonEBP), while inducing p-P38 and pERK1/2. 32226522 chr4 108045215 108047215 LEF1 Our previous studies reported that lymphoid enhancer-binding factor 1 (LEF1) was upregulated in esophageal squamous cell carcinoma (ESCC) and the positive expression of LEF1 was correlated with aberrant clinicopathological characteristics in ESCC patients. human esophageal squamous cell carcinoma High+Lowthroughput MiR-34a-5p Inhibits Proliferation, Migration, Invasion and Epithelial-mesenchymal Transition in Esophageal Squamous Cell Carcinoma by Targeting LEF1 and Inactivation of the Hippo-YAP1/TAZ Signaling Pathway 不相关 esophageal squamous cell carcinoma oesophageal squamous cell E_01_0932 qRT-PCR,Western blotting Our previous studies reported that lymphoid enhancer-binding factor 1 (LEF1) was upregulated in esophageal squamous cell carcinoma (ESCC) and the positive expression of LEF1 was correlated with aberrant clinicopathological characteristics in ESCC patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our previous studies reported that lymphoid enhancer-binding factor 1 (LEF1) was upregulated in esophageal squamous cell carcinoma (ESCC) and the positive expression of LEF1 was correlated with aberrant clinicopathological characteristics in ESCC patients. Immunohistochemical staining Our previous studies reported that lymphoid enhancer-binding factor 1 (LEF1) was upregulated in esophageal squamous cell carcinoma (ESCC) and the positive expression of LEF1 was correlated with aberrant clinicopathological characteristics in ESCC patients. qRT-PCR,Western blotting LEF1 Our previous studies reported that lymphoid enhancer-binding factor 1 (LEF1) was upregulated in esophageal squamous cell carcinoma (ESCC) and the positive expression of LEF1 was correlated with aberrant clinicopathological characteristics in ESCC patients. 32692439 chr14 95083486 95085486 DICER1 Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant human brain High+Lowthroughput Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant 不相关 Primary intracranial sarcoma E_01_0933 Immunohistochemistry Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant Immunohistochemical staining Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant Immunohistochemistry DICER1 Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant 32680982 chr6 34534982 34536982 SPDEF Enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. human cancer High+Lowthroughput A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer 不相关 prostate cancer prostate cancer cell E_01_0934 q-RT PCR, ChIP-qPCRs Enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. Immunohistochemical staining Enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. q-RT PCR, ChIP-qPCRs SPDEF Enhancer with the risk allele gains response to androgen stimulation by recruiting the transcription factor SPDEF whereas, non-risk alleles remain non-responsive. 32677466 chr12 7785139 7787139 NANOG Intersecting NPC core enhancers with TFBSs predicted by Homer [25] revealed 13 transcription factors significantly enriched (q < 0.01 and >20% enhancers with motif ) (Supplementary Figure 2), including the master regulators of pluripotency NANOG and SOX3, as well as key regulators of brain development such as LHX3, a transcription factor involved in the specification of motor neurons and interneurons human brain High+Lowthroughput Epigenomic programming in early fetal brain development 相关 neural progenitor cell E_01_0935 MeDIP-seq,RNA-seq,miRNA-seq Intersecting NPC core enhancers with TFBSs predicted by Homer [25] revealed 13 transcription factors significantly enriched (q < 0.01 and >20% enhancers with motif ) (Supplementary Figure 2), including the master regulators of pluripotency NANOG and SOX3, as well as key regulators of brain development such as LHX3, a transcription factor involved in the specification of motor neurons and interneurons Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Intersecting NPC core enhancers with TFBSs predicted by Homer [25] revealed 13 transcription factors significantly enriched (q < 0.01 and >20% enhancers with motif ) (Supplementary Figure 2), including the master regulators of pluripotency NANOG and SOX3, as well as key regulators of brain development such as LHX3, a transcription factor involved in the specification of motor neurons and interneurons Immunohistochemical staining Intersecting NPC core enhancers with TFBSs predicted by Homer [25] revealed 13 transcription factors significantly enriched (q < 0.01 and >20% enhancers with motif ) (Supplementary Figure 2), including the master regulators of pluripotency NANOG and SOX3, as well as key regulators of brain development such as LHX3, a transcription factor involved in the specification of motor neurons and interneurons MeDIP-seq,RNA-seq,miRNA-seq NANOG SOX3 Intersecting NPC core enhancers with TFBSs predicted by Homer [25] revealed 13 transcription factors significantly enriched (q < 0.01 and >20% enhancers with motif ) (Supplementary Figure 2), including the master regulators of pluripotency NANOG and SOX3, as well as key regulators of brain development such as LHX3, a transcription factor involved in the specification of motor neurons and interneurons Intersecting NPC core enhancers with TFBSs predicted by Homer [25] revealed 13 transcription factors significantly enriched (q < 0.01 and >20% enhancers with motif ) (Supplementary Figure 2), including the master regulators of pluripotency NANOG and SOX3, as well as key regulators of brain development such as LHX3, a transcription factor involved in the specification of motor neurons and interneurons 32674144 chr7 148804895 148806895 EZH2 Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma human brain High+Lowthroughput Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma 不相关 Brainstem Tumor stem cell E_01_0936 Immunoblot,Immunohistochemistry Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma Immunohistochemical staining Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma Immunoblot,Immunohistochemistry EZH2 Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma 32673938 chr5 143275121 143277121 NR3C1 DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5′ regulatory region, 5 CpGs located in FKBP5 intron 7, andadditional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. human brain High+Lowthroughput Targeted bisulfite sequencing: A novel tool for the assessment of DNA methylation with high sensitivity and increased coverage 相关 rs114435510,rs75975944,rs7636061 mucosal cell E_01_0937 PCR DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5′ regulatory region, 5 CpGs located in FKBP5 intron 7, andadditional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5′ regulatory region, 5 CpGs located in FKBP5 intron 7, andadditional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. Immunohistochemical staining DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5′ regulatory region, 5 CpGs located in FKBP5 intron 7, andadditional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. PCR FKBP5 NR3C1 DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5′ regulatory region, 5 CpGs located in FKBP5 intron 7, andadditional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5′ regulatory region, 5 CpGs located in FKBP5 intron 7, andadditional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. 32673756 chr12 57513827 57515827 DDIT3 Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. human High+Lowthroughput Phosphorylation within the bipartite NLS alters the localization and toxicity of the ER stress response factor DDIT3/CHOP 不相关 E_01_0938 Western blotting Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. Immunohistochemical staining Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. Western blotting DDIT3 Commonly associated with endoplasmic reticulum stress, the bZIP transcription factor CCAAT/enhancer-binding protein homologous protein (CHOP/DDIT3) mediates the cellular response to redox stress with effects on cellular growth, differentiation, and survival. 32670558 chr3 47411003 47413003 SCAP 3MC induces the expression of PSA, SCAP, and FKBP51 genes in LNCaP and T47D cells. human High+Lowthroughput An androgen-independent mechanism underlying the androgenic effects of 3-methylcholanthrene, a potent aryl hydrocarbon receptor agonist 不相关 T47D cell E_01_0939 RT-PCR,Western blotting,Chromatin immunoprecipitation 3MC induces the expression of PSA, SCAP, and FKBP51 genes in LNCaP and T47D cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq 3MC induces the expression of PSA, SCAP, and FKBP51 genes in LNCaP and T47D cells. Immunohistochemical staining 3MC induces the expression of PSA, SCAP, and FKBP51 genes in LNCaP and T47D cells. RT-PCR,Western blotting,Chromatin immunoprecipitation SCAP 3MC induces the expression of PSA, SCAP, and FKBP51 genes in LNCaP and T47D cells. 32668391 chr1 153658780 153660780 ILF2 We found that AK085865 specifically in_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teracts with interleukin enhancer-binding factor 2 (ILF2) and facilitates M2 macrophage polarization by functioning as a negative regulator in the ILF2-ILF3 complex-mediated micro_x0002_RNA (miRNA or miR) processing pathway. human heart High+Lowthroughput lncRNA AK085865 Promotes Macrophage M2 Polarization in CVB3-Induced VM by Regulating ILF2-ILF3 Complex-Mediated miRNA-192 Biogenesis 不相关 myocarditis inflammatory cell E_01_0940 qRT-PCR，western blot We found that AK085865 specifically in_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teracts with interleukin enhancer-binding factor 2 (ILF2) and facilitates M2 macrophage polarization by functioning as a negative regulator in the ILF2-ILF3 complex-mediated micro_x0002_RNA (miRNA or miR) processing pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that AK085865 specifically in_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teracts with interleukin enhancer-binding factor 2 (ILF2) and facilitates M2 macrophage polarization by functioning as a negative regulator in the ILF2-ILF3 complex-mediated micro_x0002_RNA (miRNA or miR) processing pathway. Immunohistochemical staining We found that AK085865 specifically in_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teracts with interleukin enhancer-binding factor 2 (ILF2) and facilitates M2 macrophage polarization by functioning as a negative regulator in the ILF2-ILF3 complex-mediated micro_x0002_RNA (miRNA or miR) processing pathway. qRT-PCR，western blot ILF2 We found that AK085865 specifically in_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teracts with interleukin enhancer-binding factor 2 (ILF2) and facilitates M2 macrophage polarization by functioning as a negative regulator in the ILF2-ILF3 complex-mediated micro_x0002_RNA (miRNA or miR) processing pathway. 32663239 chr10 73906377 73908377 PLAU We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). human non-neuronal solid High+Lowthroughput Enhancer-gene rewiring in the pathogenesis of Quebec platelet disorder 相关 rs1916341 Quebec Platelet Disorder dendritic cell E_01_0941 ChIP-seq We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). Immunohistochemical staining We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). ChIP-seq PLAU We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). 32661323 chr8 47734489 47736489 CEBPD Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer human sample High+Lowthroughput Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer 不相关 cervical cancer cervical cancer cells E_01_0942 qPCR,Immunohistochemistry,Western blotting Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer Immunohistochemical staining Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer qPCR,Immunohistochemistry,Western blotting CEBPD Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer 32660626 chr8 101489497 101491497 GRHL2 Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. human gastric High+Lowthroughput M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade 不相关 gastric cancer vein endothelial cell E_01_0943 chromatin immunoprecipitation Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. Immunohistochemical staining Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. chromatin immunoprecipitation GRHL2 Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. 32659776 chr2 135784821 135786821 LCT Polymorphisms in the enhancer of the lactase gene (LCT) are strongly associated with lactase per_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_sistence, but not always predictive of the phenotype. human High+Lowthroughput Lack of Association between LCT_rs140433552*CA>del Indel Polymorphism and Lactose Intolerance in a Southern Brazilian Population 不相关 rs4988235,rs140433552,rs140433552 Lactose Intolerance E_01_0944 PCR Polymorphisms in the enhancer of the lactase gene (LCT) are strongly associated with lactase per_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_sistence, but not always predictive of the phenotype. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Polymorphisms in the enhancer of the lactase gene (LCT) are strongly associated with lactase per_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_sistence, but not always predictive of the phenotype. Immunohistochemical staining Polymorphisms in the enhancer of the lactase gene (LCT) are strongly associated with lactase per_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_sistence, but not always predictive of the phenotype. PCR LCT Polymorphisms in the enhancer of the lactase gene (LCT) are strongly associated with lactase per_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_sistence, but not always predictive of the phenotype. 32659720 chr4 38661436 38663436 KLF3 Over half of KLF3’s genomic binding sites occur at active enhancers.KLF3 binds to active enhancers proximal to differentiation genes that are depen_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_dent upon KLF3 for expression. human epithelial High+Lowthroughput KLF3 Mediates Epidermal Differentiation through the Epigenomic Writer CBP 不相关 skin diseases progenitor cell E_01_0945 RT-qPCR,Western blot Over half of KLF3’s genomic binding sites occur at active enhancers.KLF3 binds to active enhancers proximal to differentiation genes that are depen_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_dent upon KLF3 for expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Over half of KLF3’s genomic binding sites occur at active enhancers.KLF3 binds to active enhancers proximal to differentiation genes that are depen_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_dent upon KLF3 for expression. Immunohistochemical staining Over half of KLF3’s genomic binding sites occur at active enhancers.KLF3 binds to active enhancers proximal to differentiation genes that are depen_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_dent upon KLF3 for expression. RT-qPCR,Western blot KLF3 Over half of KLF3’s genomic binding sites occur at active enhancers.KLF3 binds to active enhancers proximal to differentiation genes that are depen_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_dent upon KLF3 for expression. 32657761 chr7 148804541 148806541 EZH2 This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40(STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. human skin High+Lowthroughput EZH2-mediated inhibition of microRNA-22 promotes differentiation of hair follicle stem cells by elevating STK40 expression 不相关 Hair Follicle Stem Cell E_01_0946 Flow cytometry,Immunofluorescence,Western blot,RT-qPCR This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40(STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40(STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. Immunohistochemical staining This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40(STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. Flow cytometry,Immunofluorescence,Western blot,RT-qPCR EZH2 This study proposed a potential target, enhancer of zeste homolog 2 (EZH2) for facilitating hair growth, due to its function over HFSC activities by mediating the miR-22/serine/threonine kinase 40(STK40)/myocyte enhancer factor 2 (MEF2)/alkaline phosphatase (ALP) axis. 32655542 chr7 148804032 148806032 EZH2 The enhancer of zeste homolog 2 (EZH2) promoter activity was evaluated in the presence of miR-200a by dual luciferase reporter gene assay. human aorta High+Lowthroughput MicroRNA-200a Inhibits Inflammation and Atherosclerotic Lesion Formation by Disrupting EZH2-Mediated Methylation of STAT3 不相关 Inflammation and Atherosclerotic monocyte cells E_01_0947 Western Blot,Immunoprecipitation,Immunohistochemistry The enhancer of zeste homolog 2 (EZH2) promoter activity was evaluated in the presence of miR-200a by dual luciferase reporter gene assay. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The enhancer of zeste homolog 2 (EZH2) promoter activity was evaluated in the presence of miR-200a by dual luciferase reporter gene assay. Immunohistochemical staining The enhancer of zeste homolog 2 (EZH2) promoter activity was evaluated in the presence of miR-200a by dual luciferase reporter gene assay. Western Blot,Immunoprecipitation,Immunohistochemistry EZH2 The enhancer of zeste homolog 2 (EZH2) promoter activity was evaluated in the presence of miR-200a by dual luciferase reporter gene assay. 32655015 chr19 55425893 55427893 SHISA7 Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3’ UTR of SHISA7 human High+Lowthroughput Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3' UTR of SHISA7 不相关 E_01_0948 Q-PCR Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3’ UTR of SHISA7 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3’ UTR of SHISA7 Immunohistochemical staining Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3’ UTR of SHISA7 Q-PCR SHISA7 Enhancer Function of MicroRNA-3681 Derived from Long Terminal Repeats Represses the Activity of Variable Number Tandem Repeats in the 3’ UTR of SHISA7 32654217 chr8 56158114 56160114 PLAG1 These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. human tumor High+Lowthroughput Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB 不相关 pleomorphic adenoma tumor cell E_01_0949 RT-PCR These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. Immunohistochemical staining These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. RT-PCR PLAG1,HMGA2 These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2.;These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. 32654106 chr11 102108307 102110307 YAP1 Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confrm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. human ovarian cancer High+Lowthroughput MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway 不相关 ovarian cancer ovarian cancer cell E_01_0950 RT-PCR,Western blot,Immunoprecipitation Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confrm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confrm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. Immunohistochemical staining Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confrm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. RT-PCR,Western blot,Immunoprecipitation YAP1 Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confrm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. 32649979 chr7 27097694 27099694 HOXA2 Using dual luciferase reporter assays,we showed that both HOXA2 mutations have impaired activation of the long-range enhancer of HMX1. human BA2-derived High+Lowthroughput Identification of loss-of-function HOXA2 mutations in Chinese families with dominant bilateral microtia 不相关 bilateral microtia neural crest cell E_01_0951 PCR Using dual luciferase reporter assays,we showed that both HOXA2 mutations have impaired activation of the long-range enhancer of HMX1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using dual luciferase reporter assays,we showed that both HOXA2 mutations have impaired activation of the long-range enhancer of HMX1. Immunohistochemical staining Using dual luciferase reporter assays,we showed that both HOXA2 mutations have impaired activation of the long-range enhancer of HMX1. PCR HMX1 HOXA2 Using dual luciferase reporter assays,we showed that both HOXA2 mutations have impaired activation of the long-range enhancer of HMX1. Using dual luciferase reporter assays,we showed that both HOXA2 mutations have impaired activation of the long-range enhancer of HMX1. 32649856 chrX 48783413 48785413 GATA1 We identified a single sentinel variant in the GRK5 locus (rs10886430-G, p ¼ 3.0 3 10_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ 42) associated with increased thrombin induced platelet aggregation (b ¼ 0.70, SE ¼ 0.05). We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhanced platelet reactivity. The proposed mechanism of a GATA1-driven megakaryocyte enhancer is confirmed in allele-specific exper_x0002_iments. human Genotype-Tissue High+Lowthroughput A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling 不相关 pulmonary embolism E_01_0952 qRT-PCR We identified a single sentinel variant in the GRK5 locus (rs10886430-G, p ¼ 3.0 3 10_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ 42) associated with increased thrombin induced platelet aggregation (b ¼ 0.70, SE ¼ 0.05). We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhanced platelet reactivity. The proposed mechanism of a GATA1-driven megakaryocyte enhancer is confirmed in allele-specific exper_x0002_iments. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified a single sentinel variant in the GRK5 locus (rs10886430-G, p ¼ 3.0 3 10_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ 42) associated with increased thrombin induced platelet aggregation (b ¼ 0.70, SE ¼ 0.05). We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhanced platelet reactivity. The proposed mechanism of a GATA1-driven megakaryocyte enhancer is confirmed in allele-specific exper_x0002_iments. Immunohistochemical staining We identified a single sentinel variant in the GRK5 locus (rs10886430-G, p ¼ 3.0 3 10_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ 42) associated with increased thrombin induced platelet aggregation (b ¼ 0.70, SE ¼ 0.05). We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhanced platelet reactivity. The proposed mechanism of a GATA1-driven megakaryocyte enhancer is confirmed in allele-specific exper_x0002_iments. qRT-PCR GRK5 GATA1 We identified a single sentinel variant in the GRK5 locus (rs10886430-G, p ¼ 3.0 3 10_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ 42) associated with increased thrombin induced platelet aggregation (b ¼ 0.70, SE ¼ 0.05). We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhanced platelet reactivity. The proposed mechanism of a GATA1-driven megakaryocyte enhancer is confirmed in allele-specific exper_x0002_iments. We identified a single sentinel variant in the GRK5 locus (rs10886430-G, p ¼ 3.0 3 10_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ 42) associated with increased thrombin induced platelet aggregation (b ¼ 0.70, SE ¼ 0.05). We show that disruption of platelet GRK5 expression by rs10886430-G is associated with enhanced platelet reactivity. The proposed mechanism of a GATA1-driven megakaryocyte enhancer is confirmed in allele-specific exper_x0002_iments. 32641411 chr3 138941350 138943350 FOXL2 This binding induced an enhancer-like chromatin state, leading to transcription of nearby genes, many of which are characteristic of epithelial-to_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_mesenchymal transition. FOXL2C134W also bound hybrid loci in primary AGCT. human tumor High+Lowthroughput Mutant FOXL2(C134W) Hijacks SMAD4 and SMAD2/3 to Drive Adult Granulosa Cell Tumors 不相关 Granulosa Cell Tumors Ovarian granulosa cell E_01_0953 ChIP-seq，RNA-seq This binding induced an enhancer-like chromatin state, leading to transcription of nearby genes, many of which are characteristic of epithelial-to_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_mesenchymal transition. FOXL2C134W also bound hybrid loci in primary AGCT. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This binding induced an enhancer-like chromatin state, leading to transcription of nearby genes, many of which are characteristic of epithelial-to_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_mesenchymal transition. FOXL2C134W also bound hybrid loci in primary AGCT. Immunohistochemical staining This binding induced an enhancer-like chromatin state, leading to transcription of nearby genes, many of which are characteristic of epithelial-to_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_mesenchymal transition. FOXL2C134W also bound hybrid loci in primary AGCT. ChIP-seq，RNA-seq FOXL2 This binding induced an enhancer-like chromatin state, leading to transcription of nearby genes, many of which are characteristic of epithelial-to_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_mesenchymal transition. FOXL2C134W also bound hybrid loci in primary AGCT. 32636391 chr17 42310887 42312887 STAT3 We identify key transcription factors including HNF4A, GR,STAT3 and STAT5, which show specific binding at enhancer and super enhancer sites,revealing enhancer dynamics and transcriptional changes during kidney repair. human kidney High+Lowthroughput Enhancer and super-enhancer dynamics in repair after ischemic acute kidney injury 不相关 kidney disease tubular epithelial cell E_01_0954 ChIP-seq,RNA-seq We identify key transcription factors including HNF4A, GR,STAT3 and STAT5, which show specific binding at enhancer and super enhancer sites,revealing enhancer dynamics and transcriptional changes during kidney repair. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identify key transcription factors including HNF4A, GR,STAT3 and STAT5, which show specific binding at enhancer and super enhancer sites,revealing enhancer dynamics and transcriptional changes during kidney repair. Immunohistochemical staining We identify key transcription factors including HNF4A, GR,STAT3 and STAT5, which show specific binding at enhancer and super enhancer sites,revealing enhancer dynamics and transcriptional changes during kidney repair. ChIP-seq,RNA-seq STAT3 We identify key transcription factors including HNF4A, GR,STAT3 and STAT5, which show specific binding at enhancer and super enhancer sites,revealing enhancer dynamics and transcriptional changes during kidney repair. 32635336 chr7 148804321 148806321 EZH2 Enhancer of zeste homolog 2(EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. human Glioblastoma High+Lowthroughput Epigenetic Silencing of miR-9 Promotes Migration and Invasion by EZH2 in Glioblastoma Cells 不相关 Glioblastoma glioblastoma cell E_01_0955 qRT-PCR,Chromatin Immunoprecipitation,Western Blot Enhancer of zeste homolog 2(EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2(EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. Immunohistochemical staining Enhancer of zeste homolog 2(EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. qRT-PCR,Chromatin Immunoprecipitation,Western Blot EZH2,CXCR4 Enhancer of zeste homolog 2(EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized.;Enhancer of zeste homolog 2(EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. 32634265 chr7 148804399 148806399 EZH2 HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β-catenin signaling. human osteosarcoma High+Lowthroughput The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-catenin cascade promotes malignant and metastatic progression of osteosarcoma 不相关 osteosarcoma mesenchymal stem cell E_01_0956 RT-PCR,Western blot HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β-catenin signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β-catenin signaling. Immunohistochemical staining HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β-catenin signaling. RT-PCR,Western blot EZH2 HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β-catenin signaling. 32633375 chr4 108045078 108047078 LEF1 The expression of miR-381 and LEF1 (lymphoid enhancer-bind_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ing factor-1) was quantified using quantitative Real Time-Polymerase Chain Reaction (qRT_x0002_PCR) and Western blot analysis. human High+Lowthroughput MicroRNA-381 inhibits metastasis and epithelial-mesenchymal transition of glioblastoma cells through targeting LEF1 不相关 Glioblastoma glioblastoma cell E_01_0957 qRT-PCR,Western blot The expression of miR-381 and LEF1 (lymphoid enhancer-bind_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ing factor-1) was quantified using quantitative Real Time-Polymerase Chain Reaction (qRT_x0002_PCR) and Western blot analysis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression of miR-381 and LEF1 (lymphoid enhancer-bind_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ing factor-1) was quantified using quantitative Real Time-Polymerase Chain Reaction (qRT_x0002_PCR) and Western blot analysis. Immunohistochemical staining The expression of miR-381 and LEF1 (lymphoid enhancer-bind_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ing factor-1) was quantified using quantitative Real Time-Polymerase Chain Reaction (qRT_x0002_PCR) and Western blot analysis. qRT-PCR,Western blot LEF1 The expression of miR-381 and LEF1 (lymphoid enhancer-bind_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ing factor-1) was quantified using quantitative Real Time-Polymerase Chain Reaction (qRT_x0002_PCR) and Western blot analysis. 32633341 chr7 148804242 148806242 EZH2 Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target pro_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teins were analyzed by RNA co-precipitation exper_x0002_iments. human osteosarcoma High+Lowthroughput Circ100284 promotes invasion and migration of osteosarcoma cells by down-regulating PTEN and EMP1 不相关 osteosarcoma osteosarcoma cell E_01_0958 qRT-PCR,Western Blotting Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target pro_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teins were analyzed by RNA co-precipitation exper_x0002_iments. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target pro_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teins were analyzed by RNA co-precipitation exper_x0002_iments. Immunohistochemical staining Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target pro_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teins were analyzed by RNA co-precipitation exper_x0002_iments. qRT-PCR,Western Blotting EZH2 Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target pro_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_teins were analyzed by RNA co-precipitation exper_x0002_iments. 32632701 chr6 45325376 45327376 RUNX2 The signifcant loss of chondrocytes in grades 2 and 3 of LFJs was observed. The expression levels of CCAAT enhancer binding protein β (C/EBPβ), Runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP13) also increased with the aggravation of degeneration (4.89, 5.77, and 6.3 times by Western blot). human cartilage High+Lowthroughput Interaction between C/EBPβ and RUNX2 promotes apoptosis of chondrocytes during Human lumbar facet joint degeneration 不相关 arthritis neuroblast E_01_0959 Flow cytometry,Western blot The signifcant loss of chondrocytes in grades 2 and 3 of LFJs was observed. The expression levels of CCAAT enhancer binding protein β (C/EBPβ), Runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP13) also increased with the aggravation of degeneration (4.89, 5.77, and 6.3 times by Western blot). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The signifcant loss of chondrocytes in grades 2 and 3 of LFJs was observed. The expression levels of CCAAT enhancer binding protein β (C/EBPβ), Runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP13) also increased with the aggravation of degeneration (4.89, 5.77, and 6.3 times by Western blot). Immunohistochemical staining The signifcant loss of chondrocytes in grades 2 and 3 of LFJs was observed. The expression levels of CCAAT enhancer binding protein β (C/EBPβ), Runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP13) also increased with the aggravation of degeneration (4.89, 5.77, and 6.3 times by Western blot). Flow cytometry,Western blot RUNX2 The signifcant loss of chondrocytes in grades 2 and 3 of LFJs was observed. The expression levels of CCAAT enhancer binding protein β (C/EBPβ), Runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP13) also increased with the aggravation of degeneration (4.89, 5.77, and 6.3 times by Western blot). 32632335 chr11 33856049 33858049 LMO2 For example, cis-X identified both ABTB2 and TMEM38B as cis-activated by structural variants; however, both genes were adjacent to known proto-oncogenes in the same TAD (LMO2 and TAL2, respectively); thus, they were potentially coregu_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_lated by an aberrant enhancer. human High+Lowthroughput Discovery of regulatory noncoding variants in individual cancer genomes by using cis-X 不相关 leukemia tumor cell E_01_0960 RNA-seq,ChIP–seq For example, cis-X identified both ABTB2 and TMEM38B as cis-activated by structural variants; however, both genes were adjacent to known proto-oncogenes in the same TAD (LMO2 and TAL2, respectively); thus, they were potentially coregu_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_lated by an aberrant enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For example, cis-X identified both ABTB2 and TMEM38B as cis-activated by structural variants; however, both genes were adjacent to known proto-oncogenes in the same TAD (LMO2 and TAL2, respectively); thus, they were potentially coregu_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_lated by an aberrant enhancer. Immunohistochemical staining For example, cis-X identified both ABTB2 and TMEM38B as cis-activated by structural variants; however, both genes were adjacent to known proto-oncogenes in the same TAD (LMO2 and TAL2, respectively); thus, they were potentially coregu_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_lated by an aberrant enhancer. RNA-seq,ChIP–seq LMO2,TAL2 For example, cis-X identified both ABTB2 and TMEM38B as cis-activated by structural variants; however, both genes were adjacent to known proto-oncogenes in the same TAD (LMO2 and TAL2, respectively); thus, they were potentially coregu_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_lated by an aberrant enhancer.;For example, cis-X identified both ABTB2 and TMEM38B as cis-activated by structural variants; however, both genes were adjacent to known proto-oncogenes in the same TAD (LMO2 and TAL2, respectively); thus, they were potentially coregu_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_lated by an aberrant enhancer. 32631994 chr7 148804082 148806082 EZH2 Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), which minimally requires two other subunits, EED and SUZ12, for enzymatic activity. human High+Lowthroughput A partially disordered region connects gene repression and activation functions of EZH2 不相关 cancer cell E_01_0961 RT-PCR Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), which minimally requires two other subunits, EED and SUZ12, for enzymatic activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), which minimally requires two other subunits, EED and SUZ12, for enzymatic activity. Immunohistochemical staining Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), which minimally requires two other subunits, EED and SUZ12, for enzymatic activity. RT-PCR EZH2 Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), which minimally requires two other subunits, EED and SUZ12, for enzymatic activity. 33084547 chr14 100235938 100237938 YY1 We also confirmed that cellular transcription factor Yin-Yang 1 (YY1) and viral protein HBx mediated the spatial regulation of HBV cccDNA transcription by 19p13.11 enhancer. human liver High+Lowthroughput Yin-Yang 1 and HBx protein activate HBV transcription by mediating the spatial interaction of cccDNA minichromosome with cellular chromosome 19p13.11 不相关 liver cancer HCC cell E_01_0962 PCR,western blots We also confirmed that cellular transcription factor Yin-Yang 1 (YY1) and viral protein HBx mediated the spatial regulation of HBV cccDNA transcription by 19p13.11 enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also confirmed that cellular transcription factor Yin-Yang 1 (YY1) and viral protein HBx mediated the spatial regulation of HBV cccDNA transcription by 19p13.11 enhancer. Immunohistochemical staining We also confirmed that cellular transcription factor Yin-Yang 1 (YY1) and viral protein HBx mediated the spatial regulation of HBV cccDNA transcription by 19p13.11 enhancer. PCR,western blots YY1 We also confirmed that cellular transcription factor Yin-Yang 1 (YY1) and viral protein HBx mediated the spatial regulation of HBV cccDNA transcription by 19p13.11 enhancer. 33070167 chr1 202005474 202007474 ELF3 human High+Lowthroughput Aberrant super-enhancer landscape reveals core transcriptional regulatory circuitry in lung adenocarcinoma 不相关 Lung adenocarcinoma E_01_0963 ChIP-qPCR,western blot Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Immunohistochemical staining ChIP-qPCR,western blot ELF3,EHF,TGIF1 33062456 chr1 91677376 91679376 TGFBR3 Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling,significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B,SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. human High+Lowthroughput Hyaluronic acid ameliorates the proliferative ability of Human amniotic epithelial cells through activation of TGF-β/BMP signaling 不相关 E_01_0964 RT-qPCR Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling,significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B,SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling,significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B,SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. Immunohistochemical staining Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling,significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B,SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. RT-qPCR TGFBR3 SMAD3 Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling,significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B,SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. Further study showed that SB431542, an inhibitor of the TGF-β/BMP signaling,significantly suppressed the mRNA expression of TGFBR3, BMP4, BMP7, BMPR1B,SMAD3, SMAD4, and the pro-proliferative effect of HA on hAECs. 33061937 chr13 48301408 48303408 RB1 The present study analyses the regulatory activity of a Human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. human High+Lowthroughput An Intronic Alu Element Attenuates the Transcription of a Long Non-coding RNA in Human Cell Lines 不相关 K562 cell E_01_0965 PCR The present study analyses the regulatory activity of a Human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study analyses the regulatory activity of a Human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. Immunohistochemical staining The present study analyses the regulatory activity of a Human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. PCR RB1 The present study analyses the regulatory activity of a Human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. 33060578 chr13 27917232 27919232 PDX1 NFaT transcription factors, rather than the cano_x005f_x0002_nical PDX1 enhancer complex, are predicted to drive INS transactivation. human High+Lowthroughput Aberrant methylation underlies insulin gene expression in Human insulinoma 不相关 insulinoma Beta cell E_01_0966 PCR NFaT transcription factors, rather than the cano_x005f_x0002_nical PDX1 enhancer complex, are predicted to drive INS transactivation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NFaT transcription factors, rather than the cano_x005f_x0002_nical PDX1 enhancer complex, are predicted to drive INS transactivation. Immunohistochemical staining NFaT transcription factors, rather than the cano_x005f_x0002_nical PDX1 enhancer complex, are predicted to drive INS transactivation. PCR PDX1 NFaT transcription factors, rather than the cano_x005f_x0002_nical PDX1 enhancer complex, are predicted to drive INS transactivation. 33057201 chr4 105142814 105144814 TET2 In silico-informed in vitro evaluation of the TET2 germline locus enabled the identifcation of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. human High+Lowthroughput Inherited causes of clonal haematopoiesis in 97,691 whole genomes 相关 rs13167280,rs1210060191 hematopoietic stem cell E_01_0967 PCR,RNA-seq In silico-informed in vitro evaluation of the TET2 germline locus enabled the identifcation of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In silico-informed in vitro evaluation of the TET2 germline locus enabled the identifcation of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Immunohistochemical staining In silico-informed in vitro evaluation of the TET2 germline locus enabled the identifcation of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. PCR,RNA-seq TET2 In silico-informed in vitro evaluation of the TET2 germline locus enabled the identifcation of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. 33054858 chr16 67870026 67872026 EDC4 Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. human High+Lowthroughput Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage 不相关 Cervical cancer cervical cancer cells E_01_0968 RT-PCR Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. Immunohistochemical staining Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. RT-PCR EDC4 Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. 33054540 chr20 52048868 52050868 ZFP64 Expressions of notch intracellular domain (NICD) and hairy and enhancer of split 1 (Hes-1) in H1975 cell were determined by western blot. Epithelial-mesenchymal transition (EMT)-related pro_x005f_x0002_teins (E-Cadherin and Vimentin) expressions were identified through qRT-PCR and western blot. human cancer High+Lowthroughput Function and mechanism exploration of zinc finger protein 64 in lung adenocarcinoma cell growth and metastasis 不相关 lung adenocarcinoma Lung adenocarcinoma cell E_01_0969 qRT-PCR,western blot Expressions of notch intracellular domain (NICD) and hairy and enhancer of split 1 (Hes-1) in H1975 cell were determined by western blot. Epithelial-mesenchymal transition (EMT)-related pro_x005f_x0002_teins (E-Cadherin and Vimentin) expressions were identified through qRT-PCR and western blot. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expressions of notch intracellular domain (NICD) and hairy and enhancer of split 1 (Hes-1) in H1975 cell were determined by western blot. Epithelial-mesenchymal transition (EMT)-related pro_x005f_x0002_teins (E-Cadherin and Vimentin) expressions were identified through qRT-PCR and western blot. Immunohistochemical staining Expressions of notch intracellular domain (NICD) and hairy and enhancer of split 1 (Hes-1) in H1975 cell were determined by western blot. Epithelial-mesenchymal transition (EMT)-related pro_x005f_x0002_teins (E-Cadherin and Vimentin) expressions were identified through qRT-PCR and western blot. qRT-PCR,western blot ZFP64 Expressions of notch intracellular domain (NICD) and hairy and enhancer of split 1 (Hes-1) in H1975 cell were determined by western blot. Epithelial-mesenchymal transition (EMT)-related pro_x005f_x0002_teins (E-Cadherin and Vimentin) expressions were identified through qRT-PCR and western blot. 33054489 chr8 11674063 11676063 GATA4 Expressions of cell apoptotic proteins Bax, Cleaved(C) caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. human heart High+Lowthroughput MiR-33a-5p targets NOMO1 to modulate Human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis 不相关 congenital heart disease neural progenitor cell E_01_0970 qRT-PCR,Western blot Expressions of cell apoptotic proteins Bax, Cleaved(C) caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expressions of cell apoptotic proteins Bax, Cleaved(C) caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. Immunohistochemical staining Expressions of cell apoptotic proteins Bax, Cleaved(C) caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. qRT-PCR,Western blot GATA4 Expressions of cell apoptotic proteins Bax, Cleaved(C) caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. 33043448 chr22 42123656 42125656 CYP2D6 The rs5758550A>G SNP apparently turns the region into an enhancer that interacts with the CYP2D6 promoter and increases transcription. human High+Lowthroughput Tri-Allelic Haplotypes Determine and Differentiate Functionally Normal Allele CYP2D6*2 and Impaired Allele CYP2D6*41 相关 rs5758550 HCC cell E_01_0971 pcr,Western blotting The rs5758550A>G SNP apparently turns the region into an enhancer that interacts with the CYP2D6 promoter and increases transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The rs5758550A>G SNP apparently turns the region into an enhancer that interacts with the CYP2D6 promoter and increases transcription. Immunohistochemical staining The rs5758550A>G SNP apparently turns the region into an enhancer that interacts with the CYP2D6 promoter and increases transcription. pcr,Western blotting CYP2D6 The rs5758550A>G SNP apparently turns the region into an enhancer that interacts with the CYP2D6 promoter and increases transcription. 33035348 chr22 20077488 20079488 DGCR8 Here,we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. human High+Lowthroughput ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8 不相关 embryonic kidney 293E cell E_01_0972 PCR,Immunoprecipitation Here,we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here,we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Immunohistochemical staining Here,we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. PCR,Immunoprecipitation DGCR8 Here,we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. 32204915 chr16 67559503 67561503 CTCF TAD boundaries are enriched in binding of structural proteins (CTCF and cohesin)11. human blood High+Lowthroughput Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia 否 acute lymphoblastic leukemia E_01_0973 4C-seq，HiChIP，GRO-seq TAD boundaries are enriched in binding of structural proteins (CTCF and cohesin)11. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TAD boundaries are enriched in binding of structural proteins (CTCF and cohesin)11. Immunohistochemical staining TAD boundaries are enriched in binding of structural proteins (CTCF and cohesin)11. 4C-seq，HiChIP，GRO-seq CTCF TAD boundaries are enriched in binding of structural proteins (CTCF and cohesin)11. 32199616 chr19 15232997 15234997 BRD4 Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. human Human prostate cancer High+Lowthroughput Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer 否 prostatic cancer prostate cancer cell E_01_0974 Transfection, migration invasion assay, RT qPCR Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. Immunohistochemical staining Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. 转染，迁移侵袭测定，RT-qPCR BRD4 Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. 32194712 chr19 10651426 10653426 ILF3 Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. human High+Lowthroughput High expression of interleukin-enhancer binding factor 3 predicts poor prognosis in patients with lung adenocarcinoma 否 Lung adenocarcinoma E_01_0975 TMA, immunohistochemistry Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. Immunohistochemical staining Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. TMA,免疫组化 ILF3 Interleukin-enhancer binding factor 3 (ILF3) is a double-stranded RNA-binding protein that has been reported to contribute to the occurrence and progression of various malignant tumors. 32219447 chr3 128476870 128478870 GATA2 the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. human blood High+Lowthroughput Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia 是 Acute myeloid leukemia Leukemic blast cell E_01_0976 RNA sequencing, exon sequencing the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. Immunohistochemical staining the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. RNA测序，外显子测序 GATA2 the translocation of a GATA2 enhancer (3q21) to MECOM (3q26) results in overexpression of the MECOM isoform EVI1 and monoallelic expression of GATA2 from the unaffected allele. 32209656 chr21 34785474 34787474 RUNX1 involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto_x0002_oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), a human colorectal High+Lowthroughput Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells 否 Inflammatory diseases E_01_0977 RT qPCR, Western blot, ELISA involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto_x0002_oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), a Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto_x0002_oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), a Immunohistochemical staining involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto_x0002_oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), a RT-qPCR,western blot，酶联吸附反应 RUNX1 involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto_x0002_oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), a 32183903 chr5 37810291 37812291 GDNF GDNF is a dual promoter gene, and the promoter II with two enhancers and two silencers plays a major role in transcription initiation. human Glioblastoma High+Lowthroughput Crosstalk between DNA methylation and histone acetylation triggers GDNF high transcription in glioblastoma cells 否 Glioblastoma E_01_0978 RT-qPCR, Western blot, transfection, chip SEQ, chip PCR, re chip PCR, immunofluorescence GDNF is a dual promoter gene, and the promoter II with two enhancers and two silencers plays a major role in transcription initiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GDNF is a dual promoter gene, and the promoter II with two enhancers and two silencers plays a major role in transcription initiation. Immunohistochemical staining GDNF is a dual promoter gene, and the promoter II with two enhancers and two silencers plays a major role in transcription initiation. RT-QPCR，Western blot，转染，ChIP-seq、ChIP-PCR ， re-ChIP-PCR，免疫荧光 GDNF GDNF is a dual promoter gene, and the promoter II with two enhancers and two silencers plays a major role in transcription initiation. 32158256 chr9 117701191 117703191 TLR4 The pathway components were measured to evaluate the involvement of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) pathway. human cervical carcinoma High+Lowthroughput Procyanidin Compound (PC) Suppresses Lipopolysaccharide-Induced Cervical Cancer Cell Proliferation Through Blocking the TLR4/NF-κB Pathway 否 cervical carcinoma E_01_0979 CCK8, flow cytometry Western blot, RT-qPCR, scratch assay The pathway components were measured to evaluate the involvement of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The pathway components were measured to evaluate the involvement of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) pathway. Immunohistochemical staining The pathway components were measured to evaluate the involvement of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) pathway. CCK8，流式细胞术Western blot，RT-QPCR，划痕实验 TLR4 The pathway components were measured to evaluate the involvement of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) pathway. 32157157 chr13 20970532 20972532 LATS2 RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression human liver High+Lowthroughput Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation 否 Hepatic failure E_01_0980 Transfection, Western blot, chip SEQ, ELISA, TUNEL staining, he staining, immunohistochemistry RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression Immunohistochemical staining RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression 转染，Western blot，ChIP-seq，酶联免疫吸附，tunel染色，HE染色，免疫组化 LATS2 RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression 32153739 chr10 31315838 31317838 ZEB1 Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription fac_x0002_tor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). human gastric cancer High+Lowthroughput Investigation of the Correlation between Androgen Receptor and ZEB1 and its Value in Progression of Gastric Cancer 否 gastric cancer E_01_0981 Cytotoxicity assay, RT-qPCR, reverse transcription Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription fac_x0002_tor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription fac_x0002_tor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). Immunohistochemical staining Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription fac_x0002_tor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). 细胞毒性检测，RT-QPCR，逆转录 ZEB1 Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription fac_x0002_tor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). 32153563 chr18 79393019 79395019 NFATC1 We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain_x0002_enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). human lymph High+Lowthroughput Estrogen Receptor, Inflammatory, and FOXO Transcription Factors Regulate Expression of Myasthenia Gravis-Associated Circulating microRNAs 否 myasthenia gravis E_01_0982 ELISAs We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain_x0002_enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain_x0002_enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). Immunohistochemical staining We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain_x0002_enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). 酶联免疫吸附 NFATC1 We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain_x0002_enhancer of activated B cells (NF-κB), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). 32151175 chr8 47734528 47736528 CEBPD CCAAT enhancer-binding protein delta (CEBPD) is important in immune and inflammatory responses. human Thyroid cancer High+Lowthroughput MiR-324-5p/PTPRD/CEBPD axis promotes papillary thyroid carcinoma progression via microenvironment alteration 否 Thyroid cancer E_01_0983 RT-qPCR, transfection, CCK8, scratch assay, flow cytometry, Western blot CCAAT enhancer-binding protein delta (CEBPD) is important in immune and inflammatory responses. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CCAAT enhancer-binding protein delta (CEBPD) is important in immune and inflammatory responses. Immunohistochemical staining CCAAT enhancer-binding protein delta (CEBPD) is important in immune and inflammatory responses. RT-QPCR，转染，CCK8，划痕实验，流式细胞术，Western blot CEBPD CCAAT enhancer-binding protein delta (CEBPD) is important in immune and inflammatory responses. 32114505 chr13 49953816 49955816 DLEU2 We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), human liver cancer High+Lowthroughput Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription 否 Hepatocellular carcinoma E_01_0984 ChIP-seq，Western blot，RIP，ChIRP，ddPCR We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), Immunohistochemical staining We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), ChIP-seq，Western blot，RIP，ChIRP，ddPCR DLEU2 We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), 32113834 chr11 65495092 65497092 MALAT1 With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. human cervical carcinoma High+Lowthroughput IL-6/STAT3 mediates the HPV18 E6/E7 stimulated upregulation of MALAT1 gene in cervical cancer HeLa cells 否 cervical carcinoma E_01_0985 RNA isolation, RT-qPCR, Western blot, luciferase reporter assay With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. Immunohistochemical staining With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. RNA分离，RT-QPCR，Western blot，荧光素酶报告测定 MALAT1 With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. 32103293 chr17 42310440 42312440 STAT3 Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. human tumour High+Lowthroughput Myeloid‑derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma 否 OSCC E_01_0986 Flow cytometry, Western blot, RT-qPCR, ELISA Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. Immunohistochemical staining Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. 流式细胞术，Western blot，RT-QPCR，Elisa STAT3 Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. 32098781 chr11 1980587 1982587 MRPL23-AS1 MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of SACC patients, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an 'exosomecrine' manner. human oral cavity High+Lowthroughput Long Noncoding RNA MRPL23-AS1 Promotes Adenoid Cystic Carcinoma Lung Metastasis 否 Initiating cystic carcinoma lung metastases E_01_0987 RT-qPCR, invasion migration assay of transfected cells, Western blot, rip SEQ, chip SEQ, rna-fish and immunofluorescence, flow cytometry MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of SACC patients, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an 'exosomecrine' manner. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of SACC patients, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an 'exosomecrine' manner. Immunohistochemical staining MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of SACC patients, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an 'exosomecrine' manner. RT-QPCR，转染细胞侵袭迁移检测，Western blot，RIP-seq，CHIP-seq，RNA-FISH和免疫荧光，流式细胞术 MRPL23-AS1 MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of SACC patients, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an 'exosomecrine' manner. 32095812 chr7 117284492 117286492 CFTR Within this TAD specific cis-regulatory elements (CREs) play critical roles in the reg_x0002_ulation of CFTR expression, either by acting as enhancers or as structural features that facilitate the recruitment of ac_x0002_tive elements to the gene promoter (6). human Lung adenocarcinoma High+Lowthroughput Looping of upstream cis-regulatory elements is required for CFTR expression in human airway epithelial cells 否 lung disease E_01_0988 RT qPCR, Erna detection, chip qPCR, chip SEQ, luciferase detection, Within this TAD specific cis-regulatory elements (CREs) play critical roles in the reg_x0002_ulation of CFTR expression, either by acting as enhancers or as structural features that facilitate the recruitment of ac_x0002_tive elements to the gene promoter (6). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Within this TAD specific cis-regulatory elements (CREs) play critical roles in the reg_x0002_ulation of CFTR expression, either by acting as enhancers or as structural features that facilitate the recruitment of ac_x0002_tive elements to the gene promoter (6). Immunohistochemical staining Within this TAD specific cis-regulatory elements (CREs) play critical roles in the reg_x0002_ulation of CFTR expression, either by acting as enhancers or as structural features that facilitate the recruitment of ac_x0002_tive elements to the gene promoter (6). RT-qPCR，eRNA检测，ChIP-qPCR，ChIP-seq，荧光素酶检测， CFTR Within this TAD specific cis-regulatory elements (CREs) play critical roles in the reg_x0002_ulation of CFTR expression, either by acting as enhancers or as structural features that facilitate the recruitment of ac_x0002_tive elements to the gene promoter (6). 32093567 chr3 52542758 52544758 PBRM1 The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, human Renal clear cell carcinoma High+Lowthroughput A novel EZH2 inhibitor induces synthetic lethality and apoptosis in PBRM1-deficient cancer cells 否 renal carcinoma E_01_0989 Transfection, Western blot, RNAi, flow cytometry The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, Immunohistochemical staining The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, 转染，Western blot，RNAi，流式细胞术 PBRM1 The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, 32093281 chr10 58382379 58384379 TFAM Besides, downregulation of PISD with siRNA reduced the level of LC3-II, indicating that depletion of TFAM retarded autophagy via inhibiting PISD expression. human tumour High+Lowthroughput Knockdown of TFAM in Tumor Cells Retarded Autophagic Flux through Regulating p53 Acetylation and PISD Expression 否 tumour E_01_0990 Transfection, Western blot, immunofluorescence, RT-qPCR, Besides, downregulation of PISD with siRNA reduced the level of LC3-II, indicating that depletion of TFAM retarded autophagy via inhibiting PISD expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Besides, downregulation of PISD with siRNA reduced the level of LC3-II, indicating that depletion of TFAM retarded autophagy via inhibiting PISD expression. Immunohistochemical staining Besides, downregulation of PISD with siRNA reduced the level of LC3-II, indicating that depletion of TFAM retarded autophagy via inhibiting PISD expression. 转染，Western blot，免疫荧光，RT-QPCR， TFAM Besides, downregulation of PISD with siRNA reduced the level of LC3-II, indicating that depletion of TFAM retarded autophagy via inhibiting PISD expression. 32067207 chr6 50815520 50817520 TFAP2B In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis. human Retinoblastoma High+Lowthroughput Long non-coding RNA TP73-AS1 promotes TFAP2B-mediated proliferation, metastasis and invasion in retinoblastoma via decoying of miRNA-874-3p 否 Retinoblastoma E_01_0991 RT-qPCR, MTT, transfection, flow cytometry, Western blot In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis. Immunohistochemical staining In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis. RT-QPCR，MTT，转染，流式细胞术，Western blot TFAP2B In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis. 32054946 chr3 60377473 60379473 Mbnl1 We previously reported that a nonsteroidal anti_x0002_infammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. mouse Myoblasts High+Lowthroughput Inhibition of cyclooxygenase-1 by nonsteroidal anti-infammatory drugs demethylates MeR2 enhancer and promotes Mbnl1 transcription in myogenic cells 否 Inflammatory diseases E_01_0992 Western blot, transfection, immunofluorescence, luciferase assay We previously reported that a nonsteroidal anti_x0002_infammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We previously reported that a nonsteroidal anti_x0002_infammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. Immunohistochemical staining We previously reported that a nonsteroidal anti_x0002_infammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. Western blot，转染，免疫荧光，荧光素酶检测 Mbnl1 We previously reported that a nonsteroidal anti_x0002_infammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. 32028069 chr2 105355146 105357146 FHL2 Increased FHL2 and androgen receptor (AR) expression and decreased CCAAT/enhancer-binding protein b (C/EBPb) expression were observed in hGCs from patients with PCOS. human granular cell High+Lowthroughput Up-regulated FHL2 inhibits ovulation through interacting with androgen receptor and ERK1/2 in polycystic ovary syndrome 否 PCOS E_01_0993 Immunofluorescence, transfection, RT-qPCR, Western blot, chip, Increased FHL2 and androgen receptor (AR) expression and decreased CCAAT/enhancer-binding protein b (C/EBPb) expression were observed in hGCs from patients with PCOS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Increased FHL2 and androgen receptor (AR) expression and decreased CCAAT/enhancer-binding protein b (C/EBPb) expression were observed in hGCs from patients with PCOS. Immunohistochemical staining Increased FHL2 and androgen receptor (AR) expression and decreased CCAAT/enhancer-binding protein b (C/EBPb) expression were observed in hGCs from patients with PCOS. 免疫荧光，转染，RT-QPCR，Western blot，CHIP， FHL2 Increased FHL2 and androgen receptor (AR) expression and decreased CCAAT/enhancer-binding protein b (C/EBPb) expression were observed in hGCs from patients with PCOS. 32021450 chr4 1868747 1870747 NSD2 Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase) human kidney High+Lowthroughput NSD2 Promotes Renal Cancer Progression Through Stimulating Akt/Erk Signaling 否 renal carcinoma E_01_0994 Immunofluorescence, immunohistochemistry, transfection. RT-qPCR, flow cytometry, Western blot Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase) Immunohistochemical staining Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase) 免疫荧光，免疫组化，转染。RT-QPCR，流式细胞术，Western blot NSD2 Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase) 32187157 chr22 42123841 42125841 CYP2D6 in a critical enhancer region downstream of the CYP2D6 promoter was proposed to modulate CYP2D6 activity, depending on its linkage disequilibrium (LD) with the common CYP2D6 SNP, rs16947. human High+Lowthroughput Distribution and linkage disequilibrium of the enhancer SNP rs5758550 among Latin American populations: influence of continental ancestry 是 rs5758550,rs16947,rs5030656,rs35742688 Ethnic origin effects E_01_0995 in a critical enhancer region downstream of the CYP2D6 promoter was proposed to modulate CYP2D6 activity, depending on its linkage disequilibrium (LD) with the common CYP2D6 SNP, rs16947. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq in a critical enhancer region downstream of the CYP2D6 promoter was proposed to modulate CYP2D6 activity, depending on its linkage disequilibrium (LD) with the common CYP2D6 SNP, rs16947. Immunohistochemical staining in a critical enhancer region downstream of the CYP2D6 promoter was proposed to modulate CYP2D6 activity, depending on its linkage disequilibrium (LD) with the common CYP2D6 SNP, rs16947. CYP2D6 in a critical enhancer region downstream of the CYP2D6 promoter was proposed to modulate CYP2D6 activity, depending on its linkage disequilibrium (LD) with the common CYP2D6 SNP, rs16947. 32186750 chr5 88714648 88716648 MEF2C EC cell lines transfected with vectors overexpressing miR‑638, its target gene myocyte enhancer factor 2C (MEF2C) or both, were constructed. human endometrium High+Lowthroughput Methylation‑associated silencing of miR‑638 promotes endometrial carcinoma progression by targeting MEF2C 否 Endometrial cancer E_01_0996 RT-qPCR, DNA methylation analysis, cell viability assay, Western blot EC cell lines transfected with vectors overexpressing miR‑638, its target gene myocyte enhancer factor 2C (MEF2C) or both, were constructed. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EC cell lines transfected with vectors overexpressing miR‑638, its target gene myocyte enhancer factor 2C (MEF2C) or both, were constructed. Immunohistochemical staining EC cell lines transfected with vectors overexpressing miR‑638, its target gene myocyte enhancer factor 2C (MEF2C) or both, were constructed. RT-QPCR，DNA甲基化分析，细胞活力检测，Western blot MEF2C EC cell lines transfected with vectors overexpressing miR‑638, its target gene myocyte enhancer factor 2C (MEF2C) or both, were constructed. 32017069 chr5 88714258 88716258 MEF2C The myocyte enhancer factor 2C gene (MEF2C), located at chromosome 5q14.3, encodes a transcription factor from the MCM1-agamous-deficiens_x0002_serum response factor family (Potthoff & Olson, 2007) human High+Lowthroughput High expression of myocyte enhancer factor 2C predicts poor prognosis for adult acute myeloid leukaemia with normal karyotype 否 Acute myeloid leukemia E_01_0997 RT-QPCR The myocyte enhancer factor 2C gene (MEF2C), located at chromosome 5q14.3, encodes a transcription factor from the MCM1-agamous-deficiens_x0002_serum response factor family (Potthoff & Olson, 2007) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The myocyte enhancer factor 2C gene (MEF2C), located at chromosome 5q14.3, encodes a transcription factor from the MCM1-agamous-deficiens_x0002_serum response factor family (Potthoff & Olson, 2007) Immunohistochemical staining The myocyte enhancer factor 2C gene (MEF2C), located at chromosome 5q14.3, encodes a transcription factor from the MCM1-agamous-deficiens_x0002_serum response factor family (Potthoff & Olson, 2007) RT-QPCR MEF2C The myocyte enhancer factor 2C gene (MEF2C), located at chromosome 5q14.3, encodes a transcription factor from the MCM1-agamous-deficiens_x0002_serum response factor family (Potthoff & Olson, 2007) 32012382 chr15 99562302 99564302 MEF2A TargetScan and MicroT-CDS predict myocyte enhancer factor-2A (MEF2A), a transcription factor that regulates peroxi_x0002_some proliferator-activated receptor-gamma coactivator (PGC1α) transcription human Peripheral blood High+Lowthroughput MiRNA-137-mediated modulation of mitochondrial dynamics regulates human neural stem cell fate 否 Neurological disorders E_01_0998 Transfection, RT-qPCR, Western blot, flow cytometry TargetScan and MicroT-CDS predict myocyte enhancer factor-2A (MEF2A), a transcription factor that regulates peroxi_x0002_some proliferator-activated receptor-gamma coactivator (PGC1α) transcription Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TargetScan and MicroT-CDS predict myocyte enhancer factor-2A (MEF2A), a transcription factor that regulates peroxi_x0002_some proliferator-activated receptor-gamma coactivator (PGC1α) transcription Immunohistochemical staining TargetScan and MicroT-CDS predict myocyte enhancer factor-2A (MEF2A), a transcription factor that regulates peroxi_x0002_some proliferator-activated receptor-gamma coactivator (PGC1α) transcription 转染，RT-QPCR，Western blot，流式细胞数 MEF2A TargetScan and MicroT-CDS predict myocyte enhancer factor-2A (MEF2A), a transcription factor that regulates peroxi_x0002_some proliferator-activated receptor-gamma coactivator (PGC1α) transcription 32009938 chr1 247412961 247414961 NLRP3 leucine rich repeat and pyrin domain containing 3 (NLRP3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the major neuroinflammatory pathways that intensify AD pathogenesis human Neuroblastoma High+Lowthroughput Inhibition of Amyloid-Beta Production, Associated Neuroinflammation, and Histone Deacetylase 2-Mediated Epigenetic Modifications Prevent Neuropathology in Alzheimer's Disease in vitro Model 否 Alzheimer disease E_01_0999 Congo red staining, Western blot leucine rich repeat and pyrin domain containing 3 (NLRP3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the major neuroinflammatory pathways that intensify AD pathogenesis Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq leucine rich repeat and pyrin domain containing 3 (NLRP3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the major neuroinflammatory pathways that intensify AD pathogenesis Immunohistochemical staining leucine rich repeat and pyrin domain containing 3 (NLRP3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the major neuroinflammatory pathways that intensify AD pathogenesis 刚果红染色，Western blot NLRP3 leucine rich repeat and pyrin domain containing 3 (NLRP3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the major neuroinflammatory pathways that intensify AD pathogenesis 32009798 chr7 148804280 148806280 EZH2 Emerging evidence reveals the vital role of enhancer of zeste homolog 2 (EZH2) in cancer chemoresistance. human breast High+Lowthroughput EZH2 Contributes To Cisplatin Resistance In Breast Cancer By Epigenetically Suppressing miR-381 Expression 否 mammary cancer E_01_1000 Transfection, RT-qPCR, Western blot, flow cytometry, chip, Emerging evidence reveals the vital role of enhancer of zeste homolog 2 (EZH2) in cancer chemoresistance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Emerging evidence reveals the vital role of enhancer of zeste homolog 2 (EZH2) in cancer chemoresistance. Immunohistochemical staining Emerging evidence reveals the vital role of enhancer of zeste homolog 2 (EZH2) in cancer chemoresistance. 转染，RT-QPCR，Western blot，流式细胞术，CHIP， EZH2 Emerging evidence reveals the vital role of enhancer of zeste homolog 2 (EZH2) in cancer chemoresistance. 32005028 chr7 148805071 148807071 EZH2 PSMA3-AS1 and miR-101 expression were explored using qRT-PCR in ESCC tissues and cell lines. Immunohistochemistry assays were carried out to analyze EZH2 (enhancer of zeste homolog) protein expression. human esophagus High+Lowthroughput Long non-coding RNA PSMA3-AS1 promotes malignant phenotypes of esophageal cancer by modulating the miR-101/EZH2 axis as a ceRNA 否 ESCC E_01_1001 RT qPCR, rip, luciferase reporter, Western blot, scratch assay, transfection PSMA3-AS1 and miR-101 expression were explored using qRT-PCR in ESCC tissues and cell lines. Immunohistochemistry assays were carried out to analyze EZH2 (enhancer of zeste homolog) protein expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PSMA3-AS1 and miR-101 expression were explored using qRT-PCR in ESCC tissues and cell lines. Immunohistochemistry assays were carried out to analyze EZH2 (enhancer of zeste homolog) protein expression. Immunohistochemical staining PSMA3-AS1 and miR-101 expression were explored using qRT-PCR in ESCC tissues and cell lines. Immunohistochemistry assays were carried out to analyze EZH2 (enhancer of zeste homolog) protein expression. RT-qPCR，RIP，荧光素酶报告，Western blot，划痕实验，转染 EZH2 PSMA3-AS1 and miR-101 expression were explored using qRT-PCR in ESCC tissues and cell lines. Immunohistochemistry assays were carried out to analyze EZH2 (enhancer of zeste homolog) protein expression. 30945310 chr19 2508640 2510640 GNG7 Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment. human High+Lowthroughput G Protein γ subunit 7 loss contributes to progression of clear cell renal cell carcinoma 否 clear cell renal cell carcinoma E_01_1002 Western blot, cell transfection Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment. Immunohistochemical staining Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment. Western blot、细胞转染技术 GNG7,GNG8 Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment.;Taken together, our findings suggest that GNG8 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment. 30944316 chr16 67559734 67561734 CTCF Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. human High+Lowthroughput Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance 否 hormone-induced breast cancer E_01_1003 ChIP-seq、3C-qPCR、RNA-seq、 Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. Immunohistochemical staining Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. ChIP-seq、3C-qPCR、RNA-seq、 CTCF Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. 30942441 chr2 136111440 136113440 CXCR4 Osteoarthritis (OA) is an aseptic inflammatory disease which is associated with the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. human lymphoid High+Lowthroughput miR‑146a‑5p expression is upregulated by the CXCR4 antagonist TN14003 and attenuates SDF‑1‑induced cartilage degradation 否 Osteoarthritis B cell E_01_1004 RT-qPCR、western blot Osteoarthritis (OA) is an aseptic inflammatory disease which is associated with the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Osteoarthritis (OA) is an aseptic inflammatory disease which is associated with the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. Immunohistochemical staining Osteoarthritis (OA) is an aseptic inflammatory disease which is associated with the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. RT-qPCR、western blot CXCR4 Osteoarthritis (OA) is an aseptic inflammatory disease which is associated with the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. 30942422 chr1 159915486 159917486 TAGLN2 Cervical cancer is a malignancy that threatens female health. The present study aimed to investigate the role of transgelin 2 (TAGLN2) in cervical cancer. human High+Lowthroughput Transgelin 2 overexpression inhibits cervical cancer cell invasion and migration 否 cervical cancer E_01_1005 Cell transfection techniques, RT qPCR, Western blot Cervical cancer is a malignancy that threatens female health. The present study aimed to investigate the role of transgelin 2 (TAGLN2) in cervical cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Cervical cancer is a malignancy that threatens female health. The present study aimed to investigate the role of transgelin 2 (TAGLN2) in cervical cancer. Immunohistochemical staining Cervical cancer is a malignancy that threatens female health. The present study aimed to investigate the role of transgelin 2 (TAGLN2) in cervical cancer. 细胞转染技术、RT-qPCR、Western blot TAGLN2 Cervical cancer is a malignancy that threatens female health. The present study aimed to investigate the role of transgelin 2 (TAGLN2) in cervical cancer. 30942411 chr5 171384232 171386232 NPM1 A total of 11 frequent mutations were identified, including nucleophosmin 1 (NPM1), Fms related tyrosine kinase 3 (FLT3), DNA methyltransferase 3α (DNMT3A) and Notch 2 (NOTCH2), with a mutation rate of ≥10%. human High+Lowthroughput Mutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on next?generation sequencing 是 acute myeloid leukaemia E_01_1006 sequence A total of 11 frequent mutations were identified, including nucleophosmin 1 (NPM1), Fms related tyrosine kinase 3 (FLT3), DNA methyltransferase 3α (DNMT3A) and Notch 2 (NOTCH2), with a mutation rate of ≥10%. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A total of 11 frequent mutations were identified, including nucleophosmin 1 (NPM1), Fms related tyrosine kinase 3 (FLT3), DNA methyltransferase 3α (DNMT3A) and Notch 2 (NOTCH2), with a mutation rate of ≥10%. Immunohistochemical staining A total of 11 frequent mutations were identified, including nucleophosmin 1 (NPM1), Fms related tyrosine kinase 3 (FLT3), DNA methyltransferase 3α (DNMT3A) and Notch 2 (NOTCH2), with a mutation rate of ≥10%. 测序 NPM1 A total of 11 frequent mutations were identified, including nucleophosmin 1 (NPM1), Fms related tyrosine kinase 3 (FLT3), DNA methyltransferase 3α (DNMT3A) and Notch 2 (NOTCH2), with a mutation rate of ≥10%. 30941855 chr18 76976150 76978150 MBP Though there is one-amino-acid difference in the linker between maltose-binding protein (MBP) tag and DR3 DD, according to our self-interaction analysis, the hydrophobic interface discovered in MBP-hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. human High+Lowthroughput Crystal structure and activation mechanism of DR3 death domain 否 E_01_1007 Western blot, sequencing Though there is one-amino-acid difference in the linker between maltose-binding protein (MBP) tag and DR3 DD, according to our self-interaction analysis, the hydrophobic interface discovered in MBP-hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Though there is one-amino-acid difference in the linker between maltose-binding protein (MBP) tag and DR3 DD, according to our self-interaction analysis, the hydrophobic interface discovered in MBP-hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. Immunohistochemical staining Though there is one-amino-acid difference in the linker between maltose-binding protein (MBP) tag and DR3 DD, according to our self-interaction analysis, the hydrophobic interface discovered in MBP-hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. western blot、测序 MBP Though there is one-amino-acid difference in the linker between maltose-binding protein (MBP) tag and DR3 DD, according to our self-interaction analysis, the hydrophobic interface discovered in MBP-hDR3 DD crystal structure is responsible for both hDR3 DD and mDR3 DD homotypic interaction. 30940821 chr11 35135644 35137644 CD44 For example, the splicing factor class that consists of heterogeneous nuclear ribonucleoproteins (hnRNPs) is known to control metastasis formation by regulating alternative splicing of the small GTPase Rac17, but also by affecting CD44 isoform expression which increases TGFβ signaling8. human Tumor High+Lowthroughput Co-regulated gene expression of splicing factors as drivers of cancer progression 否 cancer tumor cell E_01_1008 Bioinformatic prediction For example, the splicing factor class that consists of heterogeneous nuclear ribonucleoproteins (hnRNPs) is known to control metastasis formation by regulating alternative splicing of the small GTPase Rac17, but also by affecting CD44 isoform expression which increases TGFβ signaling8. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For example, the splicing factor class that consists of heterogeneous nuclear ribonucleoproteins (hnRNPs) is known to control metastasis formation by regulating alternative splicing of the small GTPase Rac17, but also by affecting CD44 isoform expression which increases TGFβ signaling8. Immunohistochemical staining For example, the splicing factor class that consists of heterogeneous nuclear ribonucleoproteins (hnRNPs) is known to control metastasis formation by regulating alternative splicing of the small GTPase Rac17, but also by affecting CD44 isoform expression which increases TGFβ signaling8. 生物信息学预测 CD44 For example, the splicing factor class that consists of heterogeneous nuclear ribonucleoproteins (hnRNPs) is known to control metastasis formation by regulating alternative splicing of the small GTPase Rac17, but also by affecting CD44 isoform expression which increases TGFβ signaling8. 30940675 chr4 155042794 155044794 Hes5 DNA methylation array analysis identified hairy and enhancer of split 5 (Hes5) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. mouse High+Lowthroughput DNA methylation inhibitor attenuates polyglutamine-induced neurodegeneration by regulating Hes5 否 E_01_1009 Immunoblotting DNA methylation array analysis identified hairy and enhancer of split 5 (Hes5) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DNA methylation array analysis identified hairy and enhancer of split 5 (Hes5) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. Immunohistochemical staining DNA methylation array analysis identified hairy and enhancer of split 5 (Hes5) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. 免疫印迹 Hes5 DNA methylation array analysis identified hairy and enhancer of split 5 (Hes5) as having a CpG island with hyper-methylation in the promoter region, and the Hes5 expression was strongly silenced in SBMA. 30933372 chr20 44352856 44354856 HNF4A Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control the onset of hepatocyte cell fate. human High+Lowthroughput Hepatocyte Nuclear Factor 4-Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver 否 E_01_1010 co-IP Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control the onset of hepatocyte cell fate. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control the onset of hepatocyte cell fate. Immunohistochemical staining Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control the onset of hepatocyte cell fate. co-IP HNF1A Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control the onset of hepatocyte cell fate. 30930987 chr17 1776712 1778712 SMYD4 Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC. human Tumor High+Lowthroughput Expression patterns and the prognostic value of the SMYD family members in human breast carcinoma using integrative bioinformatics analysis 否 human breast carcinoma tumor cell E_01_1011 Bioinformatic prediction Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC. Immunohistochemical staining Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC. 生物信息学预测 SMYD4 Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC. 30926878 chr16 67559655 67561655 CTCF Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. human Tumor High+Lowthroughput The anti-cancer drugs curaxins target spatial genome organization 否 tumor cell E_01_1012 RT qPCR, immunoblot analysis Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. Immunohistochemical staining Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. RT-qPCR、免疫印迹分析 CTCF Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. 30923826 chr7 148804824 148806824 EZH2 Recently, we reported overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiting polycomb repressive complex 2 (PRC2), but the mechanism of action remained unclear. human High+Lowthroughput EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma 否 E_01_1013 Immunohistochemistry, Western blot Recently, we reported overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiting polycomb repressive complex 2 (PRC2), but the mechanism of action remained unclear. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Recently, we reported overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiting polycomb repressive complex 2 (PRC2), but the mechanism of action remained unclear. Immunohistochemical staining Recently, we reported overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiting polycomb repressive complex 2 (PRC2), but the mechanism of action remained unclear. 免疫组化、Western Blot EZH2 Recently, we reported overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiting polycomb repressive complex 2 (PRC2), but the mechanism of action remained unclear. 30922078 chr16 18801868 18803868 SMG1 Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. human epithelial cells High+Lowthroughput Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease 否 Heart Disease E_01_1014 Immunohistochemistry, gel electrophoresis, qPCR Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. Immunohistochemical staining Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. 免疫组化、凝胶电泳、 qPCR SMG1 Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. 29363553 chr6 47503992 47505992 Ezh2 Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. mouse Bone marrow High+Lowthroughput Hematopoietic stem/progenitor cell senescence is associated with altered expression profiles of cellular memory-involved gene 否 senescence associated disease progenitor cell E_02_0001 qRT-PCR Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. Immunohistochemical staining Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. qRT-PCR Ezh2 Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. 29358714 chr15 58585627 58587627 ADAM10 ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. human Nerve High+Lowthroughput Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks 否 Alzheimer’s disease SH-SY5Y human neuronal cell E_02_0002 Western blot,RT-PCR ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Immunohistochemical staining ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Western blot,RT-PCR ADAM10 ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. 29358650 chr4 139461205 139463205 Pax7 Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. mouse Hypophysoma High+Lowthroughput Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate 否 Hypophysoma AtT-20 cell E_02_0003 ChIP–seq,ATAC–seq,RNA-seq Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. Immunohistochemical staining Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. ChIP–seq,ATAC–seq,RNA-seq Pax7 Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. 29343853 chr7 78700257 78702257 Acan Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood mouse Cartilage High+Lowthroughput Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements 否 In debilitating diseases such as osteoarthritis, where increased mechanical stress on chondrocytes. chondroblast E_02_0004 Western blot Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood Immunohistochemical staining Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood Western blot Acan Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood 29343500 chr9 123505056 123507056 Ccr9 Furthermore, cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, ccr9. mouse Thymus High+Lowthroughput Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors 否 thymus homing thymocyte E_02_0005 Western blot,ChIP-seq,RNA-seq Furthermore, cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, ccr9. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, ccr9. Immunohistochemical staining Furthermore, cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, ccr9. Western blot,ChIP-seq,RNA-seq Ccr9,Cbfb Furthermore, cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, ccr9.;Cbfβ forms transcription factor complexes with runx proteins, and here we show that cbfβ2, encoded by an rnA splice variant of the cbfb gene, is essential for extrathymic differentiation of t cell progenitors. 29343483 chr7 34815932 34817932 Cebpa Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part through activation of a C/EBPα-driven anti-proliferative network by directly binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa transcription. mouse Bone marrow High+Lowthroughput NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of C/EBPα and inflammatory signaling 否 myelodysplastic disease hematopoietic stem cell E_02_0006 RT-qPCR Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part through activation of a C/EBPα-driven anti-proliferative network by directly binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part through activation of a C/EBPα-driven anti-proliferative network by directly binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa transcription. Immunohistochemical staining Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part through activation of a C/EBPα-driven anti-proliferative network by directly binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa transcription. RT-qPCR Cebpa Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part through activation of a C/EBPα-driven anti-proliferative network by directly binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa transcription. 29343442 chr12 57092345 57094345 STAT6 Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli. human Bone marrow High+Lowthroughput The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages 否 inflammatory diseases macrophage E_02_0007 ATAC-seq, ChIP-seq,GRO-seq,RNA-seq,Western Blot,qPCR,ChIP-qPCR Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli. Immunohistochemical staining Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli. ATAC-seq, ChIP-seq,GRO-seq,RNA-seq,Western Blot,qPCR,ChIP-qPCR STAT6,HDAC3 Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli.;The Presence of HDAC3 Is Required for IL-4-STAT6-Mediated Repression on a Subset of Genes 29342133 chr15 63714919 63952099 Myc The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies mouse Haematopoietic Low+High throughput A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies 否 Leukaemia hematopoietic stem cell E_02_0008 ChIP-seq Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a ‘super_x0002_enhancer’2 is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors. Super-Enhancer -- ChIP-seq,ATAC-seq,RT-qPCR AU0167572,Niard,Nird,bHLHe39,?Myc Clusters of enhancers, such as BENC, form highly combinatorial systems that allow precise control of gene expression across normal cellular hierarchies and which also can be hijacked in malignancies. ATAC-seq,RT-qPCR Analysis of mice carrying deletions of individual Enhancer modules suggests that specific Myc expression levels throughout most of the haematopoietic hierarchy are controlled by the combinatorial and additive activity of individual Enhancer modules, which collectively function as a ‘blood Enhancer cluster’(BENC). -- -- -- -- Myc -- In line with this hypothesis, chromatin conformation capture performedon mouse leukaemic cells2 as well as DNA proximity analysis using fluorescence in situ hybridization (DNA FISH) in LSK cells showed that the Myc promoter and BENC are in close physical proximity to each other, suggesting that cis-regulation is mediated by chromosomal looping in haematopoietic stem and progenitor cells. -- 29331299 chr16 29880720 29882720 Hes1 During the transition from osteoblasts to osteocytes, Hes1 is upregulated rather than Hes3 and Hes5, and Hes3 and Hes5 null mice display no skeletal phenotype, indicating that Hes1 is a major target of Notch signaling conduction in the skeleton mouse Bone High+Lowthroughput The regulatory roles of Notch in osteocyte differentiation via the crosstalk with canonical Wnt pathways during the transition of osteoblasts to osteocytes 否 osteocyte E_02_0009 RT-qPCR,Western blot, transfection, Immunofluorescence During the transition from osteoblasts to osteocytes, Hes1 is upregulated rather than Hes3 and Hes5, and Hes3 and Hes5 null mice display no skeletal phenotype, indicating that Hes1 is a major target of Notch signaling conduction in the skeleton Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq During the transition from osteoblasts to osteocytes, Hes1 is upregulated rather than Hes3 and Hes5, and Hes3 and Hes5 null mice display no skeletal phenotype, indicating that Hes1 is a major target of Notch signaling conduction in the skeleton Immunohistochemical staining During the transition from osteoblasts to osteocytes, Hes1 is upregulated rather than Hes3 and Hes5, and Hes3 and Hes5 null mice display no skeletal phenotype, indicating that Hes1 is a major target of Notch signaling conduction in the skeleton RT-qPCR,Western blot, transfection, Immunofluorescence Hes1 During the transition from osteoblasts to osteocytes, Hes1 is upregulated rather than Hes3 and Hes5, and Hes3 and Hes5 null mice display no skeletal phenotype, indicating that Hes1 is a major target of Notch signaling conduction in the skeleton 29321660 chr3 186043535 186045535 ETV5 Altogether, these results define the ERK–ETV5–RET pathway as a critical axis driving neuroblastoma oncogenesis downstream of activated ALK. human Neuroblastoma High+Lowthroughput Activated ALK signals through the ERK-ETV5-RET pathway to drive neuroblastoma oncogenesis 否 neuroblastoma neuroblastoma cell lines E_02_0010 ChIP-seq,RT-qPCR Altogether, these results define the ERK–ETV5–RET pathway as a critical axis driving neuroblastoma oncogenesis downstream of activated ALK. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Altogether, these results define the ERK–ETV5–RET pathway as a critical axis driving neuroblastoma oncogenesis downstream of activated ALK. Immunohistochemical staining Altogether, these results define the ERK–ETV5–RET pathway as a critical axis driving neuroblastoma oncogenesis downstream of activated ALK. ChIP-seq,RT-qPCR ETV5,RET Altogether, these results define the ERK–ETV5–RET pathway as a critical axis driving neuroblastoma oncogenesis downstream of activated ALK.;Altogether, these results define the ERK–ETV5–RET pathway as a critical axis driving neuroblastoma oncogenesis downstream of activated ALK. 29321583 chr3 34155732 34157732 Sox2ot Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development. mouse Embryo High+Lowthroughput Allele-specific repression of Sox2 through the long non-coding RNA Sox2ot 否 embryonic stem cell E_02_0011 qRT-PCR,qPCR,ChIP,3C Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development. Immunohistochemical staining Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development. qRT-PCR,qPCR,ChIP,3C Sox2ot,Sox2 Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development.;The transcription factor Sox2 controls the fate of pluripotent stem cells and neural stem cells. 29320736 chr15 41514637 41516637 RPAP1 We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity. human Connective High+Lowthroughput The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity 否 maintaining cell identity stem cell E_02_0012 ChIP-qPCR,ChIP-Seq,RNA-Seq,qRT-PCR We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity. Immunohistochemical staining We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity. ChIP-qPCR,ChIP-Seq,RNA-Seq,qRT-PCR RPAP1 We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity. 29320702 chr1 3066690 3068690 PRDM16 These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis. human Adipose Tissue High+Lowthroughput Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis 否 obesity or type 2 diabetes fat cell E_02_0013 RNA-Seq,ChIP These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis. Immunohistochemical staining These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis. RNA-Seq,ChIP PRDM16,GTF2IRD1,EHMT1 These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.;These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.;These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis. 29302059 chr1 133246792 133248792 Kiss1 Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. mouse Hypothalamic High+Lowthroughput Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty 否 female puberty Automatic Recognition of Cells E_02_0014 qPCR,RNA-seq,ChIP Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Immunohistochemical staining Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. qPCR,RNA-seq,ChIP Kiss1 Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. 29301908 chr6 6874986 6876986 Dlx5 Slc25a13hspn/hspn mice provide a new animal 40 model for studying long-range enhancer effects on Dlx5 expression in the developing inner ear. mouse Inner ear High+Lowthroughput Deletion of a Long-Range Dlx5 Enhancer Disrupts Inner Ear Development in Mice 否 inner ear dysmorphologies inner hair cells E_02_0015 DNA-seq Slc25a13hspn/hspn mice provide a new animal 40 model for studying long-range enhancer effects on Dlx5 expression in the developing inner ear. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Slc25a13hspn/hspn mice provide a new animal 40 model for studying long-range enhancer effects on Dlx5 expression in the developing inner ear. Immunohistochemical staining Slc25a13hspn/hspn mice provide a new animal 40 model for studying long-range enhancer effects on Dlx5 expression in the developing inner ear. DNA-seq Dlx5,Slc25a13 Slc25a13hspn/hspn mice provide a new animal 40 model for studying long-range enhancer effects on Dlx5 expression in the developing inner ear.;Slc25a13hspn/hspn mice provide a new animal 40 model for studying long-range enhancer effects on Dlx5 expression in the developing inner ear. 29297498 chr16 29880412 29882412 Hes1 Thus, our results support that IEC-intrinsic Hes1 maintains gut homeostasis by preventing microbial dysbiosis partially through regulating mucosal microhabitats. mouse Small intestine High+Lowthroughput Epithelial Hes1 maintains gut homeostasis by preventing microbial dysbiosis 否 intestinal microbial dysbiosis and disturbed homeostasis enterocyte E_02_0016 qPCR,Western blot Thus, our results support that IEC-intrinsic Hes1 maintains gut homeostasis by preventing microbial dysbiosis partially through regulating mucosal microhabitats. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, our results support that IEC-intrinsic Hes1 maintains gut homeostasis by preventing microbial dysbiosis partially through regulating mucosal microhabitats. Immunohistochemical staining Thus, our results support that IEC-intrinsic Hes1 maintains gut homeostasis by preventing microbial dysbiosis partially through regulating mucosal microhabitats. qPCR,Western blot Hes1 Thus, our results support that IEC-intrinsic Hes1 maintains gut homeostasis by preventing microbial dysbiosis partially through regulating mucosal microhabitats. 29257325 chr5 88714072 88716072 MEF2C The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T-box transcription factor 5, and heartand neural crest derivatives-expressed protein 2 (GMTH) human Heart High+Lowthroughput Optimization and enrichment of induced cardiomyocytes derived from mouse fibroblasts by reprogramming with cardiac transcription factors 否 Ischemic heart disease cardiac muscle cell (sensu Arthopoda) E_02_0017 RT-qPCR,qPCR,Immunostaining The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T-box transcription factor 5, and heartand neural crest derivatives-expressed protein 2 (GMTH) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T-box transcription factor 5, and heartand neural crest derivatives-expressed protein 2 (GMTH) Immunohistochemical staining The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T-box transcription factor 5, and heartand neural crest derivatives-expressed protein 2 (GMTH) RT-qPCR,qPCR,Immunostaining MEF2C The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T-box transcription factor 5, and heartand neural crest derivatives-expressed protein 2 (GMTH) 29256171 chr10 24357349 24375452 CCN2 CCN2 is a critical matricellular protein that is expressed in several cells with major implications in physiology and different pathologies. human Connective Low+High throughput Multiple enhancer regions govern the transcription of CCN2 during embryonic development 否 -- endothelial cell E_02_0018 Transgenic mice,ChIP-seq,DNase I Hypersensitivity Assay Four functional enhancers were identified, with each driving distinct, tissue-specific patterns of transgene expression. An enhancer located -100 kb from the CCN2 transcription start site facilitated expression within vascular tissue. An enhancer -135 kb upstream of CCN2 drove expression within the articular chondrocytes of synovial joints.The other two enhancers, located at -198 kb and -229 kb, mediated transgene expression within dermal fibroblasts, however the most prevalent activity was found within hypertrophic chondrocytes and periosteal tissue, respectively. Enhancer -- PCR,Transgenic mice Ctgf,Fisp12,Hcs24,fisp-12 -- -- -- -- -- -- -- Ccn2 -- Four functional enhancers were identified, with each driving distinct, tissue-specific patterns of transgene expression. An enhancer located -100 kb from the CCN2 transcription start site facilitated expression within vascular tissue. An enhancer -135 kb upstream of CCN2 drove expression within the articular chondrocytes of synovial joints.The other two enhancers, located at -198 kb and -229 kb, mediated transgene expression within dermal fibroblasts, however the most prevalent activity was found within hypertrophic chondrocytes and periosteal tissue, respectively. -- 29255029 chr5 28659278 28661278 Shh Transcriptome analysis indicates that ectopic expression of Shh up-regulates Chordin (Chrd) that antagonizes bone morphogenetic protein signaling in the interdigital region. mouse Toe High+Lowthroughput Enhancer adoption caused by genomic insertion elicits interdigital Shh expression and syndactyly in mouse 否 syndactyly interdigital cell E_02_0019 ATAC-seq,PCR Transcriptome analysis indicates that ectopic expression of Shh up-regulates Chordin (Chrd) that antagonizes bone morphogenetic protein signaling in the interdigital region. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcriptome analysis indicates that ectopic expression of Shh up-regulates Chordin (Chrd) that antagonizes bone morphogenetic protein signaling in the interdigital region. Immunohistochemical staining Transcriptome analysis indicates that ectopic expression of Shh up-regulates Chordin (Chrd) that antagonizes bone morphogenetic protein signaling in the interdigital region. ATAC-seq,PCR Shh Transcriptome analysis indicates that ectopic expression of Shh up-regulates Chordin (Chrd) that antagonizes bone morphogenetic protein signaling in the interdigital region. 29245050 chr13 83649881 83651881 Mef2c Interestingly, senescence and NANOG had dramatic effect on the expression level of Mef2c, which regulates myoblast proliferation by exercising transcriptional control of cell cycle related genes mouse Skeletal muscle High+Lowthroughput NANOG restores the impaired myogenic differentiation potential of skeletal myoblasts after multiple population doublings 否 impaired myogenic differentiation potential skeletal muscle myoblast E_02_0020 Western blot,Immunohistochemical Staining,qPCR Interestingly, senescence and NANOG had dramatic effect on the expression level of Mef2c, which regulates myoblast proliferation by exercising transcriptional control of cell cycle related genes Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interestingly, senescence and NANOG had dramatic effect on the expression level of Mef2c, which regulates myoblast proliferation by exercising transcriptional control of cell cycle related genes Immunohistochemical staining Interestingly, senescence and NANOG had dramatic effect on the expression level of Mef2c, which regulates myoblast proliferation by exercising transcriptional control of cell cycle related genes Western blot,Immunohistochemical Staining,qPCR Mef2c Interestingly, senescence and NANOG had dramatic effect on the expression level of Mef2c, which regulates myoblast proliferation by exercising transcriptional control of cell cycle related genes 29244146 chr7 148804295 148806295 EZH2 It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. human Embryonic High+Lowthroughput Ezh2 Mutations Found in the Weaver Overgrowth Syndrome Cause a Partial Loss of H3K27 Histone Methyltransferase Activity 否 Weaver syndrome chondroblast E_02_0021 Transfection,Immunostaining It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. Immunohistochemical staining It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. Transfection,Immunostaining EZH2 It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. 29223978 chr7 148804763 148806763 EZH2 Our results indicate that EZH2 is not required to repress chondrogenesis in the CM downstream of Wnt/b-catenin signaling. human Cartilage High+Lowthroughput PRC2 Is Dispensable in Vivo for β-Catenin-Mediated Repression of Chondrogenesis in the Mouse Embryonic Cranial Mesenchyme 否 chondroblast E_02_0022 Immunofluorescencet,RNA-seq ,RT–qPCR,ChIP-seq Our results indicate that EZH2 is not required to repress chondrogenesis in the CM downstream of Wnt/b-catenin signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results indicate that EZH2 is not required to repress chondrogenesis in the CM downstream of Wnt/b-catenin signaling. Immunohistochemical staining Our results indicate that EZH2 is not required to repress chondrogenesis in the CM downstream of Wnt/b-catenin signaling. Immunofluorescencet,RNA-seq ,RT–qPCR,ChIP-seq EZH2 Our results indicate that EZH2 is not required to repress chondrogenesis in the CM downstream of Wnt/b-catenin signaling. 29220426 chr13 116431913 116433913 Isl1 Insulin enhancer binding protein-1 (Isl1), a member of the LIM-homeodomain family, is a well-known activator of the insulin gene (14,15) and is essential for the development of the pancreas (16). mouse Liver High+Lowthroughput Isl1β Overexpression With Key β Cell Transcription Factors Enhances Glucose-Responsive Hepatic Insulin Production and Secretion 否 diabete b cell E_02_0023 Western blot,Luciferase Reporter Assay,qRT-PCR Insulin enhancer binding protein-1 (Isl1), a member of the LIM-homeodomain family, is a well-known activator of the insulin gene (14,15) and is essential for the development of the pancreas (16). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Insulin enhancer binding protein-1 (Isl1), a member of the LIM-homeodomain family, is a well-known activator of the insulin gene (14,15) and is essential for the development of the pancreas (16). Immunohistochemical staining Insulin enhancer binding protein-1 (Isl1), a member of the LIM-homeodomain family, is a well-known activator of the insulin gene (14,15) and is essential for the development of the pancreas (16). Western blot,Luciferase Reporter Assay,qRT-PCR Isl1 Insulin enhancer binding protein-1 (Isl1), a member of the LIM-homeodomain family, is a well-known activator of the insulin gene (14,15) and is essential for the development of the pancreas (16). 29207028 chr5 88714236 88716236 MEF2C Within the four key cellular signaling pathways involved in muscle fiber regulation, there are five important signaling factors: p38 MAPK, ERK2, CBP, MEF2C and AMPKα1. human Muscle High+Lowthroughput Role of the cofilin 2 gene in regulating the myosin heavy chain genes in mouse myoblast C2C12 cells 否 myofibrillar formation. C2C12 cells E_02_0024 RT-qPCR,RT-PCR,Western blot Within the four key cellular signaling pathways involved in muscle fiber regulation, there are five important signaling factors: p38 MAPK, ERK2, CBP, MEF2C and AMPKα1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Within the four key cellular signaling pathways involved in muscle fiber regulation, there are five important signaling factors: p38 MAPK, ERK2, CBP, MEF2C and AMPKα1. Immunohistochemical staining Within the four key cellular signaling pathways involved in muscle fiber regulation, there are five important signaling factors: p38 MAPK, ERK2, CBP, MEF2C and AMPKα1. RT-qPCR,RT-PCR,Western blot MEF2C Within the four key cellular signaling pathways involved in muscle fiber regulation, there are five important signaling factors: p38 MAPK, ERK2, CBP, MEF2C and AMPKα1. 29203251 chrX 67541434 67543434 AR Previous studies have shown that PCa development is closely-linked to the androgen receptor (AR) human Prostate High+Lowthroughput Androgen receptor (AR) degradation enhancer ASC-J9(?) in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth 否 prostate cancer prostate cancer cell E_02_0025 Western blot,qPCR Previous studies have shown that PCa development is closely-linked to the androgen receptor (AR) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Previous studies have shown that PCa development is closely-linked to the androgen receptor (AR) Immunohistochemical staining Previous studies have shown that PCa development is closely-linked to the androgen receptor (AR) Western blot,qPCR AR Previous studies have shown that PCa development is closely-linked to the androgen receptor (AR) 29180467 chr11 102107486 102109486 YAP1 In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. human Bladder High+Lowthroughput YAP1 and COX2 Coordinately Regulate Urothelial Cancer Stem-like Cells 否 urothelial carcinoma urothelial cell E_02_0026 Western blot,PCR In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Immunohistochemical staining In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Western blot,PCR YAP1,SOX2 In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition.;Here we report that the pro-inflammatory COX2/PGE2 pathway and the YAP1 growth regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSC. 29180399 chr19 15232268 15234268 BRD4 We therefore describe a novel oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL, and suggest targeting of these components as a potentially effective therapy for CTCL patients. human Skin High+Lowthroughput Diminished microRNA-29b level is associated with BRD4-mediated activation of oncogenes in cutaneous T-cell lymphoma 否 cutaneous T-cell lymphoma T cell E_02_0027 RT-PCR,ChIP,Transfection We therefore describe a novel oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL, and suggest targeting of these components as a potentially effective therapy for CTCL patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We therefore describe a novel oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL, and suggest targeting of these components as a potentially effective therapy for CTCL patients. Immunohistochemical staining We therefore describe a novel oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL, and suggest targeting of these components as a potentially effective therapy for CTCL patients. RT-PCR,ChIP,Transfection BRD4 We therefore describe a novel oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL, and suggest targeting of these components as a potentially effective therapy for CTCL patients. 29158184 chr11 112670256 112672256 Sox9 These findings link Sox9 to intrinsic mechanisms of TGF-β signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis mouse Kidney High+Lowthroughput TGF-β-mediated upregulation of Sox9 in fibroblast promotes renal fibrosis 否 renal fibrosis kidney fibroblast cell E_02_0028 Transfection,qPCR,ChIP These findings link Sox9 to intrinsic mechanisms of TGF-β signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings link Sox9 to intrinsic mechanisms of TGF-β signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis Immunohistochemical staining These findings link Sox9 to intrinsic mechanisms of TGF-β signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis Transfection,qPCR,ChIP Sox9 These findings link Sox9 to intrinsic mechanisms of TGF-β signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis 29155305 chr3 8725613 8727613 Hey1 Our data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation. These findings provide novel clues for the better understanding of tooth development mouse Tooth germ High+Lowthroughput Hey1 and Hey2 are differently expressed during mouse tooth development 否 tooth injury dental mesenchymal cell E_02_0029 qRT-PCR Our data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation. These findings provide novel clues for the better understanding of tooth development Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation. These findings provide novel clues for the better understanding of tooth development Immunohistochemical staining Our data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation. These findings provide novel clues for the better understanding of tooth development qRT-PCR Hey1,Hey2 Our data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation. These findings provide novel clues for the better understanding of tooth development;Our data implied that Hey2 function is restricted to transient amplifying cells of the ameloblast cell lineage and that Hey1 plays a role in the composition of the subodontoblastic layer, in addition to ameloblast differentiation. These findings provide novel clues for the better understanding of tooth development 29154784 chr16 29880401 29882401 Hes1 Sox9 and Hes1 are downstream targets of Jagged1–Notch signaling and are responsible for the timing of the maturation of primitive ductal structures mouse Liver High+Lowthroughput TGF-β1 signaling regulates mouse hepatic stellate cell differentiation via the Jagged1/Notch pathway 否 liver disease hepatic stellate cell E_02_0030 Western blot,ChIP,Transfection,qRT-PCR,Immunofluorescence Sox9 and Hes1 are downstream targets of Jagged1–Notch signaling and are responsible for the timing of the maturation of primitive ductal structures Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Sox9 and Hes1 are downstream targets of Jagged1–Notch signaling and are responsible for the timing of the maturation of primitive ductal structures Immunohistochemical staining Sox9 and Hes1 are downstream targets of Jagged1–Notch signaling and are responsible for the timing of the maturation of primitive ductal structures Western blot,ChIP,Transfection,qRT-PCR,Immunofluorescence Hes1 Sox9 and Hes1 are downstream targets of Jagged1–Notch signaling and are responsible for the timing of the maturation of primitive ductal structures 29148101 chr3 130901584 130903584 Lef1 Considering that Bmp2, Bmp4, and Lef1 are essential for promoting odontoblast differentiation, our findings are consistent with previous studies. mouse Tooth-germ High+Lowthroughput Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/β-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage 否 congenital tooth agenesis dental mesenchymal cell E_02_0031 Western blot,qPCR Considering that Bmp2, Bmp4, and Lef1 are essential for promoting odontoblast differentiation, our findings are consistent with previous studies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Considering that Bmp2, Bmp4, and Lef1 are essential for promoting odontoblast differentiation, our findings are consistent with previous studies. Immunohistochemical staining Considering that Bmp2, Bmp4, and Lef1 are essential for promoting odontoblast differentiation, our findings are consistent with previous studies. Western blot,qPCR Lef1 Considering that Bmp2, Bmp4, and Lef1 are essential for promoting odontoblast differentiation, our findings are consistent with previous studies. 29142074 chr7 94002773 94005073 STAT3 Yet, a certain threshold level of STAT3 activity is essential to support activation of the COL1A2 enhancer and TGFβ signalling in fibroblasts. human Lung Low throughput STAT3 controls COL1A2 enhancer activation cooperatively with JunB, regulates type I collagen synthesis posttranscriptionally, and is essential for lung myofibroblast differentiation 否 -- Myofibroblast E_02_0032 Luciferase Reporter Assay,ChIP The structure of the COL1A2 far-upstream enhancer and the HS4 region is shown in Figure 1A.Enhancer activation was determined by measuring luciferase expression. Enhancer -- Luciferase Reporter Assay,ChIP EDSARTH2,EDSCV,OI4 -- -- -- ADMIO,ADMIO1,APRF,HIES ChIP-qPCR -- -- COL1A2,COL1A2 STAT3,STAT3 We created two different luciferase reporter gene constructs under the control of the COL1A2 enhancer and proximal promoter.When the enhancer is engaged, it contacts the RNA polymerase complex forming at the collagen promoter. Thus, an RNA polymerase ChIP signal is a direct measure of enhancer engagement. ;We created two different luciferase reporter gene constructs under the control of the COL1A2 enhancer and proximal promoter.When the enhancer is engaged, it contacts the RNA polymerase complex forming at the collagen promoter. Thus, an RNA polymerase ChIP signal is a direct measure of enhancer engagement. ChIP analysis using qPCR for the binding of STAT3, JunB, and RNA polymerase II, in the HS4 region of SSc fibroblasts after treatment with SD1029, STAT3 siRNA (siSTAT3), or nontargeting siRNA (siNT). * = p < 0.05.;ChIP analysis using qPCR for the binding of STAT3, JunB, and RNA polymerase II, in the HS4 region of SSc fibroblasts after treatment with SD1029, STAT3 siRNA (siSTAT3), or nontargeting siRNA (siNT). * = p < 0.05. 29141987 chr2 103887795 103888195 Lmo2 T controls the expression of Lmo2, a master regulator of hematopoietic and endothelial development mouse Embryo Low+High throughput BRACHYURY directs histone acetylation to target loci during mesoderm development 否 -- hematopoietic and endothelial cell E_02_0033 ChIP-seq We overlapped TBS with genome‐wide H3K4me1 peaks from T WT mesodermal cells and found the same trend of decreased H3K27ac within ±1 kb of TBS/H3K4me1 sites (Fig EV4E), suggesting that T functions to coordinate H3K27ac at putative enhancer regions throughout the genome, and may regulate the switch between poised H3K4me1(+) enhancers and active H3K27ac/H3K4me1(+) enhancer regions. Enhancer -- RT-qPCR,ChIP-qPCR,ChIP-seq Rbtn-2,Rbtn2,Rhom-2,Ttg2 -- -- -- Bra,D17Mit170,Low,Lr1,Tbxt,Tl2,Tl3,cou,me75,T ChIP-seq,ChIP-qPCR -- -- Lmo2,Lmo2,Lmo2,Lmo2 T,T,T,T Both the ?70 enhancer and the TSS of Lmo2 display a decrease in H3K27ac in T Y88A mutant mesodermal cells, in the ChIP‐Seq data and confirmed by ChIP‐qPCR (Figs ?(Figs5A5A and B, and EV5A). We reasoned that T binding to the ?70 enhancer of Lmo2 may recruit permissive chromatin marks to the TSS to regulate expression, and that this regulation is disrupted in T Y88A mutant mesodermal cells.;Both the ?70 enhancer and the TSS of Lmo2 display a decrease in H3K27ac in T Y88A mutant mesodermal cells, in the ChIP‐Seq data and confirmed by ChIP‐qPCR (Figs ?(Figs5A5A and B, and EV5A). We reasoned that T binding to the ?70 enhancer of Lmo2 may recruit permissive chromatin marks to the TSS to regulate expression, and that this regulation is disrupted in T Y88A mutant mesodermal cells.;Both the ?70 enhancer and the TSS of Lmo2 display a decrease in H3K27ac in T Y88A mutant mesodermal cells, in the ChIP‐Seq data and confirmed by ChIP‐qPCR (Figs ?(Figs5A5A and B, and EV5A). We reasoned that T binding to the ?70 enhancer of Lmo2 may recruit permissive chromatin marks to the TSS to regulate expression, and that this regulation is disrupted in T Y88A mutant mesodermal cells.;Both the ?70 enhancer and the TSS of Lmo2 display a decrease in H3K27ac in T Y88A mutant mesodermal cells, in the ChIP‐Seq data and confirmed by ChIP‐qPCR (Figs ?(Figs5A5A and B, and EV5A). We reasoned that T binding to the ?70 enhancer of Lmo2 may recruit permissive chromatin marks to the TSS to regulate expression, and that this regulation is disrupted in T Y88A mutant mesodermal cells. We performed a co-immunoprecipitation analysis from in vitrodifferentiated mesodermal cells and found an interaction between endogenous T and p300.Strikingly, loss of H3K27ac was found at TBS upstream of the T genomic locus itself by ChIP-Seq . We validated this decrease in H3K27ac at the T genomic locus by ChIP-qPCR in TY88A and TWT mesodermal cells differentiated in vitro.;We performed a co-immunoprecipitation analysis from in vitrodifferentiated mesodermal cells and found an interaction between endogenous T and p300.Strikingly, loss of H3K27ac was found at TBS upstream of the T genomic locus itself by ChIP-Seq . We validated this decrease in H3K27ac at the T genomic locus by ChIP-qPCR in TY88A and TWT mesodermal cells differentiated in vitro.;We performed a co-immunoprecipitation analysis from in vitrodifferentiated mesodermal cells and found an interaction between endogenous T and p300.Strikingly, loss of H3K27ac was found at TBS upstream of the T genomic locus itself by ChIP-Seq . We validated this decrease in H3K27ac at the T genomic locus by ChIP-qPCR in TY88A and TWT mesodermal cells differentiated in vitro.;We performed a co-immunoprecipitation analysis from in vitrodifferentiated mesodermal cells and found an interaction between endogenous T and p300.Strikingly, loss of H3K27ac was found at TBS upstream of the T genomic locus itself by ChIP-Seq . We validated this decrease in H3K27ac at the T genomic locus by ChIP-qPCR in TY88A and TWT mesodermal cells differentiated in vitro. 29138985 chr4 108044731 108046731 LEF1 Lymphoid enhancer-binding factor-1 (LEF1) is one of the 48-kD nuclear proteins that is often expressed in the T and pre-B cells and is also a very significant member of the Wnt/β-catenin in embryonic stem cells human Skin High+Lowthroughput Effects of microRNA-708 on Epithelial-Mesenchymal Transition, Cell Proliferation and Apoptosis in Melanoma Cells by Targeting LEF1 through the Wnt Signaling Pathway 否 Melanoma Melanoma Cell Line E_02_0034 RT-qPCR,Dual-Luciferase Reporter Assay Lymphoid enhancer-binding factor-1 (LEF1) is one of the 48-kD nuclear proteins that is often expressed in the T and pre-B cells and is also a very significant member of the Wnt/β-catenin in embryonic stem cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lymphoid enhancer-binding factor-1 (LEF1) is one of the 48-kD nuclear proteins that is often expressed in the T and pre-B cells and is also a very significant member of the Wnt/β-catenin in embryonic stem cells Immunohistochemical staining Lymphoid enhancer-binding factor-1 (LEF1) is one of the 48-kD nuclear proteins that is often expressed in the T and pre-B cells and is also a very significant member of the Wnt/β-catenin in embryonic stem cells RT-qPCR,Dual-Luciferase Reporter Assay LEF1 Lymphoid enhancer-binding factor-1 (LEF1) is one of the 48-kD nuclear proteins that is often expressed in the T and pre-B cells and is also a very significant member of the Wnt/β-catenin in embryonic stem cells 29138798 chr3 8725482 8727482 Hey1 Taken together, the findings indicate that Hey1 may be a positive regulator of odontoblastic differentiation. mouse Dental pulp High+Lowthroughput Hey1 functions as a positive regulator of odontogenic differentiation in odontoblast?lineage cells 否 Oral Disease odontoblast E_02_0035 Western blot,ChIP,Transfection,RT‑qPCR,Immunofluorescence staining Taken together, the findings indicate that Hey1 may be a positive regulator of odontoblastic differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, the findings indicate that Hey1 may be a positive regulator of odontoblastic differentiation. Immunohistochemical staining Taken together, the findings indicate that Hey1 may be a positive regulator of odontoblastic differentiation. Western blot,ChIP,Transfection,RT‑qPCR,Immunofluorescence staining Hey1 Taken together, the findings indicate that Hey1 may be a positive regulator of odontoblastic differentiation. 29113912 chr14 18175266 18186392 Ang2 Importantly, sorafenib treatment, which suppresses H3K27 acetylation and Ang2 expression, profoundly halts the progression of Arid1a-deficient HCCs mouse Liver Low+High throughput Arid1a regulates response to anti-angiogenic therapy in advanced hepatocellular carcinoma 否 Hepatocellular Carcinoma HCC cell lines E_02_0036 ChIP-seq Notably, histone modification markers, including H3K4me1,H3K4me3, H3K27me3 and H3K27ac were presented at the Ang2 gene locus in liver tumor cells and were strongly colocal_x0002_ized with the two Arid1a-binding sites, suggesting an associa_x0002_tion between Arid1a binding and histone modification at the Ang2 gene locus (Fig. 4A). ChIP-qPCR analysis showed Arid1a knockdown increased the H3K27ac at the Ang2 proximal and distal regions. Enhancer -- ChIP-seq,ChIP-qPCR Angrp,Raa3,Rnase5b -- -- -- A430090G16,A730011L11,KAT3B,p300,p300 HAT ChIP-seq,ChIP-PCR -- -- Ang2,Ang2 Ep300,Ep300 Notably, histone modification markers, including H3K4me1,H3K4me3, H3K27me3 and H3K27ac were presented at the Ang2 gene locus in liver tumor cells and were strongly colocal_x0002_ized with the two Arid1a-binding sites, suggesting an associa_x0002_tion between Arid1a binding and histone modification at the Ang2 gene locus (Fig. 4A). ChIP-qPCR analysis showed Arid1a knockdown increased the H3K27ac at the Ang2 proximal and distal regions.;Notably, histone modification markers, including H3K4me1,H3K4me3, H3K27me3 and H3K27ac were presented at the Ang2 gene locus in liver tumor cells and were strongly colocal_x0002_ized with the two Arid1a-binding sites, suggesting an associa_x0002_tion between Arid1a binding and histone modification at the Ang2 gene locus (Fig. 4A). ChIP-qPCR analysis showed Arid1a knockdown increased the H3K27ac at the Ang2 proximal and distal regions. Interestingly,published ChIP-seq data also showed that p300 bound to the Ang2 gene locus, as we validated by ChIP-PCR.;Interestingly,published ChIP-seq data also showed that p300 bound to the Ang2 gene locus, as we validated by ChIP-PCR. 29107694 chr7 148804477 148806477 EZH2 Notably, EZH2 can catalyze histone H3 lysine 27 tri-methylation (H3K27me3) to inhibit gene transcription human Pancreas High+Lowthroughput Chaetospirolactone reverses the apoptotic resistance towards TRAIL in pancreatic cancer 否 pancreatic cancer pancreatic cancer cell E_02_0037 Western blot,ChIP,qPCR Notably, EZH2 can catalyze histone H3 lysine 27 tri-methylation (H3K27me3) to inhibit gene transcription Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Notably, EZH2 can catalyze histone H3 lysine 27 tri-methylation (H3K27me3) to inhibit gene transcription Immunohistochemical staining Notably, EZH2 can catalyze histone H3 lysine 27 tri-methylation (H3K27me3) to inhibit gene transcription Western blot,ChIP,qPCR EZH2 Notably, EZH2 can catalyze histone H3 lysine 27 tri-methylation (H3K27me3) to inhibit gene transcription 29059150 chr12 54572339 54574339 PPP1R1A We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element human Tumor High+Lowthroughput Protein phosphatase 1 regulatory subunit 1A in ewing sarcoma tumorigenesis and metastasis 否 ewing sarcoma ewing sarcoma cell E_02_0038 qRT–PCR,ChIP-Seq,Luciferase reporter assay We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element Immunohistochemical staining We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element qRT–PCR,ChIP-Seq,Luciferase reporter assay PPP1R1A We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element 29054992 chr5 69231968 69233968 CDK7 CDK7 is a key regulator of the cell cycle human Tumor High+Lowthroughput Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression 否 Tumor cancer cell E_02_0039 RNA-seq,ChIP-Seq,ChIP,RT-PCR CDK7 is a key regulator of the cell cycle Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CDK7 is a key regulator of the cell cycle Immunohistochemical staining CDK7 is a key regulator of the cell cycle RNA-seq,ChIP-Seq,ChIP,RT-PCR CDK7 CDK7 is a key regulator of the cell cycle 29024000 chr16 29880620 29882620 Hes1 In conclusion, we demonstrate that myeloid Notch1 deficiency promotes the JSAP1- mediated RhoA/ROCK signaling pathway and exacerbates liver damage by depressing its target gene Hes1 in IR-stressed livers. mouse Liver High+Lowthroughput Myeloid Notch1 deficiency activates the RhoA/ROCK pathway and aggravates hepatocellular damage in mouse ischemic livers 否 Liver Injury hepatocyte E_02_0040 Immunohistochemistry staining,qRT-PCR,Immunofluorescence staining In conclusion, we demonstrate that myeloid Notch1 deficiency promotes the JSAP1- mediated RhoA/ROCK signaling pathway and exacerbates liver damage by depressing its target gene Hes1 in IR-stressed livers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, we demonstrate that myeloid Notch1 deficiency promotes the JSAP1- mediated RhoA/ROCK signaling pathway and exacerbates liver damage by depressing its target gene Hes1 in IR-stressed livers. Immunohistochemical staining In conclusion, we demonstrate that myeloid Notch1 deficiency promotes the JSAP1- mediated RhoA/ROCK signaling pathway and exacerbates liver damage by depressing its target gene Hes1 in IR-stressed livers. Immunohistochemistry staining,qRT-PCR,Immunofluorescence staining Hes1 In conclusion, we demonstrate that myeloid Notch1 deficiency promotes the JSAP1- mediated RhoA/ROCK signaling pathway and exacerbates liver damage by depressing its target gene Hes1 in IR-stressed livers. 28970250 chr7 148804484 148806484 EZH2 Finally, EZH2 inhibition or PPARg activation ameliorated fibrogenesis in cKO mice. human Liver High+Lowthroughput SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice 否 liver fibrosis hepatic stellate cell E_02_0041 Western blot, qPCR,Transfection,ChIP Finally, EZH2 inhibition or PPARg activation ameliorated fibrogenesis in cKO mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Finally, EZH2 inhibition or PPARg activation ameliorated fibrogenesis in cKO mice. Immunohistochemical staining Finally, EZH2 inhibition or PPARg activation ameliorated fibrogenesis in cKO mice. Western blot, qPCR,Transfection,ChIP EZH2 Finally, EZH2 inhibition or PPARg activation ameliorated fibrogenesis in cKO mice. 28951561 chr17 42697786 42699786 EZH1 Taken together, these results show that dual inhibition of EZH1/2 is an effective strategy for eliminating AML LSCs. human Bone marrow High+Lowthroughput Dual inhibition of EZH1/2 breaks the quiescence of leukemia stem cells in acute myeloid leukemia 否 Acute myeloid leukemia leukemia stem cell E_02_0042 Western blot Taken together, these results show that dual inhibition of EZH1/2 is an effective strategy for eliminating AML LSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, these results show that dual inhibition of EZH1/2 is an effective strategy for eliminating AML LSCs. Immunohistochemical staining Taken together, these results show that dual inhibition of EZH1/2 is an effective strategy for eliminating AML LSCs. Western blot EZH1,EZH2 Taken together, these results show that dual inhibition of EZH1/2 is an effective strategy for eliminating AML LSCs.;Taken together, these results show that dual inhibition of EZH1/2 is an effective strategy for eliminating AML LSCs. 28898113 chr1 209782978 209784978 IRF6 Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. human Salivary gland High+Lowthroughput Interferon Regulatory Factor 6 Is Necessary for Salivary Glands and Pancreas Development 否 xerostomia acinar cell E_02_0043 Immunofluorescent Staining,RNA-Seq Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Immunohistochemical staining Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Immunofluorescent Staining,RNA-Seq IRF6 Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. 28752422 chr16 15702106 15704106 Cebpd These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts. mouse Bone High+Lowthroughput Regulation of Clock Genes by Adrenergic Receptor Signaling in Osteoblasts 否 cementoblast E_02_0044 These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts. Immunohistochemical staining These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts. Cebpd,Bmp4,Nfil3 These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts.;These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts.;These findings suggest that the effects of Cebpd are due to the circadian regulation of Bmp4 expression, at least in part, by the up-regulated expression of the clock gene Nfil3 in response to α1B-AR signaling in osteoblasts. 28744818 chr9 81580972 81582972 TLE1 Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice human Small intestine High+Lowthroughput Epigenetic modification of TLE1 induce abnormal differentiation in diabetic mice intestinal epithelium 否 diabetes mellitus enterocyte E_02_0045 Western Blot,RT-PCR,Dual-luciferase reporter assay Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice Immunohistochemical staining Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice Western Blot,RT-PCR,Dual-luciferase reporter assay TLE1,Hes1 Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice;Subsequently, TLE1, through the transcriptional suppression on expression of Hes1, contributes to the aberrant differentiation of IECs in DM mice 28720764 chr7 148804667 148806667 EZH2 The present results indicate that Abcg2 derepression induced by EZH2 mutations play crucial roles in MDS pathogenesis. human Bone marrow High+Lowthroughput High expression of ABCG2 induced by EZH2 disruption has pivotal roles in MDS pathogenesis 否 myelodysplastic syndromes bone marrow cell E_02_0046 SQ-RT-PCR,ChIP The present results indicate that Abcg2 derepression induced by EZH2 mutations play crucial roles in MDS pathogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present results indicate that Abcg2 derepression induced by EZH2 mutations play crucial roles in MDS pathogenesis. Immunohistochemical staining The present results indicate that Abcg2 derepression induced by EZH2 mutations play crucial roles in MDS pathogenesis. SQ-RT-PCR,ChIP EZH2,Abcg2 The present results indicate that Abcg2 derepression induced by EZH2 mutations play crucial roles in MDS pathogenesis.;The present results indicate that Abcg2 derepression induced by EZH2 mutations play crucial roles in MDS pathogenesis. 28621459 chr1 39078887 39080887 MACF1 Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes human Bone High+Lowthroughput Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting β-catenin/TCF1/Runx2 signaling axis 否 Osteoblast differentiation cementoblast E_02_0047 Western blot,Real time PCR Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes Immunohistochemical staining Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes Western blot,Real time PCR MACF1,LEF1 Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes;It has been demonstrated that TCF1 but not LEF1 binds directly to Runx2 promoter in MC3T3-E1 cells and that Runx2 is a direct target of β-catenin/TCF1 for the stimulation of osteoblast differentiation 28115742 chr5 88714348 88716348 MEF2C However, neurodevelopmental factors play an important role in schizophrenia,and alterations in MEF2C and other TF expression may have impacted diseased brains at earlier periods of pre- and postnatal life human Brain High+Lowthroughput MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice 否 schizophrenia and related disorders pluripotent stem cell E_02_0048 ChIP-seq,ChIP-PCR However, neurodevelopmental factors play an important role in schizophrenia,and alterations in MEF2C and other TF expression may have impacted diseased brains at earlier periods of pre- and postnatal life Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, neurodevelopmental factors play an important role in schizophrenia,and alterations in MEF2C and other TF expression may have impacted diseased brains at earlier periods of pre- and postnatal life Immunohistochemical staining However, neurodevelopmental factors play an important role in schizophrenia,and alterations in MEF2C and other TF expression may have impacted diseased brains at earlier periods of pre- and postnatal life ChIP-seq,ChIP-PCR MEF2C However, neurodevelopmental factors play an important role in schizophrenia,and alterations in MEF2C and other TF expression may have impacted diseased brains at earlier periods of pre- and postnatal life 26842780 chr22 39517640 39519640 ATF4 While suppressing general protein translation, eIF2α phosphorylation also promotes the selective translation of some mRNAs, such as ATF4 that induces CCAAT/enhancer binding homologous protein (CHOP), a pro-apoptotic transcription factor. human Spinal cord High+Lowthroughput Activating Transcription Factor-6α Deletion Modulates the Endoplasmic Reticulum Stress Response after Spinal Cord Injury but Does Not Affect Locomotor Recovery 否 Spinal cord injury Oligodendrocytes E_02_0049 Western blot,RT-PCR While suppressing general protein translation, eIF2α phosphorylation also promotes the selective translation of some mRNAs, such as ATF4 that induces CCAAT/enhancer binding homologous protein (CHOP), a pro-apoptotic transcription factor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq While suppressing general protein translation, eIF2α phosphorylation also promotes the selective translation of some mRNAs, such as ATF4 that induces CCAAT/enhancer binding homologous protein (CHOP), a pro-apoptotic transcription factor. Immunohistochemical staining While suppressing general protein translation, eIF2α phosphorylation also promotes the selective translation of some mRNAs, such as ATF4 that induces CCAAT/enhancer binding homologous protein (CHOP), a pro-apoptotic transcription factor. Western blot,RT-PCR ATF4 While suppressing general protein translation, eIF2α phosphorylation also promotes the selective translation of some mRNAs, such as ATF4 that induces CCAAT/enhancer binding homologous protein (CHOP), a pro-apoptotic transcription factor. 29028630 chr7 148804878 148806878 EZH2 EZH2 plays an important role in this inflammatory process of dental pulp. human dental pulp High+Lowthroughput EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors 否 dental pulp inflammation dental pulp cell E_02_0050 qPCR,ChIP,Western blot EZH2 plays an important role in this inflammatory process of dental pulp. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 plays an important role in this inflammatory process of dental pulp. Immunohistochemical staining EZH2 plays an important role in this inflammatory process of dental pulp. qPCR,ChIP,Western blot EZH2 EZH2 plays an important role in this inflammatory process of dental pulp. 31980609 chr1 47213215 47215215 TAL1 Allele-specific targeting of enCRISPRa to oncogenic TAL1 super-enhancer modulates TAL1 expression and cancer progression in xenotransplants. human lymph High+Lowthroughput Interrogation of enhancer function by enhancer_x0002_targeting CRISPR epigenetic editing 否 K562 cell，Jurkat cell E_02_0051 Flow cytometry, cell viability detection, QRT PCR, Western blot, RNA SEQ, chip SEQ, Allele-specific targeting of enCRISPRa to oncogenic TAL1 super-enhancer modulates TAL1 expression and cancer progression in xenotransplants. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Allele-specific targeting of enCRISPRa to oncogenic TAL1 super-enhancer modulates TAL1 expression and cancer progression in xenotransplants. Immunohistochemical staining Allele-specific targeting of enCRISPRa to oncogenic TAL1 super-enhancer modulates TAL1 expression and cancer progression in xenotransplants. 流式细胞术，细胞活力检测， qRT-PCR ，Western blot，RNA-seq，ChIP-seq， TAL1 Allele-specific targeting of enCRISPRa to oncogenic TAL1 super-enhancer modulates TAL1 expression and cancer progression in xenotransplants. 31980500 chr2 233757381 233759381 UGT1A1 An LXR specific enhancer site on the UGT1A1 gene was identified, along with convincing evidence that LXRα is crucial in maintaining constitutive expression of UGT1A1 in adult hUGT1 mice. human Liver, kidney High+Lowthroughput Differential role of LXRα and LXRβ in the regulation of UDP-glucuronosyltransferase 1A1 in humanized UGT1 mice 否 hepatic fibrosis HepG2，HK293 cell E_02_0052 QRT PCR, Western blot, glucuronidation assay, transfection, chromatin immunoprecipitation assay, agarose gel electrophoresis An LXR specific enhancer site on the UGT1A1 gene was identified, along with convincing evidence that LXRα is crucial in maintaining constitutive expression of UGT1A1 in adult hUGT1 mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq An LXR specific enhancer site on the UGT1A1 gene was identified, along with convincing evidence that LXRα is crucial in maintaining constitutive expression of UGT1A1 in adult hUGT1 mice. Immunohistochemical staining An LXR specific enhancer site on the UGT1A1 gene was identified, along with convincing evidence that LXRα is crucial in maintaining constitutive expression of UGT1A1 in adult hUGT1 mice. qRT-PCR，Western Blot，葡萄糖醛酸化分析，转染，染色质免疫沉淀分析，琼脂糖凝胶电泳 UGT1A1 An LXR specific enhancer site on the UGT1A1 gene was identified, along with convincing evidence that LXRα is crucial in maintaining constitutive expression of UGT1A1 in adult hUGT1 mice. 31968281 chr16 88712787 88714787 PIEZO1 Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD. human bone marrow High+Lowthroughput Identification of PIEZO1 polymorphisms for human bone mineral density 是 rs62048221 Osteoporotic fracture mesenchymal stem cell E_02_0053 Luciferase reporter assay, chip qPCR Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD. Immunohistochemical staining Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD. 荧光素酶报告分析，ChIP-qPCR PIEZO1 Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD. 31937792 chr9 78383023 78385023 Eef1a1 Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus. mouse embryo High+Lowthroughput Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus 否 tumour embryonic stem cell E_02_0054 Immunofluorescence, immunohistochemistry, he staining, Southern blot, PCR Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus. Immunohistochemical staining Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus. 免疫荧光，免疫组化，HE染色，Southern blot，PCR Eef1a1 Efficient tissue-type specific expression of target genes in a tetracycline-controlled manner from the ubiquitously active Eef1a1 locus. 31932307 chr20 21508188 21510188 NKX2-2 The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors human brain High+Lowthroughput The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors 否 CG4 cell E_02_0055 In situ hybridization, immunohistochemistry, immunofluorescence, CO immunoprecipitation, Western blot The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors Immunohistochemical staining The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors 原位杂交，免疫组化，免疫荧光，免疫共沉淀，Western blot NKX2-2 The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors 31927142 chr22 28791896 28793896 XBP1 Thus, XBP1 acts as an osmoprotective protein since it is activated by high osmolarity and upregulates lipid metabolism, membranes generation and the restoration of ER homeostasis. human kidney High+Lowthroughput X-box binding protein 1 (XBP1): A key protein for renal osmotic adaptation. Its role in lipogenic program regulation 否 MDCK cell E_02_0056 Transfection, RT-PCR, Western blot, immunofluorescence Thus, XBP1 acts as an osmoprotective protein since it is activated by high osmolarity and upregulates lipid metabolism, membranes generation and the restoration of ER homeostasis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Thus, XBP1 acts as an osmoprotective protein since it is activated by high osmolarity and upregulates lipid metabolism, membranes generation and the restoration of ER homeostasis. Immunohistochemical staining Thus, XBP1 acts as an osmoprotective protein since it is activated by high osmolarity and upregulates lipid metabolism, membranes generation and the restoration of ER homeostasis. 转染，RT-PCR，Western blot，免疫荧光 XBP1 Thus, XBP1 acts as an osmoprotective protein since it is activated by high osmolarity and upregulates lipid metabolism, membranes generation and the restoration of ER homeostasis. 31915257 chr11 27652693 27654693 BDNF CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons human brain High+Lowthroughput CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons 否 E_02_0057 RT qPCR, luciferase reporter assay, Western blot, immunocytochemistry, chromatin immunoprecipitation CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons Immunohistochemical staining CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons RT-qPCR ，荧光素酶报告试验，Western blot，免疫细胞化学，染色质免疫沉淀 BDNF CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons 31914694 chr7 148804420 148806420 EZH2 In conclusion, our results proved that EZH2 inhibition alleviated renal pyroptosis by blocking Nox4-dependent ROS generation through ALK5/Smad2/3 signaling pathway, indicating that EZH2 could be a potential therapeutic target for renal I/R injury. human kidney High+Lowthroughput Enhancer of zeste homolog 2 modulates oxidative stress-mediated pyroptosis in vitro and in a mouse kidney ischemia-reperfusion injury model 否 Renal ischemia reperfusion injury HK-2 cell E_02_0058 RT-PCR, Western blot, he staining, immunohistochemistry, TUNEL staining, cell viability assay, luciferase reporter assay, transfection, immunofluorescence In conclusion, our results proved that EZH2 inhibition alleviated renal pyroptosis by blocking Nox4-dependent ROS generation through ALK5/Smad2/3 signaling pathway, indicating that EZH2 could be a potential therapeutic target for renal I/R injury. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, our results proved that EZH2 inhibition alleviated renal pyroptosis by blocking Nox4-dependent ROS generation through ALK5/Smad2/3 signaling pathway, indicating that EZH2 could be a potential therapeutic target for renal I/R injury. Immunohistochemical staining In conclusion, our results proved that EZH2 inhibition alleviated renal pyroptosis by blocking Nox4-dependent ROS generation through ALK5/Smad2/3 signaling pathway, indicating that EZH2 could be a potential therapeutic target for renal I/R injury. RT-PCR，Western blot，HE染色，免疫组化，TUNEL染色，细胞活力检测，荧光素酶报告分析，转染，免疫荧光 EZH2 In conclusion, our results proved that EZH2 inhibition alleviated renal pyroptosis by blocking Nox4-dependent ROS generation through ALK5/Smad2/3 signaling pathway, indicating that EZH2 could be a potential therapeutic target for renal I/R injury. 31909872 chr5 177129035 177131035 NSD1 We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients. human High+Lowthroughput Investigating cortical features of Sotos syndrome using mice heterozygous for Nsd1. 否 Sotos syndrome E_02_0059 Immunofluorescence, genotyping PCR, qPCR, hematoxylin staining, We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients. Immunohistochemical staining We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients. 免疫荧光，基因分型PCR，qPCR，苏木精染色， NSD1 We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients. 31908011 chr2 199267108 199269108 SATB2 These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms. human Cord blood, skull High+Lowthroughput Maternal regulation of SATB2 in osteo-progeniters impairs skeletal development in offspring 否 Skeletal development mesenchymal stem cell，skull cells E_02_0060 Immunohistochemistry, chromatin immunoprecipitation, chip SEQ, RT qPCR, Western blot These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms. Immunohistochemical staining These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms. 免疫组化，染色质免疫沉淀，ChIP-seq，RT-qPCR，Western blot SATB2 These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms. 31865141 chr3 3142136 3144136 CRBN In conclusion, our study firstly provided a support that CRBN decrease effectively protected LPS-induced ALI against inflammatory response mainly through the repression of oxidative stress and ER stress. human lung High+Lowthroughput CRBN knockdown mitigates lipopolysaccharide-induced acute lung injury by suppression of oxidative stress and endoplasmic reticulum (ER) stress associated NF-κB signaling 否 acute lung injury A549 cell E_02_0061 Biochemical analysis, he staining, immunofluorescence, ELISA, Western blot, QRT PCR, intracellular reactive oxygen species detection In conclusion, our study firstly provided a support that CRBN decrease effectively protected LPS-induced ALI against inflammatory response mainly through the repression of oxidative stress and ER stress. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, our study firstly provided a support that CRBN decrease effectively protected LPS-induced ALI against inflammatory response mainly through the repression of oxidative stress and ER stress. Immunohistochemical staining In conclusion, our study firstly provided a support that CRBN decrease effectively protected LPS-induced ALI against inflammatory response mainly through the repression of oxidative stress and ER stress. 生化分析，HE染色，免疫荧光，ELISA，Western blot，qRT-PCR，细胞内活性氧检测 CRBN In conclusion, our study firstly provided a support that CRBN decrease effectively protected LPS-induced ALI against inflammatory response mainly through the repression of oxidative stress and ER stress. 31858612 chr14 53946742 53948742 BMP4 The expression levels of ALP, runt-related transcription factor 2, bone morphogenetic protein 4, osterix and β-catenin were significantly increased in GSK-137647A-treated group, while the gene and protein levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly reduced. human bone marrow High+Lowthroughput Effect of GSK-137647A, the first non-carboxylic FFA4 agonist, on the osteogenic and adipogenic differentiation of bone mesenchymal stem cells in db/db mice 否 mesenchymal stem cell of the bone marrow，cementoblast E_02_0062 Flow cytometry, cell viability assay, oil red O staining, Western blot, RT qPCR The expression levels of ALP, runt-related transcription factor 2, bone morphogenetic protein 4, osterix and β-catenin were significantly increased in GSK-137647A-treated group, while the gene and protein levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly reduced. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression levels of ALP, runt-related transcription factor 2, bone morphogenetic protein 4, osterix and β-catenin were significantly increased in GSK-137647A-treated group, while the gene and protein levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly reduced. Immunohistochemical staining The expression levels of ALP, runt-related transcription factor 2, bone morphogenetic protein 4, osterix and β-catenin were significantly increased in GSK-137647A-treated group, while the gene and protein levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly reduced. 流式细胞术，细胞活力检测，油红O染色，Western blot，RT-Qpcr BMP4 The expression levels of ALP, runt-related transcription factor 2, bone morphogenetic protein 4, osterix and β-catenin were significantly increased in GSK-137647A-treated group, while the gene and protein levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly reduced. 31845180 chr8 81475612 81477612 FABP4 Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes human High+Lowthroughput Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes 否 3T3-LL cell E_02_0063 Oil red O staining, Western blot Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes Immunohistochemical staining Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes 油红O染色，Western blot FABP4 Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes 31844321 chr5 129458078 129460078 ADAMTS19 Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance. human valve High+Lowthroughput Loss of ADAMTS19 causes progressive non-syndromic heart valve disease 否 Valvular heart disease valve interstitial cells E_02_0064 Immunohistochemistry, immunofluorescence, Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance. Immunohistochemical staining Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance. 免疫组化，免疫荧光， ADAMTS19 Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance. 31841397 chr7 148804351 148806351 EZH2 Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation human uterus High+Lowthroughput Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation 否 Uterine epithelial VAS epithelial cell of uterus E_02_0065 Immunohistochemistry, qPCR Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation Immunohistochemical staining Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation 免疫组化，qPCR EZH2 Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation 31840569 chr17 80542354 80544354 RPTOR Ultimately, atg7 rptor double-KO mice displayed decreased lipolysis, restored adipose tissue development, and upregulated thermogenic gene expression in brown and inguinal adipose tissue compared to RPTOR-deficient mice in vivo. human Fat High+Lowthroughput Sustained activation of autophagy suppresses adipocyte maturation via a lipolysis-dependent mechanism 否 fat cell E_02_0066 Immunofluorescence, flow cytometry, oil red O staining, he staining, immunohistochemistry, Western blot Ultimately, atg7 rptor double-KO mice displayed decreased lipolysis, restored adipose tissue development, and upregulated thermogenic gene expression in brown and inguinal adipose tissue compared to RPTOR-deficient mice in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ultimately, atg7 rptor double-KO mice displayed decreased lipolysis, restored adipose tissue development, and upregulated thermogenic gene expression in brown and inguinal adipose tissue compared to RPTOR-deficient mice in vivo. Immunohistochemical staining Ultimately, atg7 rptor double-KO mice displayed decreased lipolysis, restored adipose tissue development, and upregulated thermogenic gene expression in brown and inguinal adipose tissue compared to RPTOR-deficient mice in vivo. 免疫荧光，流式细胞术，油红O染色，HE染色，免疫组化，western blot RPTOR Ultimately, atg7 rptor double-KO mice displayed decreased lipolysis, restored adipose tissue development, and upregulated thermogenic gene expression in brown and inguinal adipose tissue compared to RPTOR-deficient mice in vivo. 31833556 chr7 148804595 148806595 EZH2 By conducting TF enrichment analyses, we identified EZH2 as a common TF binding to osteoporosis-associated enhancers, and EZH2 was also associated with BMD in a Chinese population. EZH2 is functionally related to bone phenotypes. human High+Lowthroughput Transcription Factor Enrichment Analysis in Enhancers Identifies EZH2 as a Susceptibility Gene for Osteoporosis 是 rs111851041 Osteoporosis E_02_0067 By conducting TF enrichment analyses, we identified EZH2 as a common TF binding to osteoporosis-associated enhancers, and EZH2 was also associated with BMD in a Chinese population. EZH2 is functionally related to bone phenotypes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By conducting TF enrichment analyses, we identified EZH2 as a common TF binding to osteoporosis-associated enhancers, and EZH2 was also associated with BMD in a Chinese population. EZH2 is functionally related to bone phenotypes. Immunohistochemical staining By conducting TF enrichment analyses, we identified EZH2 as a common TF binding to osteoporosis-associated enhancers, and EZH2 was also associated with BMD in a Chinese population. EZH2 is functionally related to bone phenotypes. EZH2 By conducting TF enrichment analyses, we identified EZH2 as a common TF binding to osteoporosis-associated enhancers, and EZH2 was also associated with BMD in a Chinese population. EZH2 is functionally related to bone phenotypes. 31815603 chr6 133886394 133888394 TCF21 These data indicate that TCF21 antagonizes the MYOCD-SRF pathway through multiple mechanisms, further establishing a role for this coronary artery disease-associated gene in fundamental SMC processes and indicating the importance of smooth muscle response to vascular stress and phenotypic modulation of this cell type in coronary artery disease risk. human coronary artery High+Lowthroughput Coronary Disease-Associated Gene TCF21 Inhibits Smooth Muscle Cell Differentiation by Blocking the Myocardin-Serum Response Factor Pathway 否 coronary artery disease smooth muscle cell E_02_0068 Western blot, chromatin immunoprecipitation sequencing, transfection These data indicate that TCF21 antagonizes the MYOCD-SRF pathway through multiple mechanisms, further establishing a role for this coronary artery disease-associated gene in fundamental SMC processes and indicating the importance of smooth muscle response to vascular stress and phenotypic modulation of this cell type in coronary artery disease risk. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These data indicate that TCF21 antagonizes the MYOCD-SRF pathway through multiple mechanisms, further establishing a role for this coronary artery disease-associated gene in fundamental SMC processes and indicating the importance of smooth muscle response to vascular stress and phenotypic modulation of this cell type in coronary artery disease risk. Immunohistochemical staining These data indicate that TCF21 antagonizes the MYOCD-SRF pathway through multiple mechanisms, further establishing a role for this coronary artery disease-associated gene in fundamental SMC processes and indicating the importance of smooth muscle response to vascular stress and phenotypic modulation of this cell type in coronary artery disease risk. Western Blot，染色质免疫沉淀测序，转染 TCF21 These data indicate that TCF21 antagonizes the MYOCD-SRF pathway through multiple mechanisms, further establishing a role for this coronary artery disease-associated gene in fundamental SMC processes and indicating the importance of smooth muscle response to vascular stress and phenotypic modulation of this cell type in coronary artery disease risk. 31786140 chr7 27195600 27197600 HOTTIP HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice human Kidney, bone marrow High+Lowthroughput HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice 否 Acute myeloid leukemia HEK293T cell，OCI-AML3 cell E_02_0069 QRT PCR, rip, flow cytometry, chromatin immunoprecipitation HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice Immunohistochemical staining HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice qRT-PCR，RIP，流式细胞术，染色质免疫沉淀 HOTTIP HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice 33081480 chr18 47806258 47808258 SMAD2 GLGZD was able to inhibit miR-155 upregulation, resulting in down-regulation of miR-155-targeted molecules in MCAO rats, including suppressor of cytokine signaling 1 (SOCS1), inhibitor of nuclear factor kappa-B kinase (IKK), mothers against decapentaplegic homolog 2 (SMAD2) and CCAAT/enhancer binding protein beta (CEBPβ). human brain High+Lowthroughput The inhibitory effect of Gualou Guizhi Decoction on post-ischemic neuroinflammation via miR-155 in MCAO rats 否 stroke Inflammatory cell E_02_0070 RT-qPCR，Western blot，Immunohistochemistry GLGZD was able to inhibit miR-155 upregulation, resulting in down-regulation of miR-155-targeted molecules in MCAO rats, including suppressor of cytokine signaling 1 (SOCS1), inhibitor of nuclear factor kappa-B kinase (IKK), mothers against decapentaplegic homolog 2 (SMAD2) and CCAAT/enhancer binding protein beta (CEBPβ). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GLGZD was able to inhibit miR-155 upregulation, resulting in down-regulation of miR-155-targeted molecules in MCAO rats, including suppressor of cytokine signaling 1 (SOCS1), inhibitor of nuclear factor kappa-B kinase (IKK), mothers against decapentaplegic homolog 2 (SMAD2) and CCAAT/enhancer binding protein beta (CEBPβ). Immunohistochemical staining GLGZD was able to inhibit miR-155 upregulation, resulting in down-regulation of miR-155-targeted molecules in MCAO rats, including suppressor of cytokine signaling 1 (SOCS1), inhibitor of nuclear factor kappa-B kinase (IKK), mothers against decapentaplegic homolog 2 (SMAD2) and CCAAT/enhancer binding protein beta (CEBPβ). RT-qPCR，Western blot，Immunohistochemistry SMAD2 GLGZD was able to inhibit miR-155 upregulation, resulting in down-regulation of miR-155-targeted molecules in MCAO rats, including suppressor of cytokine signaling 1 (SOCS1), inhibitor of nuclear factor kappa-B kinase (IKK), mothers against decapentaplegic homolog 2 (SMAD2) and CCAAT/enhancer binding protein beta (CEBPβ). 29861522 chr3 149159891 149161891 CP The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat. human Epithelial High+Lowthroughput Effect of diethyldithiocarbamate in cyclophosphamide-induced nephrotoxicity: Immunohistochemical study of superoxide dismutase 1 in rat 否 Renal impairment nephron tubule epithelial cell E_02_0071 Biochemical analyses,Immunohistochemistry The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat. Immunohistochemical staining The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat. Biochemical analyses,Immunohistochemistry CP,SOD1 The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat.;The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat. 29859467 chr10 67881752 67883752 SIRT1 Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects. human Epididymal white adipose High+Lowthroughput Qing Gan Zi Shen Tang alleviates adipose tissue dysfunction with up-regulation of SIRT1 in spontaneously hypertensive rat 否 Hypertension, obesity, hyperlipidemia, insulin resistance fat cell E_02_0072 ELISA,Western blot,Quantitative reverse transcription polymerase chain reaction (qRT-PCR),Immunohistochemistry analysis,HPLC Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects. Immunohistochemical staining Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects. ELISA,Western blot,Quantitative reverse transcription polymerase chain reaction (qRT-PCR),Immunohistochemistry analysis,HPLC SIRT1,FOXO1,FABP4 Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects.;Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects.;Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects. 31484726 chr12 53959112 53961112 HOTAIR Focusing on a well-known lncRNA, HOTAIR, four distinct epigenetic modification patterns were observed. The majority of HOTAIR binding sites (50.1%) were located within quiescent regions. human High+Lowthroughput Comprehensive analysis of long noncoding RNA (lncRNA)-chromatin interactions reveals lncRNA functions dependent on binding diverse regulatory elements 否 cervical carcinoma HeLa-S3 cell E_02_0073 PCR,Flow cytometry Focusing on a well-known lncRNA, HOTAIR, four distinct epigenetic modification patterns were observed. The majority of HOTAIR binding sites (50.1%) were located within quiescent regions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Focusing on a well-known lncRNA, HOTAIR, four distinct epigenetic modification patterns were observed. The majority of HOTAIR binding sites (50.1%) were located within quiescent regions. Immunohistochemical staining Focusing on a well-known lncRNA, HOTAIR, four distinct epigenetic modification patterns were observed. The majority of HOTAIR binding sites (50.1%) were located within quiescent regions. PCR,Flow cytometry HOTAIR Focusing on a well-known lncRNA, HOTAIR, four distinct epigenetic modification patterns were observed. The majority of HOTAIR binding sites (50.1%) were located within quiescent regions. 31484079 chr7 150942398 150944398 KCNH2 The human ether-a-go-go-related gene KCNH2 encodes the voltage-gated potassium channel underlying IKr, a current critical for the repolarization phase of the cardiac action potential. human liver High+Lowthroughput Identification and Characterization of a Transcribed Distal Enhancer Involved in Cardiac Kcnh2 Regulation 是 rs9640171 liver cancer hepatocellular carcinoma derived cell E_02_0074 PCR,Flow cytometry The human ether-a-go-go-related gene KCNH2 encodes the voltage-gated potassium channel underlying IKr, a current critical for the repolarization phase of the cardiac action potential. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The human ether-a-go-go-related gene KCNH2 encodes the voltage-gated potassium channel underlying IKr, a current critical for the repolarization phase of the cardiac action potential. Immunohistochemical staining The human ether-a-go-go-related gene KCNH2 encodes the voltage-gated potassium channel underlying IKr, a current critical for the repolarization phase of the cardiac action potential. PCR,Flow cytometry KCNH2 The human ether-a-go-go-related gene KCNH2 encodes the voltage-gated potassium channel underlying IKr, a current critical for the repolarization phase of the cardiac action potential. 29945972 chrX 49025737 49027737 TFE3 The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. human High+Lowthroughput Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress 否 cancer E_02_0075 Western blot, immunofluorescence staining The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. Immunohistochemical staining The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. western blot,免疫荧光染色 TFE3,IGHM The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways.;The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. 29945296 chr13 31737329 31739329 Foxq1 In particular, the Fox transcription factor binding motif was frequently observed within EWS FLI1 peaks and Foxq1 was identified as the cooperative partner that interacts with the EWS portion of EWS FLI1. mouse High+Lowthroughput EWS-FLI1 regulates a transcriptional program in cooperation with Foxq1 in mouse Ewing sarcoma 否 Ewing sarcoma E_02_0076 Real ‐ time quantitative PCR, luciferase assay, chip ‐ SEQ, statistical analysis In particular, the Fox transcription factor binding motif was frequently observed within EWS FLI1 peaks and Foxq1 was identified as the cooperative partner that interacts with the EWS portion of EWS FLI1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In particular, the Fox transcription factor binding motif was frequently observed within EWS FLI1 peaks and Foxq1 was identified as the cooperative partner that interacts with the EWS portion of EWS FLI1. Immunohistochemical staining In particular, the Fox transcription factor binding motif was frequently observed within EWS FLI1 peaks and Foxq1 was identified as the cooperative partner that interacts with the EWS portion of EWS FLI1. Real‐time quantitative PCR,Luciferase assay,ChIP‐Seq,统计分析 Foxq1 In particular, the Fox transcription factor binding motif was frequently observed within EWS FLI1 peaks and Foxq1 was identified as the cooperative partner that interacts with the EWS portion of EWS FLI1. 29941955 chr1 186441221 186443221 PDC Pyruvate decarboxylase (PDC), 1-amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS), glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal and seminal roots were more abundant in TF58 than those in TF57 under waterlogging stress. human High+Lowthroughput Elucidating the hypoxic stress response in barley (Hordeum vulgare L.) during waterlogging: A proteomics approach 否 E_02_0077 QRT PCR, Western blot, statistical analysis Pyruvate decarboxylase (PDC), 1-amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS), glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal and seminal roots were more abundant in TF58 than those in TF57 under waterlogging stress. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Pyruvate decarboxylase (PDC), 1-amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS), glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal and seminal roots were more abundant in TF58 than those in TF57 under waterlogging stress. Immunohistochemical staining Pyruvate decarboxylase (PDC), 1-amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS), glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal and seminal roots were more abundant in TF58 than those in TF57 under waterlogging stress. qRT-PCR,Western blot,统计分析 PDC Pyruvate decarboxylase (PDC), 1-amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS), glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal and seminal roots were more abundant in TF58 than those in TF57 under waterlogging stress. 29594316 chr1 26690341 26692341 ARID1A In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. human Lymphoid tissue, liver High+Lowthroughput ARID1A loss in adult hepatocytes activates β-catenin-mediated erythropoietin transcription 否 erythrocyte，stem cell E_02_0078 Immunohistochemistry and in situ hybridization experiments, enzyme-linked immunosorbent assay (ELISA), cell transfection, stimulation and luciferase assays, RNA extraction and quantitative RT-PCR, protein extracts and Western blotting, electrophoretic mobility shift assay (EMSA), flow cytometry and forming unit erythroid (CFU-E) assays, chromatin immunoprecipitation (chip) and ATAC qPCR assays were performed In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Immunohistochemical staining In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. 免疫组化和原位杂交实验，酶联免疫吸附测定（ELISA），细胞转染、刺激和荧光素酶检测，RNA 提取和定量 RT-PCR，蛋白质提取物和蛋白质印迹，电泳迁移率移位测定 （EMSA），流式细胞术和成形单元红系 （CFU-E） 检测，染色质免疫沉淀 （ChIP） 和 ATAC-qPCR 检测 ARID1A In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. 29593713 chr17 27054976 27056976 Nkx2-5 We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. mouse Musculature High+Lowthroughput Divergent Transcription of the Nkx2-5 Locus Generates Two Enhancer RNAs with Opposing Functions 否 heart failure cardiac muscle cell (sensu Arthopoda) E_02_0079 RNA sequencing (RNA SEQ), quantitative PCR (qPCR), cell fractionation, rna-fish, Western blotting, fluorescent immunoassay We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. Immunohistochemical staining We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. RNA测序（RNA-seq），定量PCR（qPCR），细胞分馏，RNA-FISH，蛋白质印记，荧光免疫分析 Nkx2-5 We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. 29592873 chr13 73052423 73054423 KLF5 These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. human connective High+Lowthroughput Regulation of adipocyte differentiation by clusterin-mediated Krüppel-like factor 5 stabilization 否 fat cell，mesenchymal stem cell E_02_0080 RNA isolation and quantitative real_x0002_time PCR (qRT-PCR)，Luciferase reporter assay，20S proteasome activity assay These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. Immunohistochemical staining These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. RNA isolation and quantitative real_x0002_time PCR (qRT-PCR)，Luciferase reporter assay，20S proteasome activity assay KLF5 These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. 29583017 chr6 47504032 47506032 Ezh2 Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. mouse Bone marrow High+Lowthroughput Hematopoietic stem/progenitor cell senescence is associated with altered expression profiles of cellular memory-involved gene 否 senescence associated disease progenitor cell E_02_0081 qRT-PCR Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. Immunohistochemical staining Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. qRT-PCR Ezh2 Ezh2 is a key member of the PcG family. It can promote the survival of HSCs. 29579159 chr15 61854370 61856370 Myc The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies mouse Haematopoietic High+Lowthroughput A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies 否 haematopoietic malignancies hematopoietic stem cell E_02_0082 RT–qPCR,ATAC-seq,RNA-seq, The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies Immunohistochemical staining The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies RT–qPCR,ATAC-seq,RNA-seq, Myc The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies 29568244 chr2 103785432 103787432 Lmo2 T controls the expression of Lmo2, a master regulator of hematopoietic and endothelial development mouse Embryo High+Lowthroughput BRACHYURY directs histone acetylation to target loci during mesoderm development 否 congenital diseases hematopoietic and endothelial cell E_02_0083 ChIP-Seq,RNA-Seq ,ChIP-qPCR T controls the expression of Lmo2, a master regulator of hematopoietic and endothelial development Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq T controls the expression of Lmo2, a master regulator of hematopoietic and endothelial development Immunohistochemical staining T controls the expression of Lmo2, a master regulator of hematopoietic and endothelial development ChIP-Seq,RNA-Seq ,ChIP-qPCR Lmo2 T controls the expression of Lmo2, a master regulator of hematopoietic and endothelial development 29564771 chr7 148804053 148806053 EZH2 EZH2 plays an important role in this inflammatory process of dental pulp. human dental pulp High+Lowthroughput EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors 否 dental pulp inflammation dental pulp cell E_02_0084 qPCR,ChIP,Western blot EZH2 plays an important role in this inflammatory process of dental pulp. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 plays an important role in this inflammatory process of dental pulp. Immunohistochemical staining EZH2 plays an important role in this inflammatory process of dental pulp. qPCR,ChIP,Western blot EZH2 EZH2 plays an important role in this inflammatory process of dental pulp. 29563192 chr16 67559679 67561679 CTCF The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. human High+Lowthroughput Stochastic Gene Choice during Cellular Differentiation 否 embryonic stem cell E_02_0085 Single-Cell qRT-PCR,Chromatin Immunoprecipitation,Bisulfite Sequencing The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. Immunohistochemical staining The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. Single-Cell qRT-PCR,Chromatin Immunoprecipitation,Bisulfite Sequencing CTCF The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. 29563115 chr17 42310596 42312596 STAT3 Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. human connective High+Lowthroughput Generation of Nanog reporter mice that distinguish pluripotent stem cells from unipotent primordial germ cells 否 pluripotent stem cell E_02_0086 PCR, flow cytometry, immunofluorescence staining Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. Immunohistochemical staining Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. PCR,Flow cytometry,免疫荧光染色 STAT3 Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. 29556394 chr8 144311848 144313848 DGAT1 Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. human High+Lowthroughput Butyric acid induces spontaneous adipocytic differentiation of porcine bone marrow-derived mesenchymal stem cells 否 mesenchymal stem cell E_02_0087 Proliferation study,Differentiation study,Differentiation study,Cytochemical staining Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. Immunohistochemical staining Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. Proliferation study,Differentiation study,Differentiation study,Cytochemical staining DGAT1,FAS,CPT2 Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study.;Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study.;Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. 29552163 chr2 132413869 132415869 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). human adipose High+Lowthroughput Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment. 否 Duchenne muscular dystrophy (DMD) satellite cell E_02_0088 Real ‐ time PCR, Weston blot, immunofluorescence staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Immunohistochemical staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). real‐time PCR,weston blot,免疫荧光染色 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). 29552153 chr2 132413957 132415957 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). human High+Lowthroughput Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment. 否 Duchenne muscular dystrophy (DMD) muscle cell E_02_0089 Real ‐ time PCR, Weston blot, immunofluorescence staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Immunohistochemical staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). real‐time PCR,weston blot,免疫荧光染色 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). 29540569 chr7 148804523 148806523 EZH2 We report a distinct mechanism whereby p53-regulated MDM2 works together with MDMX to modulate sensitivity to DNA damage by controlling EZH2 (enhancer of zeste homolog 2) turnover. human p53-dependent High+Lowthroughput An EZH2-mediated epigenetic mechanism behind p53-dependent tissue sensitivity to DNA damage 否 Cancer cell E_02_0090 qRT-PCR. We report a distinct mechanism whereby p53-regulated MDM2 works together with MDMX to modulate sensitivity to DNA damage by controlling EZH2 (enhancer of zeste homolog 2) turnover. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We report a distinct mechanism whereby p53-regulated MDM2 works together with MDMX to modulate sensitivity to DNA damage by controlling EZH2 (enhancer of zeste homolog 2) turnover. Immunohistochemical staining We report a distinct mechanism whereby p53-regulated MDM2 works together with MDMX to modulate sensitivity to DNA damage by controlling EZH2 (enhancer of zeste homolog 2) turnover. qRT-PCR. EZH2 We report a distinct mechanism whereby p53-regulated MDM2 works together with MDMX to modulate sensitivity to DNA damage by controlling EZH2 (enhancer of zeste homolog 2) turnover. 29535816 chr4 108044694 108046694 LEF1 The transcription factor lymphoid enhancer factor 1 (LEF1) and the secreted ligand WNT5A, expressed in NPC, were increased in EBV-infected NOK with sustained expression for more than 20 passages after viral loss. Increased LEF1 levels involved four LEF1 variants, and EBV-infected NOK showed a lack of responsiveness to 尾-catenin activation. Although forced expression of WNT5A and LEF1 enhanced the invasiveness of parental NOK, LEF1 knockdown reversed the invasive phenotype of EBV-infected NOK in the presence of WNT5A. human High+Lowthroughput Epstein-Barr virus stably confers an invasive phenotype to epithelial cells through reprogramming of the WNT pathway 否 gastric cancer cell E_02_0091 RT-qPCR The transcription factor lymphoid enhancer factor 1 (LEF1) and the secreted ligand WNT5A, expressed in NPC, were increased in EBV-infected NOK with sustained expression for more than 20 passages after viral loss. Increased LEF1 levels involved four LEF1 variants, and EBV-infected NOK showed a lack of responsiveness to 尾-catenin activation. Although forced expression of WNT5A and LEF1 enhanced the invasiveness of parental NOK, LEF1 knockdown reversed the invasive phenotype of EBV-infected NOK in the presence of WNT5A. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcription factor lymphoid enhancer factor 1 (LEF1) and the secreted ligand WNT5A, expressed in NPC, were increased in EBV-infected NOK with sustained expression for more than 20 passages after viral loss. Increased LEF1 levels involved four LEF1 variants, and EBV-infected NOK showed a lack of responsiveness to 尾-catenin activation. Although forced expression of WNT5A and LEF1 enhanced the invasiveness of parental NOK, LEF1 knockdown reversed the invasive phenotype of EBV-infected NOK in the presence of WNT5A. Immunohistochemical staining The transcription factor lymphoid enhancer factor 1 (LEF1) and the secreted ligand WNT5A, expressed in NPC, were increased in EBV-infected NOK with sustained expression for more than 20 passages after viral loss. Increased LEF1 levels involved four LEF1 variants, and EBV-infected NOK showed a lack of responsiveness to 尾-catenin activation. Although forced expression of WNT5A and LEF1 enhanced the invasiveness of parental NOK, LEF1 knockdown reversed the invasive phenotype of EBV-infected NOK in the presence of WNT5A. RT-qPCR LEF1 The transcription factor lymphoid enhancer factor 1 (LEF1) and the secreted ligand WNT5A, expressed in NPC, were increased in EBV-infected NOK with sustained expression for more than 20 passages after viral loss. Increased LEF1 levels involved four LEF1 variants, and EBV-infected NOK showed a lack of responsiveness to 尾-catenin activation. Although forced expression of WNT5A and LEF1 enhanced the invasiveness of parental NOK, LEF1 knockdown reversed the invasive phenotype of EBV-infected NOK in the presence of WNT5A. 29534682 chrX 21370203 21372203 CNKSR2 The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. human High+Lowthroughput Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression 否 E_02_0092 RT-PCR The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. Immunohistochemical staining The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. RT-PCR CNKSR2 The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. 29533787 chr2 132414173 132416173 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). human High+Lowthroughput Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment. 否 muscle cell E_02_0093 Real ‐ time PCR, Weston blot, immunofluorescence staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Immunohistochemical staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). real‐time PCR,weston blot,免疫荧光染色 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). 29531042 chr2 42492054 42494054 MTA3 The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. human Epithelial High+Lowthroughput Acute and Cumulative Effects of Haze Fine Particles on Mortality and the Seasonal Characteristics in Beijing, China, 2005-2013: A Time-Stratified Case-Crossover Study 否 endothelial cell E_02_0094 PCR, Western blot, gel electrophoresis The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. Immunohistochemical staining The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. PCR,Western blot,凝胶电泳 MTA3 The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. 29531012 chr6 36591744 36593744 SRSF3 SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. human kidney High+Lowthroughput The ameliorative effect of Protaetia brevitarsis Larvae in HFD-induced obese mice 否 HEK293T cell E_02_0095 Western blot, gel electrophoresis, clip seq SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Immunohistochemical staining SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Western blot,凝胶电泳,CLIP-seq SRSF3 SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. 29530927 chr12 113389472 113391472 SDS Equal amounts (20 _xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. human High+Lowthroughput Dephosphorylation of HDAC4 by PP2A-Bδ unravels a new role for the HDAC4/MEF2 axis in myoblast fusion 否 mesenchymal stem cell E_02_0096 PCR, Western blot, gel electrophoresis Equal amounts (20 _xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Equal amounts (20 _xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. Immunohistochemical staining Equal amounts (20 _xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. PCR,Western blot,凝胶电泳 SDS Equal amounts (20 _xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. 29529279 chr8 94246645 94248645 GEM In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). human liver High+Lowthroughput Toll-like receptor 2 stimulation augments esophageal barrier integrity 否 Huh 7 cell E_02_0097 PCR, flow cytometry, gene knockdown, Western blot, gel electrophoresis, immunofluorescence staining In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). Immunohistochemical staining In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). PCR,流式细胞术,基因敲降,Western blot,凝胶电泳,免疫荧光染色 GEM In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). 29525407 chr7 148804989 148806989 EZH2 It was shown that O-GlcNAcylation stabilizes histone methyltransferase enhancer of zeste homolog 2 (EZH2), which facilitates the formation of the trimethylation of histone 3 at lysine 27 (H3K27me3) thereby repressing gene expression in human MCF-7 cells [41]. human adipose High+Lowthroughput Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity 否 E_02_0098 qPCR It was shown that O-GlcNAcylation stabilizes histone methyltransferase enhancer of zeste homolog 2 (EZH2), which facilitates the formation of the trimethylation of histone 3 at lysine 27 (H3K27me3) thereby repressing gene expression in human MCF-7 cells [41]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It was shown that O-GlcNAcylation stabilizes histone methyltransferase enhancer of zeste homolog 2 (EZH2), which facilitates the formation of the trimethylation of histone 3 at lysine 27 (H3K27me3) thereby repressing gene expression in human MCF-7 cells [41]. Immunohistochemical staining It was shown that O-GlcNAcylation stabilizes histone methyltransferase enhancer of zeste homolog 2 (EZH2), which facilitates the formation of the trimethylation of histone 3 at lysine 27 (H3K27me3) thereby repressing gene expression in human MCF-7 cells [41]. qPCR EZH2 It was shown that O-GlcNAcylation stabilizes histone methyltransferase enhancer of zeste homolog 2 (EZH2), which facilitates the formation of the trimethylation of histone 3 at lysine 27 (H3K27me3) thereby repressing gene expression in human MCF-7 cells [41]. 29521509 chr7 116522460 116524460 CAV1 CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. human lymphoid High+Lowthroughput Rare Variant Burden Analysis within Enhancers Identifies CAV1 as an ALS Risk Gene 否 Lymphoblast E_02_0099 Immunoblotting, fluorescent quantitative PCR (RT-PCR), immunocytochemistry, live cell imaging CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. Immunohistochemical staining CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. 免疫印迹，荧光定量 PCR（RT-PCR），免疫细胞化学，活细胞成像 CAV1 CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. 29515369 chr1 145668268 145670268 PDZK1 siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. human High+Lowthroughput A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression 否 rs1967017,rs1471633 hyperuricemia HepG2 cell E_02_0100 Quantitative PCR, immunoblot analysis, chip PCR, statistical analysis, Weston blot siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Immunohistochemical staining siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Quantitative PCR,Immunoblot analysis, ChIP-PCR,统计分析,weston blot PDZK1,HNF4A siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. ; siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. 29514910 chr11 73215408 73217408 P2RY2 P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. human High+Lowthroughput Enhancer RNA - P2RY2e induced by estrogen promotes malignant behaviors of bladder cancer 否 Breast, bladder, stomach, pancreas, prostate, lung T24 cell E_02_0101 RT qPCR, flow cytometry, ELISA, statistical analysis P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. Immunohistochemical staining P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. RT-qPCR,流式细胞术,ELISA,统计分析 P2RY2 P2RY2 enhancer RNA (P2RY2e) is an estrogen-responsive eRNA and involved in the development of breast cancer. 29514101 chrX 67541320 67543320 AR For example, one human AR is an enhancer with putative roles in the evolution of the human thumb (Prabhakar et al., 2008). human High+Lowthroughput Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance 否 E_02_0102 DNase-seq For example, one human AR is an enhancer with putative roles in the evolution of the human thumb (Prabhakar et al., 2008). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For example, one human AR is an enhancer with putative roles in the evolution of the human thumb (Prabhakar et al., 2008). Immunohistochemical staining For example, one human AR is an enhancer with putative roles in the evolution of the human thumb (Prabhakar et al., 2008). DNase-seq AR For example, one human AR is an enhancer with putative roles in the evolution of the human thumb (Prabhakar et al., 2008). 29899112 chr6 47504499 47506499 Ezh2 Hence, genetic loss of Ezh2 in mouse pre-osteoblasts inhibits osteogenesis in part by inducing cell cycle changes. Our results suggest that Ezh2 serves a bifunctional role during bone formation by suppressing osteogenic lineage commitment while simultaneously facilitating proliferative expansion of osteoprogenitor cells. mouse Nervous High+Lowthroughput Enhancer of zeste homolog 2 (Ezh2) controls bone formation and cell cycle progression during osteogenesis in mice 否 mesenchymal stem cell of the bone marrow E_02_0103 RNA-Seq,Western blot,staining,RT-qPCR,MTS assays,Flow cytometric analysis,Ex vivo assays,Histology,histomorphometric analysis,Micro-computed tomography analysis,Alkaline Phosphatase and Alizarin Red Staining,Hoechst staining, Hence, genetic loss of Ezh2 in mouse pre-osteoblasts inhibits osteogenesis in part by inducing cell cycle changes. Our results suggest that Ezh2 serves a bifunctional role during bone formation by suppressing osteogenic lineage commitment while simultaneously facilitating proliferative expansion of osteoprogenitor cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hence, genetic loss of Ezh2 in mouse pre-osteoblasts inhibits osteogenesis in part by inducing cell cycle changes. Our results suggest that Ezh2 serves a bifunctional role during bone formation by suppressing osteogenic lineage commitment while simultaneously facilitating proliferative expansion of osteoprogenitor cells. Immunohistochemical staining Hence, genetic loss of Ezh2 in mouse pre-osteoblasts inhibits osteogenesis in part by inducing cell cycle changes. Our results suggest that Ezh2 serves a bifunctional role during bone formation by suppressing osteogenic lineage commitment while simultaneously facilitating proliferative expansion of osteoprogenitor cells. RNA-Seq,Western blot,staining,RT-qPCR,MTS assays,Flow cytometric analysis,Ex vivo assays,Histology,histomorphometric analysis,Micro-computed tomography analysis,Alkaline Phosphatase and Alizarin Red Staining,Hoechst staining, Ezh2 Hence, genetic loss of Ezh2 in mouse pre-osteoblasts inhibits osteogenesis in part by inducing cell cycle changes. Our results suggest that Ezh2 serves a bifunctional role during bone formation by suppressing osteogenic lineage commitment while simultaneously facilitating proliferative expansion of osteoprogenitor cells. 29898989 chr3 36999364 37001216 CTCF A CTCF-bound region within the MLH1-35 enhancer regulates MLH1 expression in colorectal cells and is worthy of scrutiny in future genetic screening strategies for suspected Lynch syndrome associated with loss of MLH1 expression. human Connective Low throughput Disruption of a -35 kb Enhancer Impairs CTCF Binding and MLH1 Expression in Colorectal Cells 否 Lynch Syndrome E_02_0104 ChIP-qPCR,3C,Luciferase Reporter Assay,CRISPR/Cas9 We provide the first description of an enhancer for the MLH1 gene. This -35kb enhancer was CTCF-bound, and disruption of the consensus binding site within the enhancer significantly impairs MLH1 expression in SW620 colorectal carcinoma cells. Enhancer 3C,CRISPR/Cas9 ChIP-qPCR,Luciferase Reporter Assay COCA2,FCC2,HNPCC,HNPCC2,hMLH1 -- -- -- MRD21 CRISPR/Cas9 -- -- MLH1,MLH1 CTCF,CTCF We deleted a DNA fragment corresponding to the -35kb region from SW620 cells,showed that the -35kb region functions as an MLH1 Enhancer in SW620 colorectal cells.;We deleted a DNA fragment corresponding to the -35kb region from SW620 cells,showed that the -35kb region functions as an MLH1 Enhancer in SW620 colorectal cells. To evaluate the impact on endogenous MLH1 expression, we next deleted a region containing the CTCF binding motif in SW620 and K562 cells using CRISPR-Cas9 (Fig 3A, ΔCTCF). Similar to deletion of the entire Enhancer, we noted significant reduction in MLH1 expression in SW620 but not in K562 cells.;To evaluate the impact on endogenous MLH1 expression, we next deleted a region containing the CTCF binding motif in SW620 and K562 cells using CRISPR-Cas9 (Fig 3A, ΔCTCF). Similar to deletion of the entire Enhancer, we noted significant reduction in MLH1 expression in SW620 but not in K562 cells. 29510148 chr14 30871809 30873809 COCH COCH is the most abundantly expressed gene in the cochlea. human High+Lowthroughput Novel loss-of-function mutations in COCH cause autosomal recessive nonsyndromic hearing loss 否 MDCK cell E_02_0105 RT-PCR，PCR COCH is the most abundantly expressed gene in the cochlea. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq COCH is the most abundantly expressed gene in the cochlea. Immunohistochemical staining COCH is the most abundantly expressed gene in the cochlea. RT-PCR，PCR COCH COCH is the most abundantly expressed gene in the cochlea. 29503092 chr14 100235564 100237564 YY1 We sorted YY1 peaks by H3K4me1 and H3K4me3 to distinguish enhancers from promoters, and observed that both enhancer and promoter regions enriched for YY1 were co-bound by SMARCA4 and OSN (Figure 5D). human adult High+Lowthroughput YY1 Positively Regulates Transcription by Targeting Promoters and Super-Enhancers through the BAF Complex in Embryonic Stem Cells 否 pre-B cell E_02_0106 qPCR We sorted YY1 peaks by H3K4me1 and H3K4me3 to distinguish enhancers from promoters, and observed that both enhancer and promoter regions enriched for YY1 were co-bound by SMARCA4 and OSN (Figure 5D). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We sorted YY1 peaks by H3K4me1 and H3K4me3 to distinguish enhancers from promoters, and observed that both enhancer and promoter regions enriched for YY1 were co-bound by SMARCA4 and OSN (Figure 5D). Immunohistochemical staining We sorted YY1 peaks by H3K4me1 and H3K4me3 to distinguish enhancers from promoters, and observed that both enhancer and promoter regions enriched for YY1 were co-bound by SMARCA4 and OSN (Figure 5D). qPCR YY1 We sorted YY1 peaks by H3K4me1 and H3K4me3 to distinguish enhancers from promoters, and observed that both enhancer and promoter regions enriched for YY1 were co-bound by SMARCA4 and OSN (Figure 5D). 31221974 chr7 148804781 148806781 EZH2 We have previously shown that the Enhancer-of-zeste-like protein Ezl1 is essential for programmed DNA elimination and viability of the sexual progeny 25 . Here, we provide evidence that, Paramecium Ezl1, which exhibits significant sequence and structural similarities with human EZH2, displays distinct enzy- matic properties. human connective High+Lowthroughput The Polycomb protein Ezl1 mediates H3K9 and H3K27 methylation to repress transposable elements in Paramecium 否 embryonic stem cell E_02_0107 PCR We have previously shown that the Enhancer-of-zeste-like protein Ezl1 is essential for programmed DNA elimination and viability of the sexual progeny 25 . Here, we provide evidence that, Paramecium Ezl1, which exhibits significant sequence and structural similarities with human EZH2, displays distinct enzy- matic properties. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have previously shown that the Enhancer-of-zeste-like protein Ezl1 is essential for programmed DNA elimination and viability of the sexual progeny 25 . Here, we provide evidence that, Paramecium Ezl1, which exhibits significant sequence and structural similarities with human EZH2, displays distinct enzy- matic properties. Immunohistochemical staining We have previously shown that the Enhancer-of-zeste-like protein Ezl1 is essential for programmed DNA elimination and viability of the sexual progeny 25 . Here, we provide evidence that, Paramecium Ezl1, which exhibits significant sequence and structural similarities with human EZH2, displays distinct enzy- matic properties. PCR EZH2 We have previously shown that the Enhancer-of-zeste-like protein Ezl1 is essential for programmed DNA elimination and viability of the sexual progeny 25 . Here, we provide evidence that, Paramecium Ezl1, which exhibits significant sequence and structural similarities with human EZH2, displays distinct enzy- matic properties. 31217031 chr1 26690366 26692366 ARID1A We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. human connective High+Lowthroughput ARID1A facilitates KRAS signaling-regulated?enhancer activity in an AP1-dependent manner in colorectal cancer cells 否 tumor cell E_02_0108 PCR We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. Immunohistochemical staining We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. PCR ARID1A We identify a previously unknown context-dependent tumor-supporting function of ARID1A in CRC downstream of KRAS signaling. 31205561 chr7 148804432 148806432 EZH2 Enhancer of zeste homolog 2 (EZH2) and Bcl-2 gene rearrangement or protein upregulation played pivotal roles in the carcinogenesis of various malignancies including lymphomas. human connective High+Lowthroughput EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions 否 tumour tumor cell E_02_0109 PCR Enhancer of zeste homolog 2 (EZH2) and Bcl-2 gene rearrangement or protein upregulation played pivotal roles in the carcinogenesis of various malignancies including lymphomas. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) and Bcl-2 gene rearrangement or protein upregulation played pivotal roles in the carcinogenesis of various malignancies including lymphomas. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) and Bcl-2 gene rearrangement or protein upregulation played pivotal roles in the carcinogenesis of various malignancies including lymphomas. PCR EZH2 Enhancer of zeste homolog 2 (EZH2) and Bcl-2 gene rearrangement or protein upregulation played pivotal roles in the carcinogenesis of various malignancies including lymphomas. 31202798 chr7 148804013 148806013 EZH2 Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been recognized to play a pivotal role in regulating the immune response in various diseases. human connective High+Lowthroughput EZH2 inhibitor DZNep modulates microglial activation and protects against ischaemic brain injury after experimental stroke 否 microglial cell E_02_0110 PCR Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been recognized to play a pivotal role in regulating the immune response in various diseases. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been recognized to play a pivotal role in regulating the immune response in various diseases. Immunohistochemical staining Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been recognized to play a pivotal role in regulating the immune response in various diseases. PCR EZH2 Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been recognized to play a pivotal role in regulating the immune response in various diseases. 31201420 chr7 148804563 148806563 EZH2 In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function human connective High+Lowthroughput The histone methyltransferase EZH2 is required for normal uterine development and function in mice? 否 epithelial cell of uterus E_02_0111 PCR In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function Immunohistochemical staining In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function PCR EZH2 In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy and cystic endometrial hyperplasia, indicating a critical role in uterine development and function 31176714 chr18 63868870 63870870 SERPINB2 However, the further analysis demonstrated that the expression of the enhancer RNA encoded by the region of DNA 20 kbp upstream from the SERPINB2 gene was AhR-dependent human connective High+Lowthroughput Expression of Serpin Peptidase Inhibitor B2 (SERPINB2) is regulated by Aryl hydrocarbon receptor (AhR) 否 tumour tumor cell E_02_0112 PCR However, the further analysis demonstrated that the expression of the enhancer RNA encoded by the region of DNA 20 kbp upstream from the SERPINB2 gene was AhR-dependent Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, the further analysis demonstrated that the expression of the enhancer RNA encoded by the region of DNA 20 kbp upstream from the SERPINB2 gene was AhR-dependent Immunohistochemical staining However, the further analysis demonstrated that the expression of the enhancer RNA encoded by the region of DNA 20 kbp upstream from the SERPINB2 gene was AhR-dependent PCR SERPINB2 However, the further analysis demonstrated that the expression of the enhancer RNA encoded by the region of DNA 20 kbp upstream from the SERPINB2 gene was AhR-dependent 31173852 chr5 132437801 132439801 IRF1 In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1 human connective High+Lowthroughput Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response 否 ESCC Esophageal squamous cell carcinoma cell E_02_0113 PCR In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1 Immunohistochemical staining In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1 PCR IRF1 In conclusion, the interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma progression by promoting interferon response through a positive regulatory loop with IRF1 31164154 chr4 105142775 105144775 TET2 Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2. human connective High+Lowthroughput Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation 否 myocyte E_02_0114 PCR Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2. Immunohistochemical staining Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2. PCR TET2 Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2. 31141090 chr19 33297251 33299251 CEBPA Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). human connective High+Lowthroughput CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice 否 hematopoietic stem cell E_02_0115 PCR Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). Immunohistochemical staining Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). PCR CEBPA Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). 31064204 chr19 33297418 33299418 CEBPA In this study, the coding domain sequences (CDS) of pigeon C/EBP-α and βwere cloned, human connective High+Lowthroughput Molecular cloning, characterisation, and expression patterns of pigeon CCAAT/enhancer binding protein-α and -β genes 否 cancer cancer cell E_02_0116 PCR In this study, the coding domain sequences (CDS) of pigeon C/EBP-α and βwere cloned, Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, the coding domain sequences (CDS) of pigeon C/EBP-α and βwere cloned, Immunohistochemical staining In this study, the coding domain sequences (CDS) of pigeon C/EBP-α and βwere cloned, PCR CEBPA In this study, the coding domain sequences (CDS) of pigeon C/EBP-α and βwere cloned, 31719045 chr13 63653269 63655269 Ptch1 We confirmed that, in comparison to wild-type (WT) littermates, SHH signalling was significantly decreased in the developing tongue of ShhMFCS4/− mice by E11.5, as demonstrated by reduced Shh and patched 1 (Ptch1) expression (Fig. 1A-D) and consistent with the known period of MFCS4 activity (Sagai et al., 2009). mouse Musculature High+Lowthroughput Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature 否 muscle precursor cell E_02_0117 PCR、Western blot We confirmed that, in comparison to wild-type (WT) littermates, SHH signalling was significantly decreased in the developing tongue of ShhMFCS4/− mice by E11.5, as demonstrated by reduced Shh and patched 1 (Ptch1) expression (Fig. 1A-D) and consistent with the known period of MFCS4 activity (Sagai et al., 2009). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We confirmed that, in comparison to wild-type (WT) littermates, SHH signalling was significantly decreased in the developing tongue of ShhMFCS4/− mice by E11.5, as demonstrated by reduced Shh and patched 1 (Ptch1) expression (Fig. 1A-D) and consistent with the known period of MFCS4 activity (Sagai et al., 2009). Immunohistochemical staining We confirmed that, in comparison to wild-type (WT) littermates, SHH signalling was significantly decreased in the developing tongue of ShhMFCS4/− mice by E11.5, as demonstrated by reduced Shh and patched 1 (Ptch1) expression (Fig. 1A-D) and consistent with the known period of MFCS4 activity (Sagai et al., 2009). PCR、Western blot Ptch1 We confirmed that, in comparison to wild-type (WT) littermates, SHH signalling was significantly decreased in the developing tongue of ShhMFCS4/− mice by E11.5, as demonstrated by reduced Shh and patched 1 (Ptch1) expression (Fig. 1A-D) and consistent with the known period of MFCS4 activity (Sagai et al., 2009). 31718447 chr9 117701356 117703356 TLR4 Activation of the TLR4 signaling pathway is initiated by the binding of its ligands to TLR4, causing TLR4 to relocate to lipid rafts, and then forming TLR4/myeloid differentiation factor 2 (MD2) complex in lipid rafts, leading to activation of nuclear factorkappa-light-chain-enhancer of activated B cells (NF-jB)and overproduction of proinflammatory cytokines. human connective High+Lowthroughput Sphingomyelin Synthase 2 Inhibition Ameliorates Cerebral Ischemic Reperfusion Injury Through Reducing the Recruitment of Toll-Like Receptor 4 to Lipid Rafts 否 cerebral ischemia B cell E_02_0118 PCR、Western blot Activation of the TLR4 signaling pathway is initiated by the binding of its ligands to TLR4, causing TLR4 to relocate to lipid rafts, and then forming TLR4/myeloid differentiation factor 2 (MD2) complex in lipid rafts, leading to activation of nuclear factorkappa-light-chain-enhancer of activated B cells (NF-jB)and overproduction of proinflammatory cytokines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Activation of the TLR4 signaling pathway is initiated by the binding of its ligands to TLR4, causing TLR4 to relocate to lipid rafts, and then forming TLR4/myeloid differentiation factor 2 (MD2) complex in lipid rafts, leading to activation of nuclear factorkappa-light-chain-enhancer of activated B cells (NF-jB)and overproduction of proinflammatory cytokines. Immunohistochemical staining Activation of the TLR4 signaling pathway is initiated by the binding of its ligands to TLR4, causing TLR4 to relocate to lipid rafts, and then forming TLR4/myeloid differentiation factor 2 (MD2) complex in lipid rafts, leading to activation of nuclear factorkappa-light-chain-enhancer of activated B cells (NF-jB)and overproduction of proinflammatory cytokines. PCR、Western blot TLR4,TLR5 Activation of the TLR4 signaling pathway is initiated by the binding of its ligands to TLR4, causing TLR4 to relocate to lipid rafts, and then forming TLR4/myeloid differentiation factor 2 (MD2) complex in lipid rafts, leading to activation of nuclear factorkappa-light-chain-enhancer of activated B cells (NF-jB)and overproduction of proinflammatory cytokines.;Activation of the TLR4 signaling pathway is initiated by the binding of its ligands to TLR4, causing TLR4 to relocate to lipid rafts, and then forming TLR4/myeloid differentiation factor 2 (MD3) complex in lipid rafts, leading to activation of nuclear factorkappa-light-chain-enhancer of activated B cells (NF-jB)and overproduction of proinflammatory cytokines. 31718444 chr3 43283601 43285601 SNRK The SNRK (sucrose-nonfermenting–related kinase) enzyme is critical for cardiac function. human connective High+Lowthroughput Cardiomyocyte-Specific Snrk Prevents Inflammation in the Heart 否 cancer B cell E_02_0119 PCR、Western blot The SNRK (sucrose-nonfermenting–related kinase) enzyme is critical for cardiac function. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The SNRK (sucrose-nonfermenting–related kinase) enzyme is critical for cardiac function. Immunohistochemical staining The SNRK (sucrose-nonfermenting–related kinase) enzyme is critical for cardiac function. PCR、Western blot SNRK The SNRK (sucrose-nonfermenting–related kinase) enzyme is critical for cardiac function. 31714653 chrX 123856867 123858867 XIAP In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. human connective High+Lowthroughput Apoptosis induction and ERK/NF-κB inactivation are associated with magnolol-inhibited tumor progression in hepatocellular carcinoma in vivo 否 liver cancer B cell E_02_0120 PCR In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. Immunohistochemical staining In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. PCR XIAP In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. 31713877 chr17 27753488 27755488 NOS2 Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS-induced mouse model (25, 26). Sarpogrelate decreased immune cell infiltration and NOS2 and TNF expression in diabetic mice. human connective High+Lowthroughput Comparative effectiveness of different antiplatelet agents at reducing TNF-driven inflammatory responses in a mouse model 否 Ischemic disease immune cell E_02_0121 PCR、Western blot Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS-induced mouse model (25, 26). Sarpogrelate decreased immune cell infiltration and NOS2 and TNF expression in diabetic mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS-induced mouse model (25, 26). Sarpogrelate decreased immune cell infiltration and NOS2 and TNF expression in diabetic mice. Immunohistochemical staining Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS-induced mouse model (25, 26). Sarpogrelate decreased immune cell infiltration and NOS2 and TNF expression in diabetic mice. PCR、Western blot NOS2,NOS3 Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS-induced mouse model (25, 26). Sarpogrelate decreased immune cell infiltration and NOS2 and TNF expression in diabetic mice.;Clopidogrel reduced serum TNF and IL‐1β release in rats with coronary microembolization and experimental LPS-induced mouse model (25, 26). Sarpogrelate decreased immune cell infiltration and NOS3 and TNF expression in diabetic mice. 31712448 chr11 108808163 108810163 Axin2 In contrast, the expression of Axin2 and Ccdc80 was strongly up-regulated in Wnt3a-treated HNF-1β mutant cells compared to wild-type cells mouse Epithelial High+Lowthroughput Hepatocyte nuclear factor-1β regulates Wnt signaling through genome-wide competition with β-catenin/lymphoid enhancer binding factor 否 Cystic kidney disease epithelial cell E_02_0122 In contrast, the expression of Axin2 and Ccdc80 was strongly up-regulated in Wnt3a-treated HNF-1β mutant cells compared to wild-type cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In contrast, the expression of Axin2 and Ccdc80 was strongly up-regulated in Wnt3a-treated HNF-1β mutant cells compared to wild-type cells Immunohistochemical staining In contrast, the expression of Axin2 and Ccdc80 was strongly up-regulated in Wnt3a-treated HNF-1β mutant cells compared to wild-type cells Axin2,Ccdc80 In contrast, the expression of Axin2 and Ccdc80 was strongly up-regulated in Wnt3a-treated HNF-1β mutant cells compared to wild-type cells;In contrast, the expression of Axin2 and Ccdc80 was strongly up-regulated in Wnt3a-treated HNF-1β mutant cells compared to wild-type cells 31712269 chr3 52218227 52220227 TLR9 pylori-induced NF-κB activation and IL-8 secretion are attributed to T4SS-dependent delivery of lipopolysaccharide metabolites and peptidoglycan into host cells, and Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA. human stomach High+Lowthroughput Bacterial Energetic Requirements for Helicobacter pylori Cag Type IV Secretion System-Dependent Alterations in Gastric Epithelial Cells 否 cancer epithelial cell of stomach E_02_0123 pylori-induced NF-κB activation and IL-8 secretion are attributed to T4SS-dependent delivery of lipopolysaccharide metabolites and peptidoglycan into host cells, and Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq pylori-induced NF-κB activation and IL-8 secretion are attributed to T4SS-dependent delivery of lipopolysaccharide metabolites and peptidoglycan into host cells, and Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA. Immunohistochemical staining pylori-induced NF-κB activation and IL-8 secretion are attributed to T4SS-dependent delivery of lipopolysaccharide metabolites and peptidoglycan into host cells, and Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA. TLR9 pylori-induced NF-κB activation and IL-8 secretion are attributed to T4SS-dependent delivery of lipopolysaccharide metabolites and peptidoglycan into host cells, and Toll-like receptor 9 (TLR9) activation is attributed to delivery of bacterial DNA. 31711897 chr14 54839063 54841063 GCH1 GCH1 feedback regulatory protein (GFRP) inhibits GCH1 activity when BH4 levels increase [14]; dihydropteridin reductase (DHPR) and dihydrofolate reductase (DHFR) ensure the re_x0002_cycling of dihydrobiopterin (BH2) into BH4 [15], BH2 being an oxi_x0002_dized and inactive form of BH4. human High+Lowthroughput Tetrahydrobiopterin administration facilitates amphetamine-induced dopamine release and motivation in mice 否 E_02_0124 PCR,Western blot GCH1 feedback regulatory protein (GFRP) inhibits GCH1 activity when BH4 levels increase [14]; dihydropteridin reductase (DHPR) and dihydrofolate reductase (DHFR) ensure the re_x0002_cycling of dihydrobiopterin (BH2) into BH4 [15], BH2 being an oxi_x0002_dized and inactive form of BH4. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GCH1 feedback regulatory protein (GFRP) inhibits GCH1 activity when BH4 levels increase [14]; dihydropteridin reductase (DHPR) and dihydrofolate reductase (DHFR) ensure the re_x0002_cycling of dihydrobiopterin (BH2) into BH4 [15], BH2 being an oxi_x0002_dized and inactive form of BH4. Immunohistochemical staining GCH1 feedback regulatory protein (GFRP) inhibits GCH1 activity when BH4 levels increase [14]; dihydropteridin reductase (DHPR) and dihydrofolate reductase (DHFR) ensure the re_x0002_cycling of dihydrobiopterin (BH2) into BH4 [15], BH2 being an oxi_x0002_dized and inactive form of BH4. PCR,Western blot GCH1 GCH1 feedback regulatory protein (GFRP) inhibits GCH1 activity when BH4 levels increase [14]; dihydropteridin reductase (DHPR) and dihydrofolate reductase (DHFR) ensure the re_x0002_cycling of dihydrobiopterin (BH2) into BH4 [15], BH2 being an oxi_x0002_dized and inactive form of BH4. 31711520 chr7 148804473 148806473 EZH2 We noticed that enhancer of zeste homologue 2 (EZH2) could afect the self-renewal and dif_x0002_ferentiation of hematopoietic stem cells [5] and may be an independent prognostic factor [6] related to a poor progno_x0002_sis [7]. human connective High+Lowthroughput HO-1 promotes resistance to an EZH2 inhibitor through the pRB-E2F pathway: correlation with the progression of myelodysplastic syndrome into acute myeloid leukemia 否 leukemia tumor cell E_02_0125 PCR, Western blot, immunofluorescence staining We noticed that enhancer of zeste homologue 2 (EZH2) could afect the self-renewal and dif_x0002_ferentiation of hematopoietic stem cells [5] and may be an independent prognostic factor [6] related to a poor progno_x0002_sis [7]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We noticed that enhancer of zeste homologue 2 (EZH2) could afect the self-renewal and dif_x0002_ferentiation of hematopoietic stem cells [5] and may be an independent prognostic factor [6] related to a poor progno_x0002_sis [7]. Immunohistochemical staining We noticed that enhancer of zeste homologue 2 (EZH2) could afect the self-renewal and dif_x0002_ferentiation of hematopoietic stem cells [5] and may be an independent prognostic factor [6] related to a poor progno_x0002_sis [7]. PCR,Western blot,免疫荧光染色 EZH2 We noticed that enhancer of zeste homologue 2 (EZH2) could afect the self-renewal and dif_x0002_ferentiation of hematopoietic stem cells [5] and may be an independent prognostic factor [6] related to a poor progno_x0002_sis [7]. 31709534 chr1 164552565 164554565 PBX1 Low Nfe2l1 mRNA expression is unlikely caused by reduced mTOR signaling but could be the result of diminished pre‐B‐cell leukemia homeobox-1 transcription factor (PBX1) levels. human connective High+Lowthroughput Decreased levels of constitutive proteasomes in experimental autoimmune encephalomyelitis may be caused by a combination of subunit displacement and reduced Nfe2l1 expression 否 inflammation B cell E_02_0126 PCR, Western blot, immunofluorescence staining Low Nfe2l1 mRNA expression is unlikely caused by reduced mTOR signaling but could be the result of diminished pre‐B‐cell leukemia homeobox-1 transcription factor (PBX1) levels. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Low Nfe2l1 mRNA expression is unlikely caused by reduced mTOR signaling but could be the result of diminished pre‐B‐cell leukemia homeobox-1 transcription factor (PBX1) levels. Immunohistochemical staining Low Nfe2l1 mRNA expression is unlikely caused by reduced mTOR signaling but could be the result of diminished pre‐B‐cell leukemia homeobox-1 transcription factor (PBX1) levels. PCR,Western blot,免疫荧光染色 PBX1 Low Nfe2l1 mRNA expression is unlikely caused by reduced mTOR signaling but could be the result of diminished pre‐B‐cell leukemia homeobox-1 transcription factor (PBX1) levels. 31709175 chr9 127084657 127086657 ANGPTL2 Relative gene expression intensity of ANGPTL2, EHMT1 FOXO1, HAP1, NUCKS1, NUP43, PIK3CG,RAPGEF5, SEMA6A, SPIN1, TRH, and WASF2 followed the pattern of change in the intensity of the expression of the F13A1 gene. human connective High+Lowthroughput Coagulation FXIII-A Protein Expression Defines Three Novel Sub-populations in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia Characterized by Distinct Gene Expression Signatures 否 leukemia B cell E_02_0127 PCR,Flow cytometry Relative gene expression intensity of ANGPTL2, EHMT1 FOXO1, HAP1, NUCKS1, NUP43, PIK3CG,RAPGEF5, SEMA6A, SPIN1, TRH, and WASF2 followed the pattern of change in the intensity of the expression of the F13A1 gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Relative gene expression intensity of ANGPTL2, EHMT1 FOXO1, HAP1, NUCKS1, NUP43, PIK3CG,RAPGEF5, SEMA6A, SPIN1, TRH, and WASF2 followed the pattern of change in the intensity of the expression of the F13A1 gene. Immunohistochemical staining Relative gene expression intensity of ANGPTL2, EHMT1 FOXO1, HAP1, NUCKS1, NUP43, PIK3CG,RAPGEF5, SEMA6A, SPIN1, TRH, and WASF2 followed the pattern of change in the intensity of the expression of the F13A1 gene. PCR,Flow cytometry ANGPTL2,RAPGEF5,CCL5,IL7R,CX3CR1 Relative gene expression intensity of ANGPTL2, EHMT1 FOXO1, HAP1, NUCKS1, NUP43, PIK3CG,RAPGEF5, SEMA6A, SPIN1, TRH, and WASF2 followed the pattern of change in the intensity of the expression of the F13A1 gene.;Relative gene expression intensity of ANGPTL2, EHMT1 FOXO1, HAP1, NUCKS1, NUP43, PIK3CG,RAPGEF5, SEMA6A, SPIN1, TRH, and WASF2 followed the pattern of change in the intensity of the expression of the F13A1 gene.;Genes involved in lymphocyte and T-cell apoptotic processes (CCL5, CD3G,IL7R, PLAC8) were over-presented, as well as two others,CX3CR1, RORA, corresponding to macrophage migration.;Genes involved in lymphocyte and T-cell apoptotic processes (CCL5, CD3G,IL7R, PLAC8) were over-presented, as well as two others,CX3CR1, RORA, corresponding to macrophage migration.;Genes involved in lymphocyte and T-cell apoptotic processes (CCL5, CD3G,IL7R, PLAC8) were over-presented, as well as two others,CX3CR1, RORA, corresponding to macrophage migration. 31708105 chr5 136274432 136276432 Cux1 Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b mouse connective High+Lowthroughput Cux2 expression regulated by Lhx2 in the upper layer neurons of the developing cortex 否 autism immune cell E_02_0128 PCR, flow cytometry, immunofluorescence staining Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b Immunohistochemical staining Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b PCR,Flow cytometry,免疫荧光染色 Cux1,Cux2,Xlr3b Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b;Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b;Cux1 and Cux2, which are specifically expressed in cortical layer II-IV, have been shown to be involved in synapse formation, dendritic branching, and spine development by directly controlling the expression of Xlr3b and Xlr4b 31707045 chr16 56295383 56297383 Abi3bp Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1). mouse connective High+Lowthroughput TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression 否 cancer cancer cell E_02_0129 PCR, flow cytometry, immunofluorescence staining Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1). Immunohistochemical staining Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1). PCR,Flow cytometry,免疫荧光染色 Abi3bp,Cilp,Pcolce2,Fmod,Aspn,Fn1,Tnxb,Fbln1 Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1).;Consistent with our histological and FTIR analyses, a number of downregulated extracellular matrix genes in the AF corresponded to collagen assembly and organization. These genes included ABI family member 3 binding protein (Abi3bp), cartilage intermediate layer protein (Cilp, Cilp2), procollagen c-endopeptidase enhancer 2 (Pcolce2), fibromodulin (Fmod), asporin (Aspn), fibronectin 1 (Fn1), tenascin X (Tnxb), and fibulin 1 (Fbln1). 31706027 chr16 67559869 67561869 CTCF A popular model explaining loop formation in vertebrates has proposed that the cohesin complex can dynamically bind to DNA and move along the DNA strand, extruding chromatin to form loops until complex movement is stopped by CTCF [14] human High+Lowthroughput Small Drosophila zinc finger C2H2 protein with an N-terminal zinc finger-associated domain demonstrates the architecture functions 否 S2 cell E_02_0130 PCR, flow cytometry, immunofluorescence staining A popular model explaining loop formation in vertebrates has proposed that the cohesin complex can dynamically bind to DNA and move along the DNA strand, extruding chromatin to form loops until complex movement is stopped by CTCF [14] Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A popular model explaining loop formation in vertebrates has proposed that the cohesin complex can dynamically bind to DNA and move along the DNA strand, extruding chromatin to form loops until complex movement is stopped by CTCF [14] Immunohistochemical staining A popular model explaining loop formation in vertebrates has proposed that the cohesin complex can dynamically bind to DNA and move along the DNA strand, extruding chromatin to form loops until complex movement is stopped by CTCF [14] PCR,Flow cytometry,免疫荧光染色 CTCF A popular model explaining loop formation in vertebrates has proposed that the cohesin complex can dynamically bind to DNA and move along the DNA strand, extruding chromatin to form loops until complex movement is stopped by CTCF [14] 31705954 chr3 115620608 115622608 GAP43 The aim of the present study was to evaluate the effect of fluoxetine, a widely used SSRI antidepressant, on the neurogenesis and the expression of Growth-Associated Protein 43 (GAP43), a synaptic protein, in the rat hippocampus exposed to Unpredictable Chronic Mild Stress human Nervous High+Lowthroughput Fluoxetine attenuates stress-induced depressive-like behavior through modulation of hippocampal GAP43 and neurogenesis in male rats 否 depression neural progenitor cell E_02_0131 PCR, immunofluorescence staining The aim of the present study was to evaluate the effect of fluoxetine, a widely used SSRI antidepressant, on the neurogenesis and the expression of Growth-Associated Protein 43 (GAP43), a synaptic protein, in the rat hippocampus exposed to Unpredictable Chronic Mild Stress Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The aim of the present study was to evaluate the effect of fluoxetine, a widely used SSRI antidepressant, on the neurogenesis and the expression of Growth-Associated Protein 43 (GAP43), a synaptic protein, in the rat hippocampus exposed to Unpredictable Chronic Mild Stress Immunohistochemical staining The aim of the present study was to evaluate the effect of fluoxetine, a widely used SSRI antidepressant, on the neurogenesis and the expression of Growth-Associated Protein 43 (GAP43), a synaptic protein, in the rat hippocampus exposed to Unpredictable Chronic Mild Stress PCR,免疫荧光染色 GAP43 The aim of the present study was to evaluate the effect of fluoxetine, a widely used SSRI antidepressant, on the neurogenesis and the expression of Growth-Associated Protein 43 (GAP43), a synaptic protein, in the rat hippocampus exposed to Unpredictable Chronic Mild Stress 31704972 chr12 55964033 55966033 CDK2 Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). human High+Lowthroughput CDK2-mediated site-specific phosphorylation of EZH2 drives and maintains triple-negative breast cancer 否 mammary cancer Triple-negative breast cancer cell E_02_0132 PCR,Western blot Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). Immunohistochemical staining Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). PCR,Western blot CDK2,EZH2 Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2).;Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). 31699991 chr17 42697602 42699602 EZH1 Here we report that AML1-ETO-positive patients, with high histone lysine methyl_x0002_transferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. human connective High+Lowthroughput Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia 否 cancer stem cell E_02_0133 PCR,Western blot Here we report that AML1-ETO-positive patients, with high histone lysine methyl_x0002_transferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we report that AML1-ETO-positive patients, with high histone lysine methyl_x0002_transferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. Immunohistochemical staining Here we report that AML1-ETO-positive patients, with high histone lysine methyl_x0002_transferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. PCR,Western blot EZH1 Here we report that AML1-ETO-positive patients, with high histone lysine methyl_x0002_transferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. 31698854 chrX 25000875 25002875 ARX In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. human connective High+Lowthroughput Changes in Calcium Homeostasis and Gene Expression Implicated in Epilepsy in Hippocampi of Mice Overexpressing ORAI1 否 epilepsy T cell E_02_0134 PCR In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. Immunohistochemical staining In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. PCR ARX,ORAI1,Cdkl5,Dclk1 In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. ;In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. ;In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. ;In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes. 31697837 chr5 88714150 88716150 MEF2C In this context, SIK3maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), arepressive cofactor of MEF2C. human connective High+Lowthroughput Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo 否 Acute myeloid leukemia mutant lymphoma cell E_02_0135 PCR,Flow cytometry,Western blot In this context, SIK3maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), arepressive cofactor of MEF2C. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this context, SIK3maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), arepressive cofactor of MEF2C. Immunohistochemical staining In this context, SIK3maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), arepressive cofactor of MEF2C. PCR,Flow cytometry,Western blot MEF2C In this context, SIK3maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), arepressive cofactor of MEF2C. 31695501 chr7 148804320 148806320 EZH2 Enhancer of zeste 2 homolog (EZH2) is the catalytic subunit of the polycomb repressive complex 2, which is a complex that methylates lysine 27 of histone H3 (H3K27)to repress its gene expression. human connective High+Lowthroughput Silencing Of hsa_circ_0008450 Represses Hepatocellular Carcinoma Progression Through Regulation Of microRNA-214-3p/EZH2 Axis 否 liver cancer cancer cell E_02_0136 PCR,Western blot Enhancer of zeste 2 homolog (EZH2) is the catalytic subunit of the polycomb repressive complex 2, which is a complex that methylates lysine 27 of histone H3 (H3K27)to repress its gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste 2 homolog (EZH2) is the catalytic subunit of the polycomb repressive complex 2, which is a complex that methylates lysine 27 of histone H3 (H3K27)to repress its gene expression. Immunohistochemical staining Enhancer of zeste 2 homolog (EZH2) is the catalytic subunit of the polycomb repressive complex 2, which is a complex that methylates lysine 27 of histone H3 (H3K27)to repress its gene expression. PCR,Western blot EZH2 Enhancer of zeste 2 homolog (EZH2) is the catalytic subunit of the polycomb repressive complex 2, which is a complex that methylates lysine 27 of histone H3 (H3K27)to repress its gene expression. 31695196 chr17 40016366 40018366 MED24 ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. human connective High+Lowthroughput Silencing Of hsa_circ_0008450 Represses Hepatocellular Carcinoma Progression Through Regulation Of microRNA-214-3p/EZH2 Axis 否 embryonic stem cell E_02_0137 PCR,Flow cytometry ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. Immunohistochemical staining ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. PCR,Flow cytometry MED24 ERK triggers the reversible association and disassociation of RNA polymerase II and associated co-factors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. 31694243 chr4 186066778 186068778 TLR3 Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα),extracellular regulated kinases (ERK), and p38, in an in vitro model. human blood High+Lowthroughput Transcriptome analysis reveals a positive effect of brassinosteroids on the photosynthetic capacity of wucai under low temperature 否 leukemia B cell E_02_0138 PCR,Western blot Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα),extracellular regulated kinases (ERK), and p38, in an in vitro model. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα),extracellular regulated kinases (ERK), and p38, in an in vitro model. Immunohistochemical staining Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα),extracellular regulated kinases (ERK), and p38, in an in vitro model. PCR,Western blot TLR3 Interestingly, the interaction of OAA with IκB kinase α/β (IKKα/β) strongly attenuated the production of certain proteins and inflammatory cytokines in the TLR3 signaling pathway, such as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBα),extracellular regulated kinases (ERK), and p38, in an in vitro model. 31692936 chr4 1868930 1870930 NSD2 NSD2 (also known as WHSC1 and MMSET) was initially found to be deleted in Wolf-Hirschhorn syndrome (WHS) and rearranged with the immunoglobulin locus in 15%~20% multiple Ivyspring International Publisher myeloma (MM) cases [4-5]. Indeed, NSD2 gene,encoding two main isoforms, NSD2-long (1,365 aminoacid) and NSD2-short (647 amino acid), was located at chromosome 4p16.3, which exhibits strong cancerrelevance human kidney High+Lowthroughput Investigating the epi-miRNome: identification of epi-miRNAs using transfection experiments 否 renal cell carcinoma Renal cell E_02_0139 PCR,Western blot,Flow cytometry NSD2 (also known as WHSC1 and MMSET) was initially found to be deleted in Wolf-Hirschhorn syndrome (WHS) and rearranged with the immunoglobulin locus in 15%~20% multiple Ivyspring International Publisher myeloma (MM) cases [4-5]. Indeed, NSD2 gene,encoding two main isoforms, NSD2-long (1,365 aminoacid) and NSD2-short (647 amino acid), was located at chromosome 4p16.3, which exhibits strong cancerrelevance Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NSD2 (also known as WHSC1 and MMSET) was initially found to be deleted in Wolf-Hirschhorn syndrome (WHS) and rearranged with the immunoglobulin locus in 15%~20% multiple Ivyspring International Publisher myeloma (MM) cases [4-5]. Indeed, NSD2 gene,encoding two main isoforms, NSD2-long (1,365 aminoacid) and NSD2-short (647 amino acid), was located at chromosome 4p16.3, which exhibits strong cancerrelevance Immunohistochemical staining NSD2 (also known as WHSC1 and MMSET) was initially found to be deleted in Wolf-Hirschhorn syndrome (WHS) and rearranged with the immunoglobulin locus in 15%~20% multiple Ivyspring International Publisher myeloma (MM) cases [4-5]. Indeed, NSD2 gene,encoding two main isoforms, NSD2-long (1,365 aminoacid) and NSD2-short (647 amino acid), was located at chromosome 4p16.3, which exhibits strong cancerrelevance PCR,Western blot,Flow cytometry NSD2 NSD2 (also known as WHSC1 and MMSET) was initially found to be deleted in Wolf-Hirschhorn syndrome (WHS) and rearranged with the immunoglobulin locus in 15%~20% multiple Ivyspring International Publisher myeloma (MM) cases [4-5]. Indeed, NSD2 gene,encoding two main isoforms, NSD2-long (1,365 aminoacid) and NSD2-short (647 amino acid), was located at chromosome 4p16.3, which exhibits strong cancerrelevance 31692093 chr17 82215342 82217342 SLC16A3 Moreover, we demonstrate for the first time that HIF-1α directly activates an intronic enhancer in SLC16A3 under hypoxic conditions. human intervertebral disc High+Lowthroughput Combining GAL4 GFP enhancer trap with split luciferase to measure spatiotemporal promoter activity in Arabidopsis 否 Chronic intervertebral pain intervertebral disc cells E_02_0140 PCR, Western blot, flow cytometry, immunofluorescence staining Moreover, we demonstrate for the first time that HIF-1α directly activates an intronic enhancer in SLC16A3 under hypoxic conditions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, we demonstrate for the first time that HIF-1α directly activates an intronic enhancer in SLC16A3 under hypoxic conditions. Immunohistochemical staining Moreover, we demonstrate for the first time that HIF-1α directly activates an intronic enhancer in SLC16A3 under hypoxic conditions. PCR,Western blot,Flow cytometry,免疫荧光染色 SLC16A3 Moreover, we demonstrate for the first time that HIF-1α directly activates an intronic enhancer in SLC16A3 under hypoxic conditions. 31692040 chr12 55964023 55966023 CDK2 In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells human bone marrow High+Lowthroughput Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health 否 Myeloid leukemia myeloid leukemia cells E_02_0141 PCR, Western blot, flow cytometry, immunofluorescence staining In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells Immunohistochemical staining In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells PCR,Western blot,Flow cytometry,免疫荧光染色 CDK2,CEBPA In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells;Condi_x0002_tional disruption of CEBPA leads to differentiation block(transition from common myeloid to granulocyte mono_x0002_cyte progenitors), granulopoiesis in particular. 31691800 chr21 39443054 39445054 SH3BGR Hi-C data show that rs2836411 is located in a sub-domain spanning from a region upstream of P3 till the 3_x0002_ end of ERG, which is part of a larger TAD spanning from the 3_x0002_ end of ERG to SH3BGR. human Epithelial High+Lowthroughput Berberine Inhibits Adipogenesis in Porcine Adipocytes via AMP-Activated Protein Kinase-Dependent and -Independent Mechanisms 是 rs2836411 Abdominal aortic aneurysm blood vessel endothelial cell E_02_0142 PCR,Flow cytometry Hi-C data show that rs2836411 is located in a sub-domain spanning from a region upstream of P3 till the 3_x0002_ end of ERG, which is part of a larger TAD spanning from the 3_x0002_ end of ERG to SH3BGR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hi-C data show that rs2836411 is located in a sub-domain spanning from a region upstream of P3 till the 3_x0002_ end of ERG, which is part of a larger TAD spanning from the 3_x0002_ end of ERG to SH3BGR. Immunohistochemical staining Hi-C data show that rs2836411 is located in a sub-domain spanning from a region upstream of P3 till the 3_x0002_ end of ERG, which is part of a larger TAD spanning from the 3_x0002_ end of ERG to SH3BGR. PCR,Flow cytometry SH3BGR Hi-C data show that rs2836411 is located in a sub-domain spanning from a region upstream of P3 till the 3_x0002_ end of ERG, which is part of a larger TAD spanning from the 3_x0002_ end of ERG to SH3BGR. 31689455 chr7 100717697 100719697 EPO EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs. human Musculature High+Lowthroughput Erythropoietin attenuates vascular calcification by inhibiting endoplasmic reticulum stress in rats with chronic kidney disease 否 Vascular calcification smooth muscle cell E_02_0143 Western blot,PCR EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs. Immunohistochemical staining EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs. Western blot,PCR EPO,EPOR EPO prevented the reduction of VSMC phenotypic markers, and reversed the increased calcium content and calcium salt deposition in the aortas of CKD rats and cultured calcified VSMCs.;The EPO receptor (EPOR) mediates the pleiotropic effects of EPO in target cells 31686316 chr22 39516753 39518753 ATF4 We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR. human connective High+Lowthroughput CCAAT/enhancer-binding protein beta (C/EBPβ) knockdown reduces inflammation, ER stress, and apoptosis, and promotes autophagy in oxLDL-treated RAW264.7 macrophage cells 否 atherosclerosis macrophage derived foam cell E_02_0144 Western blot,PCR We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR. Immunohistochemical staining We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR. Western blot,PCR ATF4,ATF6,ATG5 We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR.;We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR.;We measured key genes CHOP, mTORC1, genes implicated in ERS [activat_x0002_ing transcription factor 4 & 6 (ATF4, ATF6)] and apopto_x0002_sis (caspase 1, caspase-3 and caspase 12), and autophagy (ATG5, LC3A, LC3B) in macrophage cells by qPCR. 31686214 chr16 86507862 86509862 FOXF1 Haploinsufciency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. human Epithelial High+Lowthroughput Association of rare non-coding SNVs in the lung-specific FOXF1 enhancer with a mitigation of the lethal ACDMPV phenotype 是 rs150502618 Misalignment of pulmonary veins epithelial cell E_02_0145 Flow cytometry,PCR Haploinsufciency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Haploinsufciency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. Immunohistochemical staining Haploinsufciency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. Flow cytometry,PCR FOXF1,CTCF Haploinsufciency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype.;Sequencing of these alleles revealed two rare SNVs, rs150502618-A and rs79301423-T, mapping to the partially overlapping binding sites for TFAP2s and CTCF in the core region of the enhancer. 31684161 chr4 153681439 153683439 TLR2 The qRT-PCR results show that TLR2 transcription was significantly upregulated in RAW264.7 cells stimulated by HP1717, but TLR4 transcription did not significantly change (Figure 4A). human blood High+Lowthroughput HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule 否 inflammation B cell E_02_0146 Western blot,PCR The qRT-PCR results show that TLR2 transcription was significantly upregulated in RAW264.7 cells stimulated by HP1717, but TLR4 transcription did not significantly change (Figure 4A). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The qRT-PCR results show that TLR2 transcription was significantly upregulated in RAW264.7 cells stimulated by HP1717, but TLR4 transcription did not significantly change (Figure 4A). Immunohistochemical staining The qRT-PCR results show that TLR2 transcription was significantly upregulated in RAW264.7 cells stimulated by HP1717, but TLR4 transcription did not significantly change (Figure 4A). Western blot,PCR TLR2,TLR4 The qRT-PCR results show that TLR2 transcription was significantly upregulated in RAW264.7 cells stimulated by HP1717, but TLR4 transcription did not significantly change (Figure 4A). ;The qRT-PCR results show that TLR2 transcription was significantly upregulated in RAW264.7 cells stimulated by HP1717, but TLR4 transcription did not significantly change (Figure 4A). 31681405 chr14 100235887 100237887 YY1 The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. human High+Lowthroughput Enhancer LncRNAs Influence Chromatin Interactions in Different Ways 是 GM12878 cell E_02_0147 Flow cytometry The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. Immunohistochemical staining The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. Flow cytometry YY1 The promoters interacting with elncRNA-associated enhancers were rich in RNA polymerase II and YY1 transcription factor binding sites. We clustered enhancer–promoter pairs into different groups to reflect the different ways in which elncRNAs could influence enhancer–promoter pairs. 31681009 chr8 19899234 19901234 LPL For instance, lipoprotein lipase (LPL) reveals lipid storage in the early stages of differentiation, whereas fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and glycerol-3-phosphate dehydrogenase (G-3-PDH) are involved in triglyceride metabolism in late stages human connective High+Lowthroughput Ghrelin Promotes Proliferation and Inhibits Differentiation of 3T3-L1 and Human Primary Preadipocytes 否 pluripotent stem cell E_02_0148 Western blot,PCR For instance, lipoprotein lipase (LPL) reveals lipid storage in the early stages of differentiation, whereas fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and glycerol-3-phosphate dehydrogenase (G-3-PDH) are involved in triglyceride metabolism in late stages Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For instance, lipoprotein lipase (LPL) reveals lipid storage in the early stages of differentiation, whereas fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and glycerol-3-phosphate dehydrogenase (G-3-PDH) are involved in triglyceride metabolism in late stages Immunohistochemical staining For instance, lipoprotein lipase (LPL) reveals lipid storage in the early stages of differentiation, whereas fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and glycerol-3-phosphate dehydrogenase (G-3-PDH) are involved in triglyceride metabolism in late stages Western blot,PCR LPL For instance, lipoprotein lipase (LPL) reveals lipid storage in the early stages of differentiation, whereas fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and glycerol-3-phosphate dehydrogenase (G-3-PDH) are involved in triglyceride metabolism in late stages 31679819 chr12 48826675 48828675 DDX23 Even when formed, R-loops may be removed either by RNase H1 ac_x0002_tivity that selectively degrades RNA hybridized to DNA (Cerritelli and Crouch, 2009) or alternatively by various helicases such as Senataxin (SETX; Skourti-Stathaki et al., 2011), Aquarius (Sollier et al., 2014), DDX23 (Sridhara et al., 2017), and DHX9 (Cristini et al., 2018), which have all been shown to restrict R-loop accu_x0002_mulation. human uterus High+Lowthroughput R-Loops Promote Antisense Transcription across the Mammalian Genome 否 HeLa cell E_02_0149 Western blot,PCR,Flow cytometry Even when formed, R-loops may be removed either by RNase H1 ac_x0002_tivity that selectively degrades RNA hybridized to DNA (Cerritelli and Crouch, 2009) or alternatively by various helicases such as Senataxin (SETX; Skourti-Stathaki et al., 2011), Aquarius (Sollier et al., 2014), DDX23 (Sridhara et al., 2017), and DHX9 (Cristini et al., 2018), which have all been shown to restrict R-loop accu_x0002_mulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Even when formed, R-loops may be removed either by RNase H1 ac_x0002_tivity that selectively degrades RNA hybridized to DNA (Cerritelli and Crouch, 2009) or alternatively by various helicases such as Senataxin (SETX; Skourti-Stathaki et al., 2011), Aquarius (Sollier et al., 2014), DDX23 (Sridhara et al., 2017), and DHX9 (Cristini et al., 2018), which have all been shown to restrict R-loop accu_x0002_mulation. Immunohistochemical staining Even when formed, R-loops may be removed either by RNase H1 ac_x0002_tivity that selectively degrades RNA hybridized to DNA (Cerritelli and Crouch, 2009) or alternatively by various helicases such as Senataxin (SETX; Skourti-Stathaki et al., 2011), Aquarius (Sollier et al., 2014), DDX23 (Sridhara et al., 2017), and DHX9 (Cristini et al., 2018), which have all been shown to restrict R-loop accu_x0002_mulation. Western blot,PCR,Flow cytometry DDX23,ZEB2 Even when formed, R-loops may be removed either by RNase H1 ac_x0002_tivity that selectively degrades RNA hybridized to DNA (Cerritelli and Crouch, 2009) or alternatively by various helicases such as Senataxin (SETX; Skourti-Stathaki et al., 2011), Aquarius (Sollier et al., 2014), DDX23 (Sridhara et al., 2017), and DHX9 (Cristini et al., 2018), which have all been shown to restrict R-loop accu_x0002_mulation.;Similarly, the ZEB2 gene, which is associated with stem celldevelopment and reprogramming, generates a lncRNA (referred to as a native AS RNA or NAT) initiating in the ZEB2 intron 1 that plays a positive role in activating ZEB2 expression. 31678303 chr1 156461181 156463181 MEF2D MEF2D protein acetylation and proteins that interact with MEF2D were identified by co-immunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls) were transplanted into BALB/c mice, some mice were given antibodies to deplete T cells. human liver High+Lowthroughput Disruption of SIRT7 Increases the Efficacy of Checkpoint Inhibitor via MEF2D Regulation of Programmed Cell Death 1 Ligand 1 in Hepatocellular Carcinoma Cells 否 liver cancer hepatocellular carcinoma cell E_02_0150 Western blot, PCR, flow cytometry, immunofluorescence staining MEF2D protein acetylation and proteins that interact with MEF2D were identified by co-immunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls) were transplanted into BALB/c mice, some mice were given antibodies to deplete T cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2D protein acetylation and proteins that interact with MEF2D were identified by co-immunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls) were transplanted into BALB/c mice, some mice were given antibodies to deplete T cells. Immunohistochemical staining MEF2D protein acetylation and proteins that interact with MEF2D were identified by co-immunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls) were transplanted into BALB/c mice, some mice were given antibodies to deplete T cells. Western blot,PCR,Flow cytometry,免疫荧光染色 MEF2D,SIRT7,CD274 MEF2D protein acetylation and proteins that interact with MEF2D were identified by co-immunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls) were transplanted into BALB/c mice, some mice were given antibodies to deplete T cells. ;Mice bearing orthotopic tumors grown from HCC cells with or without knockout of SIRT7, were given injections of an antibody against PD1.;MEF2D bound the promoter region of the CD274 gene (encodes PD-L1) and activated its transcription. 31676828 chr1 92469783 92471783 GFI1 In erythro–megakaryocyte lineage leukemia cells, activation of the SE of GFI1 (GFI1-SE) is related to induction of myeloid differentiation by LSD1 inhibitors NCD38 and NCD25 and to their antileukemia effect. human blood High+Lowthroughput LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia 否 leukemia leukemic cell E_02_0151 Flow cytometry,PCR In erythro–megakaryocyte lineage leukemia cells, activation of the SE of GFI1 (GFI1-SE) is related to induction of myeloid differentiation by LSD1 inhibitors NCD38 and NCD25 and to their antileukemia effect. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In erythro–megakaryocyte lineage leukemia cells, activation of the SE of GFI1 (GFI1-SE) is related to induction of myeloid differentiation by LSD1 inhibitors NCD38 and NCD25 and to their antileukemia effect. Immunohistochemical staining In erythro–megakaryocyte lineage leukemia cells, activation of the SE of GFI1 (GFI1-SE) is related to induction of myeloid differentiation by LSD1 inhibitors NCD38 and NCD25 and to their antileukemia effect. Flow cytometry,PCR GFI1 In erythro–megakaryocyte lineage leukemia cells, activation of the SE of GFI1 (GFI1-SE) is related to induction of myeloid differentiation by LSD1 inhibitors NCD38 and NCD25 and to their antileukemia effect. 31676673 chrX 49025404 49027404 TFE3 Our results reveal that Fnip1 coordinates multiple metabolic pathways regulated by AMPK, mTORC1, and transcription factor binding to IgHM enhancer 3 (TFE3) to maintain metabolic ho_x0002_meostasis necessary for pre–B cell survival and differentiation during metabolic stress. human blood High+Lowthroughput Folliculin Interacting Protein 1 Maintains Metabolic Homeostasis during B Cell Development by Modulating AMPK, mTORC1, and TFE3 否 B cell E_02_0152 Flow cytometry,PCR Our results reveal that Fnip1 coordinates multiple metabolic pathways regulated by AMPK, mTORC1, and transcription factor binding to IgHM enhancer 3 (TFE3) to maintain metabolic ho_x0002_meostasis necessary for pre–B cell survival and differentiation during metabolic stress. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results reveal that Fnip1 coordinates multiple metabolic pathways regulated by AMPK, mTORC1, and transcription factor binding to IgHM enhancer 3 (TFE3) to maintain metabolic ho_x0002_meostasis necessary for pre–B cell survival and differentiation during metabolic stress. Immunohistochemical staining Our results reveal that Fnip1 coordinates multiple metabolic pathways regulated by AMPK, mTORC1, and transcription factor binding to IgHM enhancer 3 (TFE3) to maintain metabolic ho_x0002_meostasis necessary for pre–B cell survival and differentiation during metabolic stress. Flow cytometry,PCR TFE3 Our results reveal that Fnip1 coordinates multiple metabolic pathways regulated by AMPK, mTORC1, and transcription factor binding to IgHM enhancer 3 (TFE3) to maintain metabolic ho_x0002_meostasis necessary for pre–B cell survival and differentiation during metabolic stress. 31675590 chr7 148804429 148806429 EZH2 Our results indicate that Cd at1 mM concentration increases the viability of HepG2 and MCF7 cells and significantly upregulates the expression of PRMT5 and EZH2, leading to an increased global level of symmetric dimethylarginine(SDMA), H4R3me2s, and H3K27me3. human connective High+Lowthroughput The carcinogen cadmium elevates CpG-demethylation and enrichment of NFYA and E2F1 in the promoter of oncogenic PRMT5 and EZH2 methyltransferases resulting in their elevated expression in?vitro 否 cancer HepG2 cell E_02_0153 Western blot,PCR,Flow cytometry Our results indicate that Cd at1 mM concentration increases the viability of HepG2 and MCF7 cells and significantly upregulates the expression of PRMT5 and EZH2, leading to an increased global level of symmetric dimethylarginine(SDMA), H4R3me2s, and H3K27me3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results indicate that Cd at1 mM concentration increases the viability of HepG2 and MCF7 cells and significantly upregulates the expression of PRMT5 and EZH2, leading to an increased global level of symmetric dimethylarginine(SDMA), H4R3me2s, and H3K27me3. Immunohistochemical staining Our results indicate that Cd at1 mM concentration increases the viability of HepG2 and MCF7 cells and significantly upregulates the expression of PRMT5 and EZH2, leading to an increased global level of symmetric dimethylarginine(SDMA), H4R3me2s, and H3K27me3. Western blot,PCR,Flow cytometry EZH2 Our results indicate that Cd at1 mM concentration increases the viability of HepG2 and MCF7 cells and significantly upregulates the expression of PRMT5 and EZH2, leading to an increased global level of symmetric dimethylarginine(SDMA), H4R3me2s, and H3K27me3. 31672165 chr17 47197711 47199711 MYL4 Interestingly, while HEK293 cells are not thought to express MYL4, human MYL4 is known to be slightly larger than the mouse protein. human blood High+Lowthroughput Contaminating reactivity of a monoclonal CCAAT/Enhancer Binding Protein β antibody in differentiating myoblasts 否 B cell E_02_0154 Western blot Interestingly, while HEK293 cells are not thought to express MYL4, human MYL4 is known to be slightly larger than the mouse protein. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Interestingly, while HEK293 cells are not thought to express MYL4, human MYL4 is known to be slightly larger than the mouse protein. Immunohistochemical staining Interestingly, while HEK293 cells are not thought to express MYL4, human MYL4 is known to be slightly larger than the mouse protein. Western blot MYL4 Interestingly, while HEK293 cells are not thought to express MYL4, human MYL4 is known to be slightly larger than the mouse protein. 31668620 chr13 118804154 118806154 Fgf10 Analyzing open chromatin revealsdifferentially active regulatory elements near Fgf10 and Sall-1 in the emu wing, and the Sall-1 enhancer ac_x0002_tivity is dependent on a likely Fgf-mediated Ets tran_x0002_scription factor-binding site. mouse Musculature High+Lowthroughput Attenuated Fgf Signaling Underlies the Forelimb Heterochrony in the Emu Dromaius novaehollandiae 否 muscle cell E_02_0155 Flow cytometry, PCR, immunofluorescence staining Analyzing open chromatin revealsdifferentially active regulatory elements near Fgf10 and Sall-1 in the emu wing, and the Sall-1 enhancer ac_x0002_tivity is dependent on a likely Fgf-mediated Ets tran_x0002_scription factor-binding site. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Analyzing open chromatin revealsdifferentially active regulatory elements near Fgf10 and Sall-1 in the emu wing, and the Sall-1 enhancer ac_x0002_tivity is dependent on a likely Fgf-mediated Ets tran_x0002_scription factor-binding site. Immunohistochemical staining Analyzing open chromatin revealsdifferentially active regulatory elements near Fgf10 and Sall-1 in the emu wing, and the Sall-1 enhancer ac_x0002_tivity is dependent on a likely Fgf-mediated Ets tran_x0002_scription factor-binding site. Flow cytometry,PCR,免疫荧光染色 Fgf10 Analyzing open chromatin revealsdifferentially active regulatory elements near Fgf10 and Sall-1 in the emu wing, and the Sall-1 enhancer ac_x0002_tivity is dependent on a likely Fgf-mediated Ets tran_x0002_scription factor-binding site. 31666665 chr7 148804251 148806251 EZH2 Enhancer of zester homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PCR2), and its-terminal SET domain exhibits methyl transferase activity9 human lung High+Lowthroughput Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients 否 lung cancer Lung cancer cell E_02_0156 PCR, Western blot, immunofluorescence staining Enhancer of zester homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PCR2), and its-terminal SET domain exhibits methyl transferase activity9 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zester homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PCR2), and its-terminal SET domain exhibits methyl transferase activity9 Immunohistochemical staining Enhancer of zester homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PCR2), and its-terminal SET domain exhibits methyl transferase activity9 PCR,Western blot,免疫荧光染色 EZH2 Enhancer of zester homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PCR2), and its-terminal SET domain exhibits methyl transferase activity9 31666509 chr3 38545360 38547360 SCN5A Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia dis_x0002_orders. human heart High+Lowthroughput An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo 是 rs6810361 Arrhythmia cardiac muscle cell (sensu Arthopoda) E_02_0157 Flow cytometry,PCR Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia dis_x0002_orders. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia dis_x0002_orders. Immunohistochemical staining Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia dis_x0002_orders. Flow cytometry,PCR SCN5A,SCN10A Mutations and variations in and around SCN5A, encoding the major cardiac sodium channel, influence impulse conduction and are associated with a broad spectrum of arrhythmia dis_x0002_orders.;The activity of REs is largely limited to target genes that fall within the same TAD8, including SCN5A, SCN10A, EXOG, SCN11A, and WDR48. 31665646 chrX 73818246 73820246 XIST HEK293 are female cells and, therefore, one of the two X chromosomes is subject to X chromosome inactivation, a process that is dependent on the expression of the XIST lncRNA (da Rocha and Heard, 2017; Jégu et al., 2017). Both MapR and RHΔC&R signals are clearly higher than the respective controls at the 5′ end of the XIST gene (Figure 2E). human connective High+Lowthroughput Mapping Native R-Loops Genome-wide Using a Targeted Nuclease Approach 否 cancer HEK293 cell E_02_0158 Flow cytometry,PCR HEK293 are female cells and, therefore, one of the two X chromosomes is subject to X chromosome inactivation, a process that is dependent on the expression of the XIST lncRNA (da Rocha and Heard, 2017; Jégu et al., 2017). Both MapR and RHΔC&R signals are clearly higher than the respective controls at the 5′ end of the XIST gene (Figure 2E). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HEK293 are female cells and, therefore, one of the two X chromosomes is subject to X chromosome inactivation, a process that is dependent on the expression of the XIST lncRNA (da Rocha and Heard, 2017; Jégu et al., 2017). Both MapR and RHΔC&R signals are clearly higher than the respective controls at the 5′ end of the XIST gene (Figure 2E). Immunohistochemical staining HEK293 are female cells and, therefore, one of the two X chromosomes is subject to X chromosome inactivation, a process that is dependent on the expression of the XIST lncRNA (da Rocha and Heard, 2017; Jégu et al., 2017). Both MapR and RHΔC&R signals are clearly higher than the respective controls at the 5′ end of the XIST gene (Figure 2E). Flow cytometry,PCR XIST HEK293 are female cells and, therefore, one of the two X chromosomes is subject to X chromosome inactivation, a process that is dependent on the expression of the XIST lncRNA (da Rocha and Heard, 2017; Jégu et al., 2017). Both MapR and RHΔC&R signals are clearly higher than the respective controls at the 5′ end of the XIST gene (Figure 2E). 31665330 chr16 68733997 68735997 CDH1 On the other hand, numerous epithelial cell markers including CDH1, CLDN1, CLDN4, CLDN8, CLDN10, KLF4 and KLF5 were all upregulated during MS. human Epithelial High+Lowthroughput Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators 否 Infertility epithelial cell E_02_0159 PCR On the other hand, numerous epithelial cell markers including CDH1, CLDN1, CLDN4, CLDN8, CLDN10, KLF4 and KLF5 were all upregulated during MS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq On the other hand, numerous epithelial cell markers including CDH1, CLDN1, CLDN4, CLDN8, CLDN10, KLF4 and KLF5 were all upregulated during MS. Immunohistochemical staining On the other hand, numerous epithelial cell markers including CDH1, CLDN1, CLDN4, CLDN8, CLDN10, KLF4 and KLF5 were all upregulated during MS. PCR CDH1,KLF5 On the other hand, numerous epithelial cell markers including CDH1, CLDN1, CLDN4, CLDN8, CLDN10, KLF4 and KLF5 were all upregulated during MS. ;On the other hand, numerous epithelial cell markers including CDH1, CLDN1, CLDN4, CLDN8, CLDN10, KLF4 and KLF5 were all upregulated during MS. 31665135 chr8 116842944 116844944 RAD21 Similarly, CTCF, RAD21, and H3K4me3 occurred more often at interacting pro_x0002_moters than non-interacting promoters (Fig 7). Taken together, histone marks and relevant factors suggested that our prediction of enhancer-target relationships were likely biologically functional. human blood High+Lowthroughput EAGLE: An algorithm that utilizes a small number of genomic features to predict tissue/cell type-specific enhancer-gene interactions 否 E_02_0160 Flow cytometry,PCR Similarly, CTCF, RAD21, and H3K4me3 occurred more often at interacting pro_x0002_moters than non-interacting promoters (Fig 7). Taken together, histone marks and relevant factors suggested that our prediction of enhancer-target relationships were likely biologically functional. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Similarly, CTCF, RAD21, and H3K4me3 occurred more often at interacting pro_x0002_moters than non-interacting promoters (Fig 7). Taken together, histone marks and relevant factors suggested that our prediction of enhancer-target relationships were likely biologically functional. Immunohistochemical staining Similarly, CTCF, RAD21, and H3K4me3 occurred more often at interacting pro_x0002_moters than non-interacting promoters (Fig 7). Taken together, histone marks and relevant factors suggested that our prediction of enhancer-target relationships were likely biologically functional. Flow cytometry,PCR RAD21,CTCF Similarly, CTCF, RAD21, and H3K4me3 occurred more often at interacting pro_x0002_moters than non-interacting promoters (Fig 7). Taken together, histone marks and relevant factors suggested that our prediction of enhancer-target relationships were likely biologically functional.;Similarly, CTCF, RAD21, and H3K4me3 occurred more often at interacting pro_x0002_moters than non-interacting promoters (Fig 7). Taken together, histone marks and relevant factors suggested that our prediction of enhancer-target relationships were likely biologically functional. 31662342 chr16 86508235 86510235 FOXF1 Tran_x0002_scriptional profiling of lung samples obtained from normal human fetal lung tissues ranging from 53 to 140 days of gesta_x0002_tion demonstrated that FOXF1 has robust, stable expression throughout early human lung development (online supplemen_x0002_tary figure 4,11). human Epithelial High+Lowthroughput Disruption of normal patterns of FOXF1 expression in a lethal disorder of lung development 否 cancer endothelial cell E_02_0161 Flow cytometry,PCR,Western blot Tran_x0002_scriptional profiling of lung samples obtained from normal human fetal lung tissues ranging from 53 to 140 days of gesta_x0002_tion demonstrated that FOXF1 has robust, stable expression throughout early human lung development (online supplemen_x0002_tary figure 4,11). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Tran_x0002_scriptional profiling of lung samples obtained from normal human fetal lung tissues ranging from 53 to 140 days of gesta_x0002_tion demonstrated that FOXF1 has robust, stable expression throughout early human lung development (online supplemen_x0002_tary figure 4,11). Immunohistochemical staining Tran_x0002_scriptional profiling of lung samples obtained from normal human fetal lung tissues ranging from 53 to 140 days of gesta_x0002_tion demonstrated that FOXF1 has robust, stable expression throughout early human lung development (online supplemen_x0002_tary figure 4,11). Flow cytometry,PCR,Western blot FOXF1 Tran_x0002_scriptional profiling of lung samples obtained from normal human fetal lung tissues ranging from 53 to 140 days of gesta_x0002_tion demonstrated that FOXF1 has robust, stable expression throughout early human lung development (online supplemen_x0002_tary figure 4,11). 31661141 chr12 2855382 2857382 FOXM1 In this study, we report that E2F-1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A). human uterus High+Lowthroughput Crosstalk between histone modification and DNA methylation orchestrates the epigenetic regulation of the costimulatory factors, Tim?3 and galectin?9, in cervical cancer 否 cervical carcinoma HeLa cell E_02_0162 PCR,Western blot In this study, we report that E2F-1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we report that E2F-1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A). Immunohistochemical staining In this study, we report that E2F-1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A). PCR,Western blot FOXM1,EZH2 In this study, we report that E2F-1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A).;In this study, we report that E2F-1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2‑specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A). 31661121 chr17 58267209 58269209 MPO Measurement of myeloperoxidase (MPO), malondialde‑hyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels. The MPO, MDA, SOD and GSH levels were detected using the related kits (MPO: cat. no. A044; MDA: cat. no. A003; SOD: cat. no. A001; GSH: cat. no. A005; Nanjing Jiancheng Bioengineering Institute). human Epithelial High+Lowthroughput Dihydroartemisinin attenuates lipopolysaccharide?induced acute lung injury in mice by suppressing NF?κB signaling in an Nrf2?dependent manner 否 inflammation epithelial cell E_02_0163 PCR, Western blot, immunofluorescence staining Measurement of myeloperoxidase (MPO), malondialde‑hyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels. The MPO, MDA, SOD and GSH levels were detected using the related kits (MPO: cat. no. A044; MDA: cat. no. A003; SOD: cat. no. A001; GSH: cat. no. A005; Nanjing Jiancheng Bioengineering Institute). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Measurement of myeloperoxidase (MPO), malondialde‑hyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels. The MPO, MDA, SOD and GSH levels were detected using the related kits (MPO: cat. no. A044; MDA: cat. no. A003; SOD: cat. no. A001; GSH: cat. no. A005; Nanjing Jiancheng Bioengineering Institute). Immunohistochemical staining Measurement of myeloperoxidase (MPO), malondialde‑hyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels. The MPO, MDA, SOD and GSH levels were detected using the related kits (MPO: cat. no. A044; MDA: cat. no. A003; SOD: cat. no. A001; GSH: cat. no. A005; Nanjing Jiancheng Bioengineering Institute). PCR,Western blot,免疫荧光染色 MPO Measurement of myeloperoxidase (MPO), malondialde‑hyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels. The MPO, MDA, SOD and GSH levels were detected using the related kits (MPO: cat. no. A044; MDA: cat. no. A003; SOD: cat. no. A001; GSH: cat. no. A005; Nanjing Jiancheng Bioengineering Institute). 31659118 chr7 97849158 97851158 ASNS Insufficient expression of ASNS leads to asparagine deficiency, which facilitates an ATF4-independent induction of C/EBP homologous protein (CHOP) that triggers apoptosis. human tumour High+Lowthroughput Promoter demethylation of the asparagine synthetase gene is required for ATF4-dependent adaptation to asparagine depletion 否 acute lymphoblastic leukemia tumor cell E_02_0164 Flow cytometry,Western blot,PCR Insufficient expression of ASNS leads to asparagine deficiency, which facilitates an ATF4-independent induction of C/EBP homologous protein (CHOP) that triggers apoptosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Insufficient expression of ASNS leads to asparagine deficiency, which facilitates an ATF4-independent induction of C/EBP homologous protein (CHOP) that triggers apoptosis. Immunohistochemical staining Insufficient expression of ASNS leads to asparagine deficiency, which facilitates an ATF4-independent induction of C/EBP homologous protein (CHOP) that triggers apoptosis. Flow cytometry,Western blot,PCR ASNS,SESN2 Insufficient expression of ASNS leads to asparagine deficiency, which facilitates an ATF4-independent induction of C/EBP homologous protein (CHOP) that triggers apoptosis. ;As a control, there was induced recruitment of ATF4 to the promoter region of another target gene, SESN2 (Figure 3E), following asparagine depletion in both the RS4;11 and RS4;11/R cells (Figure 4G, right). 31658410 chr14 48891897 48893897 Otx2 Homeodomain transcription factor Otx2 is essential for embryonic development of multiple head tissues, including retinal pigment epithelium (RPE) and neuroretina. Temporospatial regulation of Otx2 expression is critical for its functions. mouse connective High+Lowthroughput A distal enhancer that directs Otx2 expression in the retinal pigment epithelium and neuroretina 否 pluripotent stem cell E_02_0165 Flow cytometry, immunofluorescence staining Homeodomain transcription factor Otx2 is essential for embryonic development of multiple head tissues, including retinal pigment epithelium (RPE) and neuroretina. Temporospatial regulation of Otx2 expression is critical for its functions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Homeodomain transcription factor Otx2 is essential for embryonic development of multiple head tissues, including retinal pigment epithelium (RPE) and neuroretina. Temporospatial regulation of Otx2 expression is critical for its functions. Immunohistochemical staining Homeodomain transcription factor Otx2 is essential for embryonic development of multiple head tissues, including retinal pigment epithelium (RPE) and neuroretina. Temporospatial regulation of Otx2 expression is critical for its functions. Flow cytometry，免疫荧光染色 Otx2,PAX6 Homeodomain transcription factor Otx2 is essential for embryonic development of multiple head tissues, including retinal pigment epithelium (RPE) and neuroretina. Temporospatial regulation of Otx2 expression is critical for its functions.;In the 392-bp mouse hs1150 element, recognition sites for transcription factors PAX6, CHX10, CRX, BLIMP1, and OTX were found (Fig. 6A, B), suggesting that hs1150 enhancer could be regulated by these transcription factors thatare essential for neuroretinal cell differentiation 31657619 chr1 26690155 26692155 ARID1A For example, previous studies have identified several key genetic alterations that are linked to gastric malignancy, including mutations in the chromatin modifier gene AT-rich interaction domain 1A (ARID1A) and amplifications in human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), and mesenchymal–epithelial transition (MET) human connective High+Lowthroughput Altered 5-Hydroxymethylcytosine Landscape in Primary Gastric Adenocarcinoma 否 gastric cancer embryonic stem cell E_02_0166 PCR For example, previous studies have identified several key genetic alterations that are linked to gastric malignancy, including mutations in the chromatin modifier gene AT-rich interaction domain 1A (ARID1A) and amplifications in human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), and mesenchymal–epithelial transition (MET) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For example, previous studies have identified several key genetic alterations that are linked to gastric malignancy, including mutations in the chromatin modifier gene AT-rich interaction domain 1A (ARID1A) and amplifications in human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), and mesenchymal–epithelial transition (MET) Immunohistochemical staining For example, previous studies have identified several key genetic alterations that are linked to gastric malignancy, including mutations in the chromatin modifier gene AT-rich interaction domain 1A (ARID1A) and amplifications in human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), and mesenchymal–epithelial transition (MET) PCR ARID1A,FGFR2 For example, previous studies have identified several key genetic alterations that are linked to gastric malignancy, including mutations in the chromatin modifier gene AT-rich interaction domain 1A (ARID1A) and amplifications in human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), and mesenchymal–epithelial transition (MET);For example, previous studies have identified several key genetic alterations that are linked to gastric malignancy, including mutations in the chromatin modifier gene AT-rich interaction domain 1A (ARID1A) and amplifications in human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 2 (FGFR2), and mesenchymal–epithelial transition (MET) 31654083 chr17 44073800 44075800 HDAC5 HDAC5 is recruited to its target genesthrough interactions with transcription factors, i.e., myocyte en_x0002_hancer factor 2 (MEF2), to repress target gene transcription (Parra and Verdin 2010). human blood High+Lowthroughput Early-life blockade of NMDA receptors induces epigenetic abnormalities in the adult medial prefrontal cortex: possible involvement in memory impairment in trace fear conditioning 否 Schizophrenia E_02_0167 PCR,Western blot HDAC5 is recruited to its target genesthrough interactions with transcription factors, i.e., myocyte en_x0002_hancer factor 2 (MEF2), to repress target gene transcription (Parra and Verdin 2010). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HDAC5 is recruited to its target genesthrough interactions with transcription factors, i.e., myocyte en_x0002_hancer factor 2 (MEF2), to repress target gene transcription (Parra and Verdin 2010). Immunohistochemical staining HDAC5 is recruited to its target genesthrough interactions with transcription factors, i.e., myocyte en_x0002_hancer factor 2 (MEF2), to repress target gene transcription (Parra and Verdin 2010). PCR,Western blot HDAC5 HDAC5 is recruited to its target genesthrough interactions with transcription factors, i.e., myocyte en_x0002_hancer factor 2 (MEF2), to repress target gene transcription (Parra and Verdin 2010). 31653691 chr12 107873350 107875350 Bcl11b To com_x0002_pare the molecular mechanisms through which Bcl11b controls cell type–specific gene regulation in the two contexts, we first examined the DNA binding patterns of Bcl11b across the genome in pro-T cells with those in ILC2 cells. mouse blood High+Lowthroughput Cell type-specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells 否 mutant lymphoma cell E_02_0168 Flow cytometry,Western blot,PCR To com_x0002_pare the molecular mechanisms through which Bcl11b controls cell type–specific gene regulation in the two contexts, we first examined the DNA binding patterns of Bcl11b across the genome in pro-T cells with those in ILC2 cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To com_x0002_pare the molecular mechanisms through which Bcl11b controls cell type–specific gene regulation in the two contexts, we first examined the DNA binding patterns of Bcl11b across the genome in pro-T cells with those in ILC2 cells. Immunohistochemical staining To com_x0002_pare the molecular mechanisms through which Bcl11b controls cell type–specific gene regulation in the two contexts, we first examined the DNA binding patterns of Bcl11b across the genome in pro-T cells with those in ILC2 cells. Flow cytometry,Western blot,PCR Bcl11b,Runx1,GATA3 To com_x0002_pare the molecular mechanisms through which Bcl11b controls cell type–specific gene regulation in the two contexts, we first examined the DNA binding patterns of Bcl11b across the genome in pro-T cells with those in ILC2 cells.;Thus, globally, Runx1, Runx3, and Bcl11b binding sites across the genome were often coincident within a cell type, but differed markedly between pro-T and ILC2 contexts.;These results show sharp lineagespecific binding differences both for the Runx factors, usually co-recruited with Bcl11b, and for GATA3, often recruited inde pendently of Bcl11b. They also indicate a likely role for a bZIP family member in defining ILC2-specific occupancy sites of Bcl11b, Runx factors, and GATA3 31652979 chr8 127732500 127734500 MYC Gene set enrichment analysis revealed that DKI cells were enriched over single mutant cells for genes that characterize a MYC target gene signature. human breast High+Lowthroughput PIK3CA Cooperates with KRAS to Promote MYC Activity and Tumorigenesis via the Bromodomain Protein BRD9 否 tumour mammary gland epithelial cell E_02_0169 Western blot Gene set enrichment analysis revealed that DKI cells were enriched over single mutant cells for genes that characterize a MYC target gene signature. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Gene set enrichment analysis revealed that DKI cells were enriched over single mutant cells for genes that characterize a MYC target gene signature. Immunohistochemical staining Gene set enrichment analysis revealed that DKI cells were enriched over single mutant cells for genes that characterize a MYC target gene signature. Western blot MYC Gene set enrichment analysis revealed that DKI cells were enriched over single mutant cells for genes that characterize a MYC target gene signature. 31651209 chr2 236162410 236164410 GBX2 A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. human High+Lowthroughput GSK343 induces programmed cell death through the inhibition of EZH2 and FBP1 in osteosarcoma cells 否 Nerve injury Schwann cell E_02_0170 PCR, Western blot, immunofluorescence staining A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. Immunohistochemical staining A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. PCR,Western blot ,免疫荧光染色 GBX2,ZBTB16 A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network.;A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. 31650361 chr2 236162780 236164780 GBX2 A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. - human connective High+Lowthroughput Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype 否 Schwann cell E_02_0171 Western blot, PCR, gene knockdown A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. - Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. - Immunohistochemical staining A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. - Western blot,PCR,基因敲降 GBX2 A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identifed to be commonly diferentially expressed at 1, 4, 7, and 14 days after nerve injury. - 31649847 chr11 70018598 70020598 Mgl2 Kin increased the expression of M2-related genes Mgl1, Mgl2,Pgc1-β, Arg-1, Il-10 and Cd206 (Fig. 3A). mouse connective High+Lowthroughput Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes 否 Osteoarthritis macrophage E_02_0172 PCR, Western blot, flow cytometry, gene knockdown Kin increased the expression of M2-related genes Mgl1, Mgl2,Pgc1-β, Arg-1, Il-10 and Cd206 (Fig. 3A). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Kin increased the expression of M2-related genes Mgl1, Mgl2,Pgc1-β, Arg-1, Il-10 and Cd206 (Fig. 3A). Immunohistochemical staining Kin increased the expression of M2-related genes Mgl1, Mgl2,Pgc1-β, Arg-1, Il-10 and Cd206 (Fig. 3A). PCR,Western blot,Flow cytometry,基因敲降 Mgl2 Kin increased the expression of M2-related genes Mgl1, Mgl2,Pgc1-β, Arg-1, Il-10 and Cd206 (Fig. 3A). 31644911 chr8 101489945 101491945 GRHL2 Motif enrichment analysis of sequences within the ‘‘gained’’ DHSs in TAMR indicated that the transcription factors most likely to be interacting at these genomic loci include those that bind bZip motifs, GRHL2, AP2 factors, ER, and FOXA family members (Figure 1B). human breast High+Lowthroughput The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer 否 mammary cancer breast cancer cell E_02_0173 PCR,Western blot,Flow cytometry Motif enrichment analysis of sequences within the ‘‘gained’’ DHSs in TAMR indicated that the transcription factors most likely to be interacting at these genomic loci include those that bind bZip motifs, GRHL2, AP2 factors, ER, and FOXA family members (Figure 1B). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Motif enrichment analysis of sequences within the ‘‘gained’’ DHSs in TAMR indicated that the transcription factors most likely to be interacting at these genomic loci include those that bind bZip motifs, GRHL2, AP2 factors, ER, and FOXA family members (Figure 1B). Immunohistochemical staining Motif enrichment analysis of sequences within the ‘‘gained’’ DHSs in TAMR indicated that the transcription factors most likely to be interacting at these genomic loci include those that bind bZip motifs, GRHL2, AP2 factors, ER, and FOXA family members (Figure 1B). PCR,Western blot,Flow cytometry GRHL2 Motif enrichment analysis of sequences within the ‘‘gained’’ DHSs in TAMR indicated that the transcription factors most likely to be interacting at these genomic loci include those that bind bZip motifs, GRHL2, AP2 factors, ER, and FOXA family members (Figure 1B). 31632241 chr20 50885804 50887804 ADNP Activity-dependent neuroprotective protein (ADNP) has been initially discovered through its eight amino acid sequence NAPVSIPQ (Bassan et al., 1999), which shares SIP motif with SALLRSIPA – a peptide derived from activity-dependent neurotrophic factor (ADNF) (Brenneman and Gozes, 1996; Zamostiano et al., 1999). human High+Lowthroughput A Novel Microtubule-Tau Association Enhancer and Neuroprotective Drug Candidate: Ac-SKIP 否 Alzheimer E_02_0174 Flow cytometry,PCR,Western blot Activity-dependent neuroprotective protein (ADNP) has been initially discovered through its eight amino acid sequence NAPVSIPQ (Bassan et al., 1999), which shares SIP motif with SALLRSIPA – a peptide derived from activity-dependent neurotrophic factor (ADNF) (Brenneman and Gozes, 1996; Zamostiano et al., 1999). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Activity-dependent neuroprotective protein (ADNP) has been initially discovered through its eight amino acid sequence NAPVSIPQ (Bassan et al., 1999), which shares SIP motif with SALLRSIPA – a peptide derived from activity-dependent neurotrophic factor (ADNF) (Brenneman and Gozes, 1996; Zamostiano et al., 1999). Immunohistochemical staining Activity-dependent neuroprotective protein (ADNP) has been initially discovered through its eight amino acid sequence NAPVSIPQ (Bassan et al., 1999), which shares SIP motif with SALLRSIPA – a peptide derived from activity-dependent neurotrophic factor (ADNF) (Brenneman and Gozes, 1996; Zamostiano et al., 1999). Flow cytometry,PCR,Western blot ADNP Activity-dependent neuroprotective protein (ADNP) has been initially discovered through its eight amino acid sequence NAPVSIPQ (Bassan et al., 1999), which shares SIP motif with SALLRSIPA – a peptide derived from activity-dependent neurotrophic factor (ADNF) (Brenneman and Gozes, 1996; Zamostiano et al., 1999). 31631036 chr7 148804245 148806245 EZH2 To ascertain whether EZH2 expression was correlated with CEP degeneration, immunohistochemical analysis of human CEP tissue was used to compare the level of EZH2 in normal and degenerated human CEP. It was found that the expression of EZH2 increased in degenerated human CEP (Fig. 1D and 1E). human connective High+Lowthroughput Inhibition of EZH2 ameliorates cartilage endplate degeneration and attenuates the progression of intervertebral disc degeneration via demethylation of Sox-9 否 Disc degeneration stem cell E_02_0175 PCR,Western blot To ascertain whether EZH2 expression was correlated with CEP degeneration, immunohistochemical analysis of human CEP tissue was used to compare the level of EZH2 in normal and degenerated human CEP. It was found that the expression of EZH2 increased in degenerated human CEP (Fig. 1D and 1E). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To ascertain whether EZH2 expression was correlated with CEP degeneration, immunohistochemical analysis of human CEP tissue was used to compare the level of EZH2 in normal and degenerated human CEP. It was found that the expression of EZH2 increased in degenerated human CEP (Fig. 1D and 1E). Immunohistochemical staining To ascertain whether EZH2 expression was correlated with CEP degeneration, immunohistochemical analysis of human CEP tissue was used to compare the level of EZH2 in normal and degenerated human CEP. It was found that the expression of EZH2 increased in degenerated human CEP (Fig. 1D and 1E). PCR,Western blot EZH2 To ascertain whether EZH2 expression was correlated with CEP degeneration, immunohistochemical analysis of human CEP tissue was used to compare the level of EZH2 in normal and degenerated human CEP. It was found that the expression of EZH2 increased in degenerated human CEP (Fig. 1D and 1E). 31628324 chr16 72780389 72782389 ZFHX3 A third locus we examined is 16q22. The most highly AF_x0002_associated risk SNPs in this locus are found in the first intron of ZFHX3, which codes for a TF that plays key roles in development and in adult tissues56,57. human Musculature High+Lowthroughput Identification of atrial fibrillation associated genes and functional non-coding variants 是 rs281766 Arrhythmia muscle cell E_02_0176 Flow cytometry,PCR A third locus we examined is 16q22. The most highly AF_x0002_associated risk SNPs in this locus are found in the first intron of ZFHX3, which codes for a TF that plays key roles in development and in adult tissues56,57. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A third locus we examined is 16q22. The most highly AF_x0002_associated risk SNPs in this locus are found in the first intron of ZFHX3, which codes for a TF that plays key roles in development and in adult tissues56,57. Immunohistochemical staining A third locus we examined is 16q22. The most highly AF_x0002_associated risk SNPs in this locus are found in the first intron of ZFHX3, which codes for a TF that plays key roles in development and in adult tissues56,57. Flow cytometry,PCR ZFHX3 A third locus we examined is 16q22. The most highly AF_x0002_associated risk SNPs in this locus are found in the first intron of ZFHX3, which codes for a TF that plays key roles in development and in adult tissues56,57. 31626715 chr4 108044853 108046853 LEF1 Here we identify the EMT transcription factor LEF1 as a critical regulator of glutathione (GSH) metabolism aside from its well-known role as EMT inducer. human breast High+Lowthroughput LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer 否 mammary cancer breast cancer cell E_02_0177 Western blot,PCR,Flow cytometry Here we identify the EMT transcription factor LEF1 as a critical regulator of glutathione (GSH) metabolism aside from its well-known role as EMT inducer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we identify the EMT transcription factor LEF1 as a critical regulator of glutathione (GSH) metabolism aside from its well-known role as EMT inducer. Immunohistochemical staining Here we identify the EMT transcription factor LEF1 as a critical regulator of glutathione (GSH) metabolism aside from its well-known role as EMT inducer. Western blot,PCR,Flow cytometry LEF1 Here we identify the EMT transcription factor LEF1 as a critical regulator of glutathione (GSH) metabolism aside from its well-known role as EMT inducer. 31624269 chr14 95707296 95709296 TCL1A Wright et al.identified a total of 19 loci associated with mLOY9, including TCL1A and other genes involved in cell cycle regulation and DNA damage response. human blood High+Lowthroughput GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation 是 rs17758695 hematopoietic stem cell E_02_0178 Flow cytometry Wright et al.identified a total of 19 loci associated with mLOY9, including TCL1A and other genes involved in cell cycle regulation and DNA damage response. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Wright et al.identified a total of 19 loci associated with mLOY9, including TCL1A and other genes involved in cell cycle regulation and DNA damage response. Immunohistochemical staining Wright et al.identified a total of 19 loci associated with mLOY9, including TCL1A and other genes involved in cell cycle regulation and DNA damage response. Flow cytometry TCL1A Wright et al.identified a total of 19 loci associated with mLOY9, including TCL1A and other genes involved in cell cycle regulation and DNA damage response. 31624086 chr6 45325657 45327657 RUNX2 RUNX2 is a mammalian RUNT-related transcription factor (TF) required during embryogenesis for skeletal development and for the morphogenesis of many organs such as breast and thy_x0002_roid (13, 14). human connective High+Lowthroughput RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer 否 cancer cancer cell E_02_0179 Flow cytometry,PCR RUNX2 is a mammalian RUNT-related transcription factor (TF) required during embryogenesis for skeletal development and for the morphogenesis of many organs such as breast and thy_x0002_roid (13, 14). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RUNX2 is a mammalian RUNT-related transcription factor (TF) required during embryogenesis for skeletal development and for the morphogenesis of many organs such as breast and thy_x0002_roid (13, 14). Immunohistochemical staining RUNX2 is a mammalian RUNT-related transcription factor (TF) required during embryogenesis for skeletal development and for the morphogenesis of many organs such as breast and thy_x0002_roid (13, 14). Flow cytometry,PCR RUNX2 RUNX2 is a mammalian RUNT-related transcription factor (TF) required during embryogenesis for skeletal development and for the morphogenesis of many organs such as breast and thy_x0002_roid (13, 14). 31620967 chr12 6531445 6533445 GAPDH Membranes were incubated with primary antibody solution diluted 1:1000 in 5% (w/v) nonfat dry milk in TBS-T (mouse anti-ATP synthase subunit beta, ab14730, Abcam; rabbit anti-GAPDH, ab9485, Abcam; rabbit anti-ETFDH, ab91508, Abcam; human heart High+Lowthroughput One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats 否 Cardiac progenitor cell E_02_0180 PCR,Western blot Membranes were incubated with primary antibody solution diluted 1:1000 in 5% (w/v) nonfat dry milk in TBS-T (mouse anti-ATP synthase subunit beta, ab14730, Abcam; rabbit anti-GAPDH, ab9485, Abcam; rabbit anti-ETFDH, ab91508, Abcam; Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Membranes were incubated with primary antibody solution diluted 1:1000 in 5% (w/v) nonfat dry milk in TBS-T (mouse anti-ATP synthase subunit beta, ab14730, Abcam; rabbit anti-GAPDH, ab9485, Abcam; rabbit anti-ETFDH, ab91508, Abcam; Immunohistochemical staining Membranes were incubated with primary antibody solution diluted 1:1000 in 5% (w/v) nonfat dry milk in TBS-T (mouse anti-ATP synthase subunit beta, ab14730, Abcam; rabbit anti-GAPDH, ab9485, Abcam; rabbit anti-ETFDH, ab91508, Abcam; PCR,Western blot GAPDH Membranes were incubated with primary antibody solution diluted 1:1000 in 5% (w/v) nonfat dry milk in TBS-T (mouse anti-ATP synthase subunit beta, ab14730, Abcam; rabbit anti-GAPDH, ab9485, Abcam; rabbit anti-ETFDH, ab91508, Abcam; 31615655 chr17 39458277 39460277 CDK12 CDK12 is a transcription-related CDK that complexes with cyclinK to regulate gene transcription [6]. CDK12 has been demonstrated to be essential for DNA damage response (DDR), mRNA processing, and differentiation [7e9]. Several recent studies also implicated CDK12 in cancer pathology [10,11]. human thyroid High+Lowthroughput Targeting CDK12-mediated transcription regulation in anaplastic thyroid carcinoma 否 Anaplastic thyroid cancer Anaplastic thyroid carcinoma cell E_02_0181 PCR, Western blot, flow cytometry, immunofluorescence staining CDK12 is a transcription-related CDK that complexes with cyclinK to regulate gene transcription [6]. CDK12 has been demonstrated to be essential for DNA damage response (DDR), mRNA processing, and differentiation [7e9]. Several recent studies also implicated CDK12 in cancer pathology [10,11]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CDK12 is a transcription-related CDK that complexes with cyclinK to regulate gene transcription [6]. CDK12 has been demonstrated to be essential for DNA damage response (DDR), mRNA processing, and differentiation [7e9]. Several recent studies also implicated CDK12 in cancer pathology [10,11]. Immunohistochemical staining CDK12 is a transcription-related CDK that complexes with cyclinK to regulate gene transcription [6]. CDK12 has been demonstrated to be essential for DNA damage response (DDR), mRNA processing, and differentiation [7e9]. Several recent studies also implicated CDK12 in cancer pathology [10,11]. PCR,Western blot,Flow cytometry,免疫荧光染色 CDK12 CDK12 is a transcription-related CDK that complexes with cyclinK to regulate gene transcription [6]. CDK12 has been demonstrated to be essential for DNA damage response (DDR), mRNA processing, and differentiation [7e9]. Several recent studies also implicated CDK12 in cancer pathology [10,11]. 31615341 chr1 204393890 204395890 PPP1R15B However, levels of TGFβR1 did not show any change and therefore is possibly not a direct target of miR-98-5p. miR-98-5p also significantly decreased the mRNA levels of PPP1R15B (Figure 3(b)) further suggesting that this gene is targeted by miR-98-5p. human Epithelial High+Lowthroughput Circulatory miR-98-5p levels are deregulated during diabetes and it inhibits proliferation and promotes apoptosis by targeting PPP1R15B in keratinocytes 否 diabetes HaCaT cell E_02_0182 Flow cytometry,PCR,Western blot However, levels of TGFβR1 did not show any change and therefore is possibly not a direct target of miR-98-5p. miR-98-5p also significantly decreased the mRNA levels of PPP1R15B (Figure 3(b)) further suggesting that this gene is targeted by miR-98-5p. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, levels of TGFβR1 did not show any change and therefore is possibly not a direct target of miR-98-5p. miR-98-5p also significantly decreased the mRNA levels of PPP1R15B (Figure 3(b)) further suggesting that this gene is targeted by miR-98-5p. Immunohistochemical staining However, levels of TGFβR1 did not show any change and therefore is possibly not a direct target of miR-98-5p. miR-98-5p also significantly decreased the mRNA levels of PPP1R15B (Figure 3(b)) further suggesting that this gene is targeted by miR-98-5p. Flow cytometry,PCR,Western blot PPP1R15B However, levels of TGFβR1 did not show any change and therefore is possibly not a direct target of miR-98-5p. miR-98-5p also significantly decreased the mRNA levels of PPP1R15B (Figure 3(b)) further suggesting that this gene is targeted by miR-98-5p. 31614133 chr5 88713906 88715906 MEF2C Additionally, chromatin immunoprecipitation experiments and luciferase assays confirmed MEF2C interaction and direct binding of the CAIII promoter between -416 to -200 base pair. human Musculature High+Lowthroughput CAIII expression in skeletal muscle is regulated by Ca(2+)-CaMKII-MEF2C signaling 否 mouse cell of skeletal muscle E_02_0183 PCR,Western blot Additionally, chromatin immunoprecipitation experiments and luciferase assays confirmed MEF2C interaction and direct binding of the CAIII promoter between -416 to -200 base pair. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, chromatin immunoprecipitation experiments and luciferase assays confirmed MEF2C interaction and direct binding of the CAIII promoter between -416 to -200 base pair. Immunohistochemical staining Additionally, chromatin immunoprecipitation experiments and luciferase assays confirmed MEF2C interaction and direct binding of the CAIII promoter between -416 to -200 base pair. PCR,Western blot MEF2C,MEF2A Additionally, chromatin immunoprecipitation experiments and luciferase assays confirmed MEF2C interaction and direct binding of the CAIII promoter between -416 to -200 base pair.;Therefore, we evaluated the role of different MEF2 homologs in CAIII expression. Plasmids containing RNAi sequences targeting MEF2A, MEF2C, and MEF2D were transfected into C2C12 cells, and CAIII expression was evaluated. 31606392 chr1 247413593 247415593 NLRP3 Several experiments have confirmed that changes in intracellular ion concentration and the content of reactive oxygen species (ROS) play an important role in the activation of the NLRP3 inflammasome, while inhibition of Ca2+ inflow/K+ outflow and decreased ROS production can block the activation of NLRP3 to a certain extent [18-21]. human blood High+Lowthroughput Nickel-refining fumes induce NLRP3 activation dependent on mitochondrial damage and ROS production in Beas-2B cells 否 inflammation B cell E_02_0184 PCR, Western blot, immunofluorescence staining Several experiments have confirmed that changes in intracellular ion concentration and the content of reactive oxygen species (ROS) play an important role in the activation of the NLRP3 inflammasome, while inhibition of Ca2+ inflow/K+ outflow and decreased ROS production can block the activation of NLRP3 to a certain extent [18-21]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Several experiments have confirmed that changes in intracellular ion concentration and the content of reactive oxygen species (ROS) play an important role in the activation of the NLRP3 inflammasome, while inhibition of Ca2+ inflow/K+ outflow and decreased ROS production can block the activation of NLRP3 to a certain extent [18-21]. Immunohistochemical staining Several experiments have confirmed that changes in intracellular ion concentration and the content of reactive oxygen species (ROS) play an important role in the activation of the NLRP3 inflammasome, while inhibition of Ca2+ inflow/K+ outflow and decreased ROS production can block the activation of NLRP3 to a certain extent [18-21]. PCR,Western blot,免疫荧光染色 NLRP3 Several experiments have confirmed that changes in intracellular ion concentration and the content of reactive oxygen species (ROS) play an important role in the activation of the NLRP3 inflammasome, while inhibition of Ca2+ inflow/K+ outflow and decreased ROS production can block the activation of NLRP3 to a certain extent [18-21]. 31601918 chr7 44101861 44103861 AEBP1 We had observed earlier that adipocyte enhancer binding protein 1 (AEBP1) expression to be up-regulated in primary GBMs as opposed to progressive secondary GBMs through transcriptome analysis1 . human Nervous High+Lowthroughput AEBP1 down regulation induced cell death pathway depends on PTEN status of glioma cells 否 tumour glioma cell E_02_0185 PCR, Western blot, immunofluorescence light staining, flow cytometry We had observed earlier that adipocyte enhancer binding protein 1 (AEBP1) expression to be up-regulated in primary GBMs as opposed to progressive secondary GBMs through transcriptome analysis1 . Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We had observed earlier that adipocyte enhancer binding protein 1 (AEBP1) expression to be up-regulated in primary GBMs as opposed to progressive secondary GBMs through transcriptome analysis1 . Immunohistochemical staining We had observed earlier that adipocyte enhancer binding protein 1 (AEBP1) expression to be up-regulated in primary GBMs as opposed to progressive secondary GBMs through transcriptome analysis1 . PCR,Western blot,免疫荧光光染色,Flow cytometry AEBP1 We had observed earlier that adipocyte enhancer binding protein 1 (AEBP1) expression to be up-regulated in primary GBMs as opposed to progressive secondary GBMs through transcriptome analysis1 . 31601151 chr11 35136538 35138538 CD44 The expression levels of ASCs markers CD44, SMA, and Vimentin were decreased dur_x0002_ing the differentiation process (Figure 2(Ea–c)). human connective High+Lowthroughput Cl- channels regulate lipid droplet formation via Rab8a expression during adipocyte differentiation 否 stem cell E_02_0186 PCR, flow cytometry, Western blot, immunofluorescence staining The expression levels of ASCs markers CD44, SMA, and Vimentin were decreased dur_x0002_ing the differentiation process (Figure 2(Ea–c)). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression levels of ASCs markers CD44, SMA, and Vimentin were decreased dur_x0002_ing the differentiation process (Figure 2(Ea–c)). Immunohistochemical staining The expression levels of ASCs markers CD44, SMA, and Vimentin were decreased dur_x0002_ing the differentiation process (Figure 2(Ea–c)). PCR,Flow cytometry,Western blot,免疫荧光染色 CD44,NPPB The expression levels of ASCs markers CD44, SMA, and Vimentin were decreased dur_x0002_ing the differentiation process (Figure 2(Ea–c)).;The morphology of the differentiated cells treated with NPPB was similar to that of those untreated with NPPB (Figure 3(Aa and b)). 31598701 chr7 55016371 55018371 EGFR Other relevant genes such as EGFR and BCL-X, also known to be regulated by pro_x0002_gestins (56,64) exhibited a similar transcriptional activity in response to R5020 in both cell lines (Supplementary Figure S4B), pointing to a gene-specific GR-PR modulation. human breast High+Lowthroughput Exogenous pyruvate represses histone gene expression and inhibits cancer cell proliferation via the NAMPT-NAD+-SIRT1 pathway 否 mammary cancer breast cancer cell E_02_0187 PCR,Flow cytometry,Western blot Other relevant genes such as EGFR and BCL-X, also known to be regulated by pro_x0002_gestins (56,64) exhibited a similar transcriptional activity in response to R5020 in both cell lines (Supplementary Figure S4B), pointing to a gene-specific GR-PR modulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Other relevant genes such as EGFR and BCL-X, also known to be regulated by pro_x0002_gestins (56,64) exhibited a similar transcriptional activity in response to R5020 in both cell lines (Supplementary Figure S4B), pointing to a gene-specific GR-PR modulation. Immunohistochemical staining Other relevant genes such as EGFR and BCL-X, also known to be regulated by pro_x0002_gestins (56,64) exhibited a similar transcriptional activity in response to R5020 in both cell lines (Supplementary Figure S4B), pointing to a gene-specific GR-PR modulation. PCR,Flow cytometry,Western blot EGFR Other relevant genes such as EGFR and BCL-X, also known to be regulated by pro_x0002_gestins (56,64) exhibited a similar transcriptional activity in response to R5020 in both cell lines (Supplementary Figure S4B), pointing to a gene-specific GR-PR modulation. 31592235 chr12 57744934 57746934 CDK4 Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels. human Musculature High+Lowthroughput P21 and P27 promote tumorigenesis and progression via cell cycle acceleration in seminal vesicles of TRAMP mice 否 prostatic cancer smooth muscle cell E_02_0188 Western blot Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels. Immunohistochemical staining Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels. Western blot CDK4,EGFR Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels.;The results indicated that EGFR, AKT, STAT3, and EZH2 all play a crucial role in promoting cell proliferation and tumor growth in seminal vesicles of TRAMP mice. 31592229 chr7 148804549 148806549 EZH2 In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). human intestine High+Lowthroughput Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2 否 Infectious gastroenteritis porcine intestinal epthelial cell E_02_0189 Western blot, flow cytometry, PCR, immunofluorescence staining In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Immunohistochemical staining In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Western blot,Flow cytometry,PCR,免疫荧光染色 EZH2,KAT6B,HK2 In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2).;miR-22 has a strong correlation with NF-κB pathway and mitochondrial damage. Recently, it was reported that miR-22 inhibited PI3K/Akt/NF-κB signaling in tongue squamous cell carcinoma (TSCC) cells via targeting KAT6B[22].;However, HK2 does not regulate NK-κB activation. Not only HK2, IL-6 was also identified as the target of miR-22 and suppressed TGEV-induced mPTP opening via activating NF-κB pathway, suggesting that miR-22 regulates TGEV-induced mPTP opening via at least two pathways. 31591447 chr4 53777000 53779000 Tal2 We first analyzed gene expression dynamics during the development of each lineage (Fig. 1b–e; Supplementary informa_x0002_tion, Table S2) and found that expression of ectodermal genes (e.g., Tal2 and Lhx5), mesendodermal genes mouse Epithelial High+Lowthroughput Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development 否 anterior epiblast cell E_02_0190 Flow cytometry,PCR We first analyzed gene expression dynamics during the development of each lineage (Fig. 1b–e; Supplementary informa_x0002_tion, Table S2) and found that expression of ectodermal genes (e.g., Tal2 and Lhx5), mesendodermal genes Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We first analyzed gene expression dynamics during the development of each lineage (Fig. 1b–e; Supplementary informa_x0002_tion, Table S2) and found that expression of ectodermal genes (e.g., Tal2 and Lhx5), mesendodermal genes Immunohistochemical staining We first analyzed gene expression dynamics during the development of each lineage (Fig. 1b–e; Supplementary informa_x0002_tion, Table S2) and found that expression of ectodermal genes (e.g., Tal2 and Lhx5), mesendodermal genes Flow cytometry,PCR Tal2,Lhx5,Sox2,Mesp1 We first analyzed gene expression dynamics during the development of each lineage (Fig. 1b–e; Supplementary informa_x0002_tion, Table S2) and found that expression of ectodermal genes (e.g., Tal2 and Lhx5), mesendodermal genes;We first analyzed gene expression dynamics during the development of each lineage (Fig. 1b–e; Supplementary informa_x0002_tion, Table S2) and found that expression of ectodermal genes (e.g., Tal2 and Lhx5), mesendodermal genes;These gastrula-specific enhancer bins were enriched near genes that are related to embryonic pattern formation, gastrulation and primary germ layer specification, and are highly expressed at the gastrulation stage, such as Sox2, Eomes and Mesp1 (Fig. 5b–e).;These gastrula-specific enhancer bins were enriched near genes that are related to embryonic pattern formation, gastrulation and primary germ layer specification, and are highly expressed at the gastrulation stage, such as Sox2, Eomes and Mesp1 (Fig. 5b–e). 31589602 chr12 80713954 80715954 MYF5 We also compared motifs within H3K27ac or ATAC-seq peaks and found similar representations of jun proto-oncogene (JUN), myogenic factor 5 (MYF5), MEF2, specificity protein 1 (SP1), nuclear transcription fac_x0002_tor Y (NFY), and E-twenty-six family transcription factor (ETS) elements in MT and Quad, whereas factors critical for progenitor functions including runt-related transcription factor (RUNX), paired box (PAX), and TEA domain transcription factor 1 (TEAD) were more con_x0002_centrated in MT (Fig 4G). human blood High+Lowthroughput Dynamic enhancers control skeletal muscle identity and reprogramming 否 cancer T cell E_02_0191 Flow cytometry,PCR We also compared motifs within H3K27ac or ATAC-seq peaks and found similar representations of jun proto-oncogene (JUN), myogenic factor 5 (MYF5), MEF2, specificity protein 1 (SP1), nuclear transcription fac_x0002_tor Y (NFY), and E-twenty-six family transcription factor (ETS) elements in MT and Quad, whereas factors critical for progenitor functions including runt-related transcription factor (RUNX), paired box (PAX), and TEA domain transcription factor 1 (TEAD) were more con_x0002_centrated in MT (Fig 4G). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also compared motifs within H3K27ac or ATAC-seq peaks and found similar representations of jun proto-oncogene (JUN), myogenic factor 5 (MYF5), MEF2, specificity protein 1 (SP1), nuclear transcription fac_x0002_tor Y (NFY), and E-twenty-six family transcription factor (ETS) elements in MT and Quad, whereas factors critical for progenitor functions including runt-related transcription factor (RUNX), paired box (PAX), and TEA domain transcription factor 1 (TEAD) were more con_x0002_centrated in MT (Fig 4G). Immunohistochemical staining We also compared motifs within H3K27ac or ATAC-seq peaks and found similar representations of jun proto-oncogene (JUN), myogenic factor 5 (MYF5), MEF2, specificity protein 1 (SP1), nuclear transcription fac_x0002_tor Y (NFY), and E-twenty-six family transcription factor (ETS) elements in MT and Quad, whereas factors critical for progenitor functions including runt-related transcription factor (RUNX), paired box (PAX), and TEA domain transcription factor 1 (TEAD) were more con_x0002_centrated in MT (Fig 4G). Flow cytometry,PCR MYF5 We also compared motifs within H3K27ac or ATAC-seq peaks and found similar representations of jun proto-oncogene (JUN), myogenic factor 5 (MYF5), MEF2, specificity protein 1 (SP1), nuclear transcription fac_x0002_tor Y (NFY), and E-twenty-six family transcription factor (ETS) elements in MT and Quad, whereas factors critical for progenitor functions including runt-related transcription factor (RUNX), paired box (PAX), and TEA domain transcription factor 1 (TEAD) were more con_x0002_centrated in MT (Fig 4G). 31588020 chr17 39685586 39687586 ERBB2 However, the National Comprehensive Can_x0002_cer Network guidelines for non-small cell lung cancer (NSCLC) recommend that newly diagnosed patients undergo broad mo_x0002_lecular profiling to detect ERBB2 mutations (Ettinger et al., 2018). human blood High+Lowthroughput Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity 否 cancer Ba/F3 cell E_02_0192 PCR,Western blot However, the National Comprehensive Can_x0002_cer Network guidelines for non-small cell lung cancer (NSCLC) recommend that newly diagnosed patients undergo broad mo_x0002_lecular profiling to detect ERBB2 mutations (Ettinger et al., 2018). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, the National Comprehensive Can_x0002_cer Network guidelines for non-small cell lung cancer (NSCLC) recommend that newly diagnosed patients undergo broad mo_x0002_lecular profiling to detect ERBB2 mutations (Ettinger et al., 2018). Immunohistochemical staining However, the National Comprehensive Can_x0002_cer Network guidelines for non-small cell lung cancer (NSCLC) recommend that newly diagnosed patients undergo broad mo_x0002_lecular profiling to detect ERBB2 mutations (Ettinger et al., 2018). PCR,Western blot ERBB2 However, the National Comprehensive Can_x0002_cer Network guidelines for non-small cell lung cancer (NSCLC) recommend that newly diagnosed patients undergo broad mo_x0002_lecular profiling to detect ERBB2 mutations (Ettinger et al., 2018). 31586043 chr5 1389936 1391936 SLC6A3 Many environmental factors can regulate dopaminergic (DAergic) activity including SLC6A3, the gene encoding the dopamine transporter (DAT)1–7 . human Nervous High+Lowthroughput Identification of HIVEP2 as a dopaminergic transcription factor related to substance use disorders in rats and humans 是 rs67175440 Immunodeficiencies SH-SH5Y cell E_02_0193 PCR,Western blot Many environmental factors can regulate dopaminergic (DAergic) activity including SLC6A3, the gene encoding the dopamine transporter (DAT)1–7 . Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Many environmental factors can regulate dopaminergic (DAergic) activity including SLC6A3, the gene encoding the dopamine transporter (DAT)1–7 . Immunohistochemical staining Many environmental factors can regulate dopaminergic (DAergic) activity including SLC6A3, the gene encoding the dopamine transporter (DAT)1–7 . PCR,Western blot SLC6A3,PITX3 Many environmental factors can regulate dopaminergic (DAergic) activity including SLC6A3, the gene encoding the dopamine transporter (DAT)1–7 .;Recently, several TFs for SLC6A3 have been cloned, including Nurr1 (NR4A2), paired-like homeobox 3 pro_x0002_tein (PITX3), HEY1, SP1, SP3, AZI23′UTR, SRP54, and Nfe2l18–13. 31586032 chr16 67559931 67561931 CTCF Since enhancer-promoter looping is mediated by various transcription factors (69) and chromatin remodelers such as Mediator, Cohesin (70), CTCF proteins (71) and YY1(72), it is possible that the acidic and PEST domains interact with different factors to establish enhancer_x0002_promoter interactions in a gene and cell type_x0002_specific manner. human tumour High+Lowthroughput The transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1β eRNA and mRNA transcription in mouse melanoma and macrophage cell lines 否 tumour melanoma cells E_02_0194 PCR,Western blot,Flow cytometry Since enhancer-promoter looping is mediated by various transcription factors (69) and chromatin remodelers such as Mediator, Cohesin (70), CTCF proteins (71) and YY1(72), it is possible that the acidic and PEST domains interact with different factors to establish enhancer_x0002_promoter interactions in a gene and cell type_x0002_specific manner. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Since enhancer-promoter looping is mediated by various transcription factors (69) and chromatin remodelers such as Mediator, Cohesin (70), CTCF proteins (71) and YY1(72), it is possible that the acidic and PEST domains interact with different factors to establish enhancer_x0002_promoter interactions in a gene and cell type_x0002_specific manner. Immunohistochemical staining Since enhancer-promoter looping is mediated by various transcription factors (69) and chromatin remodelers such as Mediator, Cohesin (70), CTCF proteins (71) and YY1(72), it is possible that the acidic and PEST domains interact with different factors to establish enhancer_x0002_promoter interactions in a gene and cell type_x0002_specific manner. PCR,Western blot,Flow cytometry CTCF Since enhancer-promoter looping is mediated by various transcription factors (69) and chromatin remodelers such as Mediator, Cohesin (70), CTCF proteins (71) and YY1(72), it is possible that the acidic and PEST domains interact with different factors to establish enhancer_x0002_promoter interactions in a gene and cell type_x0002_specific manner. 31585804 chrX 100840244 100842244 NOX1 Endo_x0002_thelial cells express 4 ROS-generating NOX isoforms (eg, NOX1, NOX2, NOX4, and NOX5). human Epithelial High+Lowthroughput Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress 否 atherosclerosis endothelial cell E_02_0195 PCR Endo_x0002_thelial cells express 4 ROS-generating NOX isoforms (eg, NOX1, NOX2, NOX4, and NOX5). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Endo_x0002_thelial cells express 4 ROS-generating NOX isoforms (eg, NOX1, NOX2, NOX4, and NOX5). Immunohistochemical staining Endo_x0002_thelial cells express 4 ROS-generating NOX isoforms (eg, NOX1, NOX2, NOX4, and NOX5). PCR NOX1 Endo_x0002_thelial cells express 4 ROS-generating NOX isoforms (eg, NOX1, NOX2, NOX4, and NOX5). 31585741 chrX 48506512 48508512 PORCN To explore kidney_x0002_specific functions of PORCN in UUO pathogenesis, we first confirmed that expression of Wnt pathway components were induced in the obstructed kidney human bone High+Lowthroughput Opposing actions of renal tubular- and myeloid-derived porcupine in obstruction-induced?kidney fibrosis 否 infiltrating myeloid cell E_02_0196 PCR,Western blot To explore kidney_x0002_specific functions of PORCN in UUO pathogenesis, we first confirmed that expression of Wnt pathway components were induced in the obstructed kidney Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To explore kidney_x0002_specific functions of PORCN in UUO pathogenesis, we first confirmed that expression of Wnt pathway components were induced in the obstructed kidney Immunohistochemical staining To explore kidney_x0002_specific functions of PORCN in UUO pathogenesis, we first confirmed that expression of Wnt pathway components were induced in the obstructed kidney PCR,Western blot PORCN,Axin2 To explore kidney_x0002_specific functions of PORCN in UUO pathogenesis, we first confirmed that expression of Wnt pathway components were induced in the obstructed kidney;Accordingly, ablation of PORCN in the obstructed KKO kidneys led not only to reduced expression of Wnt target genes, Axin2 and Nkd1, but also several Wnt ligands including Wnt3, Wnt4, Wnt7a, and Wnt9b. 31579944 chr7 148804427 148806427 EZH2 Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers. human Epithelial High+Lowthroughput Genetic or pharmacologic blockade of enhancer of zeste homolog 2 inhibits the progression of peritoneal fibrosis 否 cancer peritoneal mesothelial cell E_02_0197 PCR, Western blot, immunofluorescence staining Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers. Immunohistochemical staining Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers. PCR,Western blot,免疫荧光染色 EZH2,TIMP2,STAT3 Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers.;Moreover, delayed administration of 3-DZNeP inhibited peritoneal fibrosis progression, reversed established peritoneal fibrosis and reduced expression of tissue inhibitor of metalloproteinase 2 (TIMP2), and matrix metalloproteinase-2 and -9. ;Therefore, we speculated that EZH2 blockade suppressed the MMP2 by inhibiting the EZH2- STAT3 signaling axis. In addition, genome wide approaches suggest that EZH2 targets Fosl1 and Klf5, two activators of MMP9 [40]. 31575636 chr22 41830453 41832453 SREBF2 Among the cholesterol biosynthetic genes,we observed upregulation during mid-regeneration (4-7 dpi) of SREBF2, a known cholesterol master-regulatory transcription factor (Madison 2016; Smith et al. 2018). human High+Lowthroughput Regeneration Rosetta: An Interactive Web Application To Explore Regeneration-Associated Gene Expression and Chromatin Accessibility 否 E_02_0198 RNA-seq Among the cholesterol biosynthetic genes,we observed upregulation during mid-regeneration (4-7 dpi) of SREBF2, a known cholesterol master-regulatory transcription factor (Madison 2016; Smith et al. 2018). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Among the cholesterol biosynthetic genes,we observed upregulation during mid-regeneration (4-7 dpi) of SREBF2, a known cholesterol master-regulatory transcription factor (Madison 2016; Smith et al. 2018). Immunohistochemical staining Among the cholesterol biosynthetic genes,we observed upregulation during mid-regeneration (4-7 dpi) of SREBF2, a known cholesterol master-regulatory transcription factor (Madison 2016; Smith et al. 2018). RNA-seq SREBF2 Among the cholesterol biosynthetic genes,we observed upregulation during mid-regeneration (4-7 dpi) of SREBF2, a known cholesterol master-regulatory transcription factor (Madison 2016; Smith et al. 2018). 31570000 chr19 10651535 10653535 ILF3 The presence of multiple additional ILF3 binding interac_x0002_tions with introns, coding exons, noncoding non-AS exons, and SINEs on the transcribed strand probably reflects the extensive functional diversity of the ILF3 gene in addition to an incomplete annotation of the transcriptome. human High+Lowthroughput The RNA-binding protein ILF3 binds to transposable element sequences in SINEUP lncRNAs 否 liver cancer DH5a cells E_02_0199 Western blot,Flow cytometry,PCR The presence of multiple additional ILF3 binding interac_x0002_tions with introns, coding exons, noncoding non-AS exons, and SINEs on the transcribed strand probably reflects the extensive functional diversity of the ILF3 gene in addition to an incomplete annotation of the transcriptome. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The presence of multiple additional ILF3 binding interac_x0002_tions with introns, coding exons, noncoding non-AS exons, and SINEs on the transcribed strand probably reflects the extensive functional diversity of the ILF3 gene in addition to an incomplete annotation of the transcriptome. Immunohistochemical staining The presence of multiple additional ILF3 binding interac_x0002_tions with introns, coding exons, noncoding non-AS exons, and SINEs on the transcribed strand probably reflects the extensive functional diversity of the ILF3 gene in addition to an incomplete annotation of the transcriptome. Western blot,Flow cytometry,PCR ILF3 The presence of multiple additional ILF3 binding interac_x0002_tions with introns, coding exons, noncoding non-AS exons, and SINEs on the transcribed strand probably reflects the extensive functional diversity of the ILF3 gene in addition to an incomplete annotation of the transcriptome. 31562697 chr3 69736600 69738600 MITF MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, en_x0002_codes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. human connective High+Lowthroughput Delineating the role of MITF isoforms in pigmentation and tissue homeostasis 否 Melanoma Pigment Cell E_02_0200 PCR, Western blot, immunofluorescence staining MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, en_x0002_codes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, en_x0002_codes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. Immunohistochemical staining MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, en_x0002_codes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. PCR,Western blot,免疫荧光染色 MITF,TYR MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, en_x0002_codes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini.;We previously showed that 9‐cis retinoic acid upregulates MITF and TYR expression in cultured melanocytes, stimulating pigment production in melano_x0002_cyte and melanoma cell lines (Paterson, Ho, Kapadia, & Ganesan, 2013). 31558567 chrX 47579564 47581564 TIMP1 Among the 40 chemo_x0002_kines/cytokines we analyzed, nine were consistently up_x0002_regulated in Lats1/2 CKO sham hearts, including TIMP1, CXCL1, CXCL12, and CSF1. human bone High+Lowthroughput Hippo pathway deletion in adult resting cardiac fibroblasts initiates a cell state transition with spontaneous and self-sustaining fibrosis 否 miocardial infarction myeloid cell E_02_0201 PCR, flow cytometry, gene knockdown Among the 40 chemo_x0002_kines/cytokines we analyzed, nine were consistently up_x0002_regulated in Lats1/2 CKO sham hearts, including TIMP1, CXCL1, CXCL12, and CSF1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Among the 40 chemo_x0002_kines/cytokines we analyzed, nine were consistently up_x0002_regulated in Lats1/2 CKO sham hearts, including TIMP1, CXCL1, CXCL12, and CSF1. Immunohistochemical staining Among the 40 chemo_x0002_kines/cytokines we analyzed, nine were consistently up_x0002_regulated in Lats1/2 CKO sham hearts, including TIMP1, CXCL1, CXCL12, and CSF1. PCR,Flow cytometry,基因敲降 TIMP1 Among the 40 chemo_x0002_kines/cytokines we analyzed, nine were consistently up_x0002_regulated in Lats1/2 CKO sham hearts, including TIMP1, CXCL1, CXCL12, and CSF1. 31551362 chr3 181709186 181711186 SOX2 We proposed SOX2 as a lineage_x0002_survival oncogene in squamous cell cancers for its essential role during the development in the specification of the squamous cell lineages by opposing the role of Nkx2-1 in the dividing foregut and its essentiality for LUSC cell survival (9). human lung High+Lowthroughput Epigenomic Profiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma 是 Lung squamous cell carcinoma Lung squamous cell E_02_0202 PCR, Western blot, flow cytometry, immunofluorescence staining We proposed SOX2 as a lineage_x0002_survival oncogene in squamous cell cancers for its essential role during the development in the specification of the squamous cell lineages by opposing the role of Nkx2-1 in the dividing foregut and its essentiality for LUSC cell survival (9). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We proposed SOX2 as a lineage_x0002_survival oncogene in squamous cell cancers for its essential role during the development in the specification of the squamous cell lineages by opposing the role of Nkx2-1 in the dividing foregut and its essentiality for LUSC cell survival (9). Immunohistochemical staining We proposed SOX2 as a lineage_x0002_survival oncogene in squamous cell cancers for its essential role during the development in the specification of the squamous cell lineages by opposing the role of Nkx2-1 in the dividing foregut and its essentiality for LUSC cell survival (9). PCR,Western blot,Flow cytometry,免疫荧光染色 SOX2,POU3F2 We proposed SOX2 as a lineage_x0002_survival oncogene in squamous cell cancers for its essential role during the development in the specification of the squamous cell lineages by opposing the role of Nkx2-1 in the dividing foregut and its essentiality for LUSC cell survival (9).;For the TCGA-LUSC RNA-seq data, the 501 LUSC tumor tissues were classified on the basis of the expression level of TP63, SOX2, and POU3F2. 31550664 chr17 13222491 13224491 Sod2 Specifically, we used Mn2+-superoxide dismutase (Sod2) deficient mice, in which oxidative stress is significantly increased even in a heterozygous state [6]. mouse pancreas High+Lowthroughput Gestational oxidative stress protects against adult obesity and insulin resistance 否 Pancreatic β - cell dysfunction Beta cell E_02_0203 PCR Specifically, we used Mn2+-superoxide dismutase (Sod2) deficient mice, in which oxidative stress is significantly increased even in a heterozygous state [6]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Specifically, we used Mn2+-superoxide dismutase (Sod2) deficient mice, in which oxidative stress is significantly increased even in a heterozygous state [6]. Immunohistochemical staining Specifically, we used Mn2+-superoxide dismutase (Sod2) deficient mice, in which oxidative stress is significantly increased even in a heterozygous state [6]. PCR Sod2 Specifically, we used Mn2+-superoxide dismutase (Sod2) deficient mice, in which oxidative stress is significantly increased even in a heterozygous state [6]. 31548608 chr9 107481891 107483891 KLF4 The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22 human connective High+Lowthroughput KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks 否 pluripotent stem cell E_02_0204 Western blot,PCR,Flow cytometry The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22 Immunohistochemical staining The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22 Western blot,PCR,Flow cytometry KLF4,Pou5f1,HOPX The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22;The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22;The architectural function of KLF4 is further supported by the observations that KLF4 depletion abrogates long-range chromatin contacts at specific genomic loci, such as the Pou5f1 (Oct4) locus in mouse PSCs18 and the HOPX gene in human epidermal keratinocytes22 31547433 chr13 40553074 40555074 FOXO1 The forkhead box protein class O type 1 (FOXO1) also participates in adipogenesis, by preventing adipose tissue differentiation through the inhibition of PPAR-γ transcription. human connective High+Lowthroughput Transcriptional Analysis of FOXO1, C/EBP-α and PPAR-γ2 Genes and Their Association with Obesity-Related Insulin Resistance 否 Obesity NIH-3T3 fibroblastic cell E_02_0205 Western blot,PCR The forkhead box protein class O type 1 (FOXO1) also participates in adipogenesis, by preventing adipose tissue differentiation through the inhibition of PPAR-γ transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The forkhead box protein class O type 1 (FOXO1) also participates in adipogenesis, by preventing adipose tissue differentiation through the inhibition of PPAR-γ transcription. Immunohistochemical staining The forkhead box protein class O type 1 (FOXO1) also participates in adipogenesis, by preventing adipose tissue differentiation through the inhibition of PPAR-γ transcription. Western blot,PCR FOXO1 The forkhead box protein class O type 1 (FOXO1) also participates in adipogenesis, by preventing adipose tissue differentiation through the inhibition of PPAR-γ transcription. 31546863 chr11 36480909 36482909 TRAF6 sion of the proteins involved in osteoclastogenesis including TRAF6, c-Fos, NFATc1, and cathepsin K. Western blotting indicated that RANKL significantly increased the expression of TRAF6, NFATc1, and cathepsin K. Pre-treatm human blood High+Lowthroughput Egg White Ovotransferrin Attenuates RANKL-Induced Osteoclastogenesis and Bone Resorption 否 osteoporosis B cell E_02_0206 Western blot,PCR sion of the proteins involved in osteoclastogenesis including TRAF6, c-Fos, NFATc1, and cathepsin K. Western blotting indicated that RANKL significantly increased the expression of TRAF6, NFATc1, and cathepsin K. Pre-treatm Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq sion of the proteins involved in osteoclastogenesis including TRAF6, c-Fos, NFATc1, and cathepsin K. Western blotting indicated that RANKL significantly increased the expression of TRAF6, NFATc1, and cathepsin K. Pre-treatm Immunohistochemical staining sion of the proteins involved in osteoclastogenesis including TRAF6, c-Fos, NFATc1, and cathepsin K. Western blotting indicated that RANKL significantly increased the expression of TRAF6, NFATc1, and cathepsin K. Pre-treatm Western blot,PCR TRAF6 sion of the proteins involved in osteoclastogenesis including TRAF6, c-Fos, NFATc1, and cathepsin K. Western blotting indicated that RANKL significantly increased the expression of TRAF6, NFATc1, and cathepsin K. Pre-treatm 31546763 chr4 77508709 77510709 CXCL13 During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. human blood High+Lowthroughput Heightened TLR7/9-Induced IL-10 and CXCL13 Production with Dysregulated NF-?B Activation in CD11c(hi)CD11b(+) Dendritic Cells in NZB/W F1 Mice 否 Systemic lupus erythematosus T cell E_02_0207 Western blot,PCR,Flow cytometry During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. Immunohistochemical staining During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. Western blot,PCR,Flow cytometry CXCL13 During the disease state, this subset of mDCs displayed heightened toll-like receptors 7 and 9 (TLR 7/9) responses with increased interleukin 10 (IL-10) and C-X-C motif chemokine ligand 13 (CXCL13) expressions. 31546150 chr16 68734373 68736373 CDH1 EMT is a process in which epithelial cells lose their cell junctions and polarity characterized by E-cadherin (CDH1) downregulation to gain a motile mesenchymal phenotype, in_x0002_duction of a series of mesenchymal-specific transcription factors, such as Snail1, Snail2, ZEB1, ZEB2 and Twist1. human pancreas High+Lowthroughput Menin Coordinates C/EBPβ-Mediated TGF-β Signaling for Epithelial-Mesenchymal Transition and Growth Inhibition in Pancreatic Cancer 否 Pancreatic ductal adenocarcinoma PANC1 cells E_02_0208 Western blot,PCR,Flow cytometry EMT is a process in which epithelial cells lose their cell junctions and polarity characterized by E-cadherin (CDH1) downregulation to gain a motile mesenchymal phenotype, in_x0002_duction of a series of mesenchymal-specific transcription factors, such as Snail1, Snail2, ZEB1, ZEB2 and Twist1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EMT is a process in which epithelial cells lose their cell junctions and polarity characterized by E-cadherin (CDH1) downregulation to gain a motile mesenchymal phenotype, in_x0002_duction of a series of mesenchymal-specific transcription factors, such as Snail1, Snail2, ZEB1, ZEB2 and Twist1. Immunohistochemical staining EMT is a process in which epithelial cells lose their cell junctions and polarity characterized by E-cadherin (CDH1) downregulation to gain a motile mesenchymal phenotype, in_x0002_duction of a series of mesenchymal-specific transcription factors, such as Snail1, Snail2, ZEB1, ZEB2 and Twist1. Western blot,PCR,Flow cytometry CDH1 EMT is a process in which epithelial cells lose their cell junctions and polarity characterized by E-cadherin (CDH1) downregulation to gain a motile mesenchymal phenotype, in_x0002_duction of a series of mesenchymal-specific transcription factors, such as Snail1, Snail2, ZEB1, ZEB2 and Twist1. 31546122 chr11 120694060 120696060 Fasn We also measured the expression of adiponectin (Adipoq), li_x0002_poprotein lipase (Lpl), and fatty acid synthase (Fasn), which were reported to be used as adipogenesis markers, and the results showed that the DINP exposure induced the upregulation of Adipoq and Lpl, however, unlike Rosi, the Fasn was not significantly affected with DINP exposure (Fig. S4). mouse connective High+Lowthroughput Promoting differentiation and lipid metabolism are the primary effects for DINP exposure on 3T3-L1 preadipocytes 否 3T3-L1 cell E_02_0209 PCR,Western blot,Flow cytometry We also measured the expression of adiponectin (Adipoq), li_x0002_poprotein lipase (Lpl), and fatty acid synthase (Fasn), which were reported to be used as adipogenesis markers, and the results showed that the DINP exposure induced the upregulation of Adipoq and Lpl, however, unlike Rosi, the Fasn was not significantly affected with DINP exposure (Fig. S4). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We also measured the expression of adiponectin (Adipoq), li_x0002_poprotein lipase (Lpl), and fatty acid synthase (Fasn), which were reported to be used as adipogenesis markers, and the results showed that the DINP exposure induced the upregulation of Adipoq and Lpl, however, unlike Rosi, the Fasn was not significantly affected with DINP exposure (Fig. S4). Immunohistochemical staining We also measured the expression of adiponectin (Adipoq), li_x0002_poprotein lipase (Lpl), and fatty acid synthase (Fasn), which were reported to be used as adipogenesis markers, and the results showed that the DINP exposure induced the upregulation of Adipoq and Lpl, however, unlike Rosi, the Fasn was not significantly affected with DINP exposure (Fig. S4). PCR,Western blot,Flow cytometry Fasn,Adipoq We also measured the expression of adiponectin (Adipoq), li_x0002_poprotein lipase (Lpl), and fatty acid synthase (Fasn), which were reported to be used as adipogenesis markers, and the results showed that the DINP exposure induced the upregulation of Adipoq and Lpl, however, unlike Rosi, the Fasn was not significantly affected with DINP exposure (Fig. S4).;We also measured the expression of adiponectin (Adipoq), li_x0002_poprotein lipase (Lpl), and fatty acid synthase (Fasn), which were reported to be used as adipogenesis markers, and the results showed that the DINP exposure induced the upregulation of Adipoq and Lpl, however, unlike Rosi, the Fasn was not significantly affected with DINP exposure (Fig. S4). 31544892 chr13 30453885 30455885 HMGB1 In this study, we examined the role of Ig and Ek enhancers in enhancing SHM in the episomal vector pCEP4 that expresses an anti-high mobility group box 1 (HMGB1) full-length antibody. human ovary High+Lowthroughput Enhancers Improve the AID-Induced Hypermutation in Episomal Vector for Antibody Affinity Maturation in Mammalian Cell Display 否 cancer CHO cells E_02_0210 Flow cytometry In this study, we examined the role of Ig and Ek enhancers in enhancing SHM in the episomal vector pCEP4 that expresses an anti-high mobility group box 1 (HMGB1) full-length antibody. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we examined the role of Ig and Ek enhancers in enhancing SHM in the episomal vector pCEP4 that expresses an anti-high mobility group box 1 (HMGB1) full-length antibody. Immunohistochemical staining In this study, we examined the role of Ig and Ek enhancers in enhancing SHM in the episomal vector pCEP4 that expresses an anti-high mobility group box 1 (HMGB1) full-length antibody. Flow cytometry HMGB1 In this study, we examined the role of Ig and Ek enhancers in enhancing SHM in the episomal vector pCEP4 that expresses an anti-high mobility group box 1 (HMGB1) full-length antibody. 31536603 chr22 43148768 43150768 TSPO The 18- kDa translocator protein TSPO is used as an imaging target in positron emission tomogra_x0002_phy to detect neuroinflammation, and its expression is correlated with microglial activation human Nervous High+Lowthroughput Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2 否 Neuroinflammation microglial cell E_02_0211 PCR, Western blot, immunofluorescence staining The 18- kDa translocator protein TSPO is used as an imaging target in positron emission tomogra_x0002_phy to detect neuroinflammation, and its expression is correlated with microglial activation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The 18- kDa translocator protein TSPO is used as an imaging target in positron emission tomogra_x0002_phy to detect neuroinflammation, and its expression is correlated with microglial activation Immunohistochemical staining The 18- kDa translocator protein TSPO is used as an imaging target in positron emission tomogra_x0002_phy to detect neuroinflammation, and its expression is correlated with microglial activation PCR,Western blot,免疫荧光染色 TSPO,HDAC1 The 18- kDa translocator protein TSPO is used as an imaging target in positron emission tomogra_x0002_phy to detect neuroinflammation, and its expression is correlated with microglial activation;In addition, the binding of histone deacetylase 1 (HDAC1) to the enhancer region, which contains the AP-1 site, was decreased by LPS treatment, but there were no significant differences in HDAC1 binding to the proximal promoter region with or without LPS. 31535083 chr6 90460328 90462328 Aldh1l1 We performed RNA-seq both on GFP+ and GFP− sorted nuclei in all physiological conditions tested. The specificity of our nuclei isolation protocol was validated by the high level of enrichment of Lepr and by the strong depletion of genes spe_x0002_cifically expressed in oligodendrocytes (Mag), microglia (Cx3cr1) and astrocytes (Aldh1l1) (Fig. 2a). mouse Epithelial High+Lowthroughput Genomic and epigenomic mapping of leptin-responsive neuronal populations involved in body weight regulation 是 rs11804091 Obesity endothelial cell E_02_0212 Immunofluorescence staining, chip, flow cytometry We performed RNA-seq both on GFP+ and GFP− sorted nuclei in all physiological conditions tested. The specificity of our nuclei isolation protocol was validated by the high level of enrichment of Lepr and by the strong depletion of genes spe_x0002_cifically expressed in oligodendrocytes (Mag), microglia (Cx3cr1) and astrocytes (Aldh1l1) (Fig. 2a). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We performed RNA-seq both on GFP+ and GFP− sorted nuclei in all physiological conditions tested. The specificity of our nuclei isolation protocol was validated by the high level of enrichment of Lepr and by the strong depletion of genes spe_x0002_cifically expressed in oligodendrocytes (Mag), microglia (Cx3cr1) and astrocytes (Aldh1l1) (Fig. 2a). Immunohistochemical staining We performed RNA-seq both on GFP+ and GFP− sorted nuclei in all physiological conditions tested. The specificity of our nuclei isolation protocol was validated by the high level of enrichment of Lepr and by the strong depletion of genes spe_x0002_cifically expressed in oligodendrocytes (Mag), microglia (Cx3cr1) and astrocytes (Aldh1l1) (Fig. 2a). 免疫荧光染色,CHIP,Flow cytometry Aldh1l1,Cx3cr1 We performed RNA-seq both on GFP+ and GFP− sorted nuclei in all physiological conditions tested. The specificity of our nuclei isolation protocol was validated by the high level of enrichment of Lepr and by the strong depletion of genes spe_x0002_cifically expressed in oligodendrocytes (Mag), microglia (Cx3cr1) and astrocytes (Aldh1l1) (Fig. 2a).;We performed RNA-seq both on GFP+ and GFP− sorted nuclei in all physiological conditions tested. The specificity of our nuclei isolation protocol was validated by the high level of enrichment of Lepr and by the strong depletion of genes spe_x0002_cifically expressed in oligodendrocytes (Mag), microglia (Cx3cr1) and astrocytes (Aldh1l1) (Fig. 2a). 31530015 chr16 23577727 23579727 NDUFAB1 A dramatic decrease of NDUFAB1 protein was detected in the skeletal muscle of both db/db diabetic mice (Fig. 2A) and HFD-induced insulin resistance mice (Fig. 2B), amid myriads of other changes, such as elevated serum glucose levels, and altered insulin signaling and gene expression (22, 23). human connective High+Lowthroughput NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism 否 insulin resistance murine embryonic stem (ES) cell E_02_0213 PCR,Western blot A dramatic decrease of NDUFAB1 protein was detected in the skeletal muscle of both db/db diabetic mice (Fig. 2A) and HFD-induced insulin resistance mice (Fig. 2B), amid myriads of other changes, such as elevated serum glucose levels, and altered insulin signaling and gene expression (22, 23). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A dramatic decrease of NDUFAB1 protein was detected in the skeletal muscle of both db/db diabetic mice (Fig. 2A) and HFD-induced insulin resistance mice (Fig. 2B), amid myriads of other changes, such as elevated serum glucose levels, and altered insulin signaling and gene expression (22, 23). Immunohistochemical staining A dramatic decrease of NDUFAB1 protein was detected in the skeletal muscle of both db/db diabetic mice (Fig. 2A) and HFD-induced insulin resistance mice (Fig. 2B), amid myriads of other changes, such as elevated serum glucose levels, and altered insulin signaling and gene expression (22, 23). PCR,Western blot NDUFAB1 A dramatic decrease of NDUFAB1 protein was detected in the skeletal muscle of both db/db diabetic mice (Fig. 2A) and HFD-induced insulin resistance mice (Fig. 2B), amid myriads of other changes, such as elevated serum glucose levels, and altered insulin signaling and gene expression (22, 23). 31521109 chr11 58037956 58039956 VN2R9P For the human genome, cluster34 (chr11:54591480– 59,749,574) is the richest cluster of the olfactome 1 Mb cutoff list; it harbors a single VR pseudogene (VN2R9P) in between OR genes. Cluster15 (chr6:131700469–132, 646,003) of the same list is the TAAR locus, which starts with a single, otherwise remarkably isolated (39 Mb) OR gene: OR2A4 [25] human blood High+Lowthroughput A purely bioinformatic pipeline for the prediction of mammalian odorant receptor gene enhancers 否 T cell E_02_0214 PCR For the human genome, cluster34 (chr11:54591480– 59,749,574) is the richest cluster of the olfactome 1 Mb cutoff list; it harbors a single VR pseudogene (VN2R9P) in between OR genes. Cluster15 (chr6:131700469–132, 646,003) of the same list is the TAAR locus, which starts with a single, otherwise remarkably isolated (39 Mb) OR gene: OR2A4 [25] Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For the human genome, cluster34 (chr11:54591480– 59,749,574) is the richest cluster of the olfactome 1 Mb cutoff list; it harbors a single VR pseudogene (VN2R9P) in between OR genes. Cluster15 (chr6:131700469–132, 646,003) of the same list is the TAAR locus, which starts with a single, otherwise remarkably isolated (39 Mb) OR gene: OR2A4 [25] Immunohistochemical staining For the human genome, cluster34 (chr11:54591480– 59,749,574) is the richest cluster of the olfactome 1 Mb cutoff list; it harbors a single VR pseudogene (VN2R9P) in between OR genes. Cluster15 (chr6:131700469–132, 646,003) of the same list is the TAAR locus, which starts with a single, otherwise remarkably isolated (39 Mb) OR gene: OR2A4 [25] PCR VN2R9P For the human genome, cluster34 (chr11:54591480– 59,749,574) is the richest cluster of the olfactome 1 Mb cutoff list; it harbors a single VR pseudogene (VN2R9P) in between OR genes. Cluster15 (chr6:131700469–132, 646,003) of the same list is the TAAR locus, which starts with a single, otherwise remarkably isolated (39 Mb) OR gene: OR2A4 [25] 31520529 chr1 156461014 156463014 MEF2D Mt2Ddn bound strongly to the ND6-MEF2 site and disrupted the function of normal mitochondrial MEF2D without affecting the expression of the nuclear MEF2 reporter (She et al. 2011). human Nervous High+Lowthroughput Salidroside protects dopaminergic neurons by regulating the mitochondrial MEF2D-ND6 pathway in the MPTP/MPP(+) -induced model of Parkinson's disease 是 Parkinson SN4741 cells E_02_0215 PCR, immunofluorescence staining, Western blot Mt2Ddn bound strongly to the ND6-MEF2 site and disrupted the function of normal mitochondrial MEF2D without affecting the expression of the nuclear MEF2 reporter (She et al. 2011). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mt2Ddn bound strongly to the ND6-MEF2 site and disrupted the function of normal mitochondrial MEF2D without affecting the expression of the nuclear MEF2 reporter (She et al. 2011). Immunohistochemical staining Mt2Ddn bound strongly to the ND6-MEF2 site and disrupted the function of normal mitochondrial MEF2D without affecting the expression of the nuclear MEF2 reporter (She et al. 2011). PCR,免疫荧光染色,Western blot MEF2D Mt2Ddn bound strongly to the ND6-MEF2 site and disrupted the function of normal mitochondrial MEF2D without affecting the expression of the nuclear MEF2 reporter (She et al. 2011). 31519704 chr9 136491964 136493964 NOTCH1 MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. human blood High+Lowthroughput GATA3-Controlled Nucleosome Eviction Drives MYC Enhancer Activity in T-cell Development and Leukemia 否 leukemia T cell E_02_0216 PCR,Flow cytometry MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. Immunohistochemical staining MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. PCR,Flow cytometry NOTCH1,MYC MYC is a major effector of NOTCH1 oncogenic programs in T-ALL.;MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. 31519520 chr16 67560000 67562000 CTCF Sequence constraint was even higher when considering DI bins either bound by CTCF (DI_CTCF) or MYOD (DI_MYOD) or co-bound by these two TFs (DI_MYOD_CTCF) (Figure S5A). human connective High+Lowthroughput Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation 否 somatic cell E_02_0217 PCR, Western blot, flow cytometry, immunofluorescence staining Sequence constraint was even higher when considering DI bins either bound by CTCF (DI_CTCF) or MYOD (DI_MYOD) or co-bound by these two TFs (DI_MYOD_CTCF) (Figure S5A). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Sequence constraint was even higher when considering DI bins either bound by CTCF (DI_CTCF) or MYOD (DI_MYOD) or co-bound by these two TFs (DI_MYOD_CTCF) (Figure S5A). Immunohistochemical staining Sequence constraint was even higher when considering DI bins either bound by CTCF (DI_CTCF) or MYOD (DI_MYOD) or co-bound by these two TFs (DI_MYOD_CTCF) (Figure S5A). PCR,Western blot,Flow cytometry,免疫荧光染色 CTCF,ITGA7,TNNT2 Sequence constraint was even higher when considering DI bins either bound by CTCF (DI_CTCF) or MYOD (DI_MYOD) or co-bound by these two TFs (DI_MYOD_CTCF) (Figure S5A).;Upon ectopic expression, MYOD bound the promoter of ITGA7 and RDH5 at CTCF-bound elements in IMR90 (Figure 4L) and this coincided with increased interaction between the two CTCF-bound re_x0002_gions, as measured by Hi-C (Figures 4K and 4L) and validated by 3C (Figure 4L, bottom right). Importantly, these events corre_x0002_lated with an increased expression of both ITGA7 and RDH5 (Figure 4L, bottom left).;Upon MYOD induction in fibroblasts and its binding to TNNT2 promoter, we observed an increase in TNNT2 pro_x0002_moter-enhancer interaction together with an increase in TNNT2 expression (Figures 5D–5F). 31518916 chr7 148804819 148806819 EZH2 The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. human connective High+Lowthroughput Novel pharmacological inhibition of EZH2 attenuates septic shock by altering innate inflammatory responses to sepsis 否 Sepsis Inflammatory cell E_02_0218 PCR, Western blot, flow cytometry, immunofluorescence staining The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. Immunohistochemical staining The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. PCR,Western blot,Flow cytometry,免疫荧光染色 EZH2,STAT3,SOCS3,STAT1 The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown.;Blockage of EZH2 also suppressed the progression of lung injury and alleviated in_x0002_flammation by decreasing the pulmonary cell apoptosis, reducing inflammatory cells infiltration and cytokines release through inhibition of the STAT3 signaling pathway and recovery of PPARγ activation. I;In addition, EZH2 inhibitor blunted macrophage M1 polarization by SOCS3/STAT1 pathway. Overall, these data suggest that EZH2 could be a potential biomarker predicting clinical outcome and a new target for therapeutic interference in sepsis.;In addition, EZH2 inhibitor blunted macrophage M1 polarization by SOCS3/STAT1 pathway. Overall, these data suggest that EZH2 could be a potential biomarker predicting clinical outcome and a new target for therapeutic interference in sepsis. 31517633 chr19 2246854 2248854 AMH Hormonal disturbances, including increased level of androgens, estradiol, AMH and lower level of progesterone, also are one of etiologies related to PCOS (Patel 2018). human stomach High+Lowthroughput Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats 否 Gastric adenocarcinoma, polycystic ovary syndrome gastric adenocarcinoma cell E_02_0219 PCR Hormonal disturbances, including increased level of androgens, estradiol, AMH and lower level of progesterone, also are one of etiologies related to PCOS (Patel 2018). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hormonal disturbances, including increased level of androgens, estradiol, AMH and lower level of progesterone, also are one of etiologies related to PCOS (Patel 2018). Immunohistochemical staining Hormonal disturbances, including increased level of androgens, estradiol, AMH and lower level of progesterone, also are one of etiologies related to PCOS (Patel 2018). PCR AMH Hormonal disturbances, including increased level of androgens, estradiol, AMH and lower level of progesterone, also are one of etiologies related to PCOS (Patel 2018). 31515577 chr19 4966088 4968088 KDM4B Depletion of KDM4B or KDM6B favored adipogenic dif_x0002_ferentiation at the expense of osteogenic differentiation. human bone High+Lowthroughput Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling 否 osteoporosis Bone marrow stromal cell E_02_0220 PCR,Western blot Depletion of KDM4B or KDM6B favored adipogenic dif_x0002_ferentiation at the expense of osteogenic differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Depletion of KDM4B or KDM6B favored adipogenic dif_x0002_ferentiation at the expense of osteogenic differentiation. Immunohistochemical staining Depletion of KDM4B or KDM6B favored adipogenic dif_x0002_ferentiation at the expense of osteogenic differentiation. PCR,Western blot KDM4B,KDM6B,SOX9 Depletion of KDM4B or KDM6B favored adipogenic dif_x0002_ferentiation at the expense of osteogenic differentiation.;Depletion of KDM4B or KDM6B favored adipogenic dif_x0002_ferentiation at the expense of osteogenic differentiation.;KDM4B also promotes chondrogenic differentiation of human MSCs due to its recruitment to the chondrogenic gene SOX9 promoter, removing the silencing H3K9me3 marks, and thus activat_x0002_ing the transcription of SOX9 [14]. 31513343 chr17 42310771 42312771 STAT3 Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. human connective High+Lowthroughput Generation of Nanog reporter mice that distinguish pluripotent stem cells from unipotent primordial germ cells 否 pluripotent stem cell E_02_0221 PCR, flow cytometry, immunofluorescence staining Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. Immunohistochemical staining Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. PCR,Flow cytometry,免疫荧光染色 STAT3 Nanog is also regulated by the binding of STAT3 (Suzuki et al., 2006a), T (also known as Brachyury) (Suzuki et al., 2006a), and Sall4/ Nanog complex (Wu et al., 2006) at −4.9 kb region. Although the reg_x0002_ulation of Nanog expression by these transcription factors has been elucidated using the reporter assays in vitro, in vivo tissue specificity has not been demonstrated by using the standard Nanog reporter Tg mouse lines. 31511694 chr21 45491095 45493095 SLC19A1 SLC19A1 was one of the most significant hits in both screens. SLC19A1 is a folate–organic phosphate antiporter that transports folates, structurally similar antifolates and a variety of organic phos_x0002_phates encompassing (among others) thiamine derivatives and nucle_x0002_otides15,16. human blood High+Lowthroughput SLC19A1 transports immunoreactive cyclic dinucleotides 否 leukemia B cell E_02_0222 Western blot,PCR,Flow cytometry SLC19A1 was one of the most significant hits in both screens. SLC19A1 is a folate–organic phosphate antiporter that transports folates, structurally similar antifolates and a variety of organic phos_x0002_phates encompassing (among others) thiamine derivatives and nucle_x0002_otides15,16. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SLC19A1 was one of the most significant hits in both screens. SLC19A1 is a folate–organic phosphate antiporter that transports folates, structurally similar antifolates and a variety of organic phos_x0002_phates encompassing (among others) thiamine derivatives and nucle_x0002_otides15,16. Immunohistochemical staining SLC19A1 was one of the most significant hits in both screens. SLC19A1 is a folate–organic phosphate antiporter that transports folates, structurally similar antifolates and a variety of organic phos_x0002_phates encompassing (among others) thiamine derivatives and nucle_x0002_otides15,16. Western blot,PCR,Flow cytometry SLC19A1,CCL5,IRF3 SLC19A1 was one of the most significant hits in both screens. SLC19A1 is a folate–organic phosphate antiporter that transports folates, structurally similar antifolates and a variety of organic phos_x0002_phates encompassing (among others) thiamine derivatives and nucle_x0002_otides15,16.;SLC19A1 depletion—similar to depletion of IRF3 or STING—also inhibited CDN-induced expression of direct downstream target genes in the STING pathway, including IFNB1 and the chemokine genes CCL5 and CXCL1021,22 (Fig. 2c, Extended Data Fig. 3g–i).;Protein levels of STING, TBK1 and IRF3 were unaltered in SLC19A1- depleted cells 31511524 chr20 43664495 43666495 MYBL2 Strikingly, targeting this GGAA-microsatellite by clustered regularly interspaced short palindromic repeats inter_x0002_ference (CRISPRi)26–28 in highly MYBL2 expressing RDES cells strongly suppressed MYBL2 transcription (Fig. 1f) and induced a potentially counter-regulatory upregulation of EWSR1-FLI1 (Sup_x0002_plementary Fig. 1i). I human connective High+Lowthroughput Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes 否 Malignancy E_02_0223 Flow cytometry,Western blot Strikingly, targeting this GGAA-microsatellite by clustered regularly interspaced short palindromic repeats inter_x0002_ference (CRISPRi)26–28 in highly MYBL2 expressing RDES cells strongly suppressed MYBL2 transcription (Fig. 1f) and induced a potentially counter-regulatory upregulation of EWSR1-FLI1 (Sup_x0002_plementary Fig. 1i). I Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Strikingly, targeting this GGAA-microsatellite by clustered regularly interspaced short palindromic repeats inter_x0002_ference (CRISPRi)26–28 in highly MYBL2 expressing RDES cells strongly suppressed MYBL2 transcription (Fig. 1f) and induced a potentially counter-regulatory upregulation of EWSR1-FLI1 (Sup_x0002_plementary Fig. 1i). I Immunohistochemical staining Strikingly, targeting this GGAA-microsatellite by clustered regularly interspaced short palindromic repeats inter_x0002_ference (CRISPRi)26–28 in highly MYBL2 expressing RDES cells strongly suppressed MYBL2 transcription (Fig. 1f) and induced a potentially counter-regulatory upregulation of EWSR1-FLI1 (Sup_x0002_plementary Fig. 1i). I Flow cytometry,Western blot MYBL2,CDK2 Strikingly, targeting this GGAA-microsatellite by clustered regularly interspaced short palindromic repeats inter_x0002_ference (CRISPRi)26–28 in highly MYBL2 expressing RDES cells strongly suppressed MYBL2 transcription (Fig. 1f) and induced a potentially counter-regulatory upregulation of EWSR1-FLI1 (Sup_x0002_plementary Fig. 1i). I;High MYBL2 levels sensitize EwS cells for inhibition of its upstream activating kinase CDK2 in vitro and in vivo, suggesting MYBL2 as a putative biomarker for anti-CDK2-therapy. 31511494 chr7 148804549 148806549 EZH2 Here we found that Pb exposure diminished H3K27me3 levels in vivo by suppressing EZH2 (enhancer of zeste homolog 2) expression at an early stage. human connective High+Lowthroughput Interplay of miR-137 and EZH2 contributes to the genome-wide redistribution of H3K27me3 underlying the Pb-induced memory impairment 否 Multiple neurodegenerative diseases PC 12 cell E_02_0224 PCR, Western blot, immunofluorescence staining Here we found that Pb exposure diminished H3K27me3 levels in vivo by suppressing EZH2 (enhancer of zeste homolog 2) expression at an early stage. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we found that Pb exposure diminished H3K27me3 levels in vivo by suppressing EZH2 (enhancer of zeste homolog 2) expression at an early stage. Immunohistochemical staining Here we found that Pb exposure diminished H3K27me3 levels in vivo by suppressing EZH2 (enhancer of zeste homolog 2) expression at an early stage. PCR,Western blot,免疫荧光染色 EZH2 Here we found that Pb exposure diminished H3K27me3 levels in vivo by suppressing EZH2 (enhancer of zeste homolog 2) expression at an early stage. 31511252 chr5 29675484 29677484 Mnx1 Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development – except where enhancers are deleted – and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. mouse connective High+Lowthroughput Developmentally regulated Shh expression is robust to TAD perturbations 否 embryonic stem cell E_02_0225 PCR,Flow cytometry Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development – except where enhancers are deleted – and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development – except where enhancers are deleted – and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. Immunohistochemical staining Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development – except where enhancers are deleted – and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. PCR,Flow cytometry Mnx1,CTCF Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development – except where enhancers are deleted – and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD.;Interprobe distances between all three probe pairs were significantly increased in CTCF deletion cells compared with wild-type ESCs (Fig. 3E; Table S2), consistent with the reduced interactions between Shh and 31509011 chr12 9617434 9619434 Osr1 Other transcription factors such as Osr1, Eya1, Sall1 and Cited1 also play critical roles in nephron progenitors during kidney development (39, 66, 74, 91, 92). mouse kidney High+Lowthroughput In utero exposure to maternal diabetes impairs nephron progenitor differentiation 否 diabetes nephron progenitor cell E_02_0226 Western blot, immunofluorescence staining, flow cytometry Other transcription factors such as Osr1, Eya1, Sall1 and Cited1 also play critical roles in nephron progenitors during kidney development (39, 66, 74, 91, 92). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Other transcription factors such as Osr1, Eya1, Sall1 and Cited1 also play critical roles in nephron progenitors during kidney development (39, 66, 74, 91, 92). Immunohistochemical staining Other transcription factors such as Osr1, Eya1, Sall1 and Cited1 also play critical roles in nephron progenitors during kidney development (39, 66, 74, 91, 92). Western blot,免疫荧光染色, Flow cytometry Osr1 Other transcription factors such as Osr1, Eya1, Sall1 and Cited1 also play critical roles in nephron progenitors during kidney development (39, 66, 74, 91, 92). 31489250 chr7 142201541 142203541 Igf2 gf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. mouse Musculature High+Lowthroughput Paternal bias expression of Igf2as is enhancer-dependent on the imprinting cluster of Igf2, H19 and Nctc1 in muscle cells 是 muscle cell E_02_0227 Western blot, PCR, immunofluorescence staining gf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq gf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. Immunohistochemical staining gf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. Western blot,PCR,免疫荧光染色 Igf2 gf2, H19, and Nctc1 are linked co-regulated genes on distal mouse chromosome 7. 31487061 chr7 148803986 148805986 EZH2 EZH2 plays an important role in bone homeostasis and the use of the small molecule inhibitor GSK126 (a potent and highly selective EZH2 methyltransferase inhibitor(22)) exhibited promising bone protecting effects in several osteoporotic/inflam_x0002_matory and malignant osteolytic bone pathologies.(23–27) human connective High+Lowthroughput EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets 否 stem cell E_02_0228 Western blot, PCR, immunofluorescence staining EZH2 plays an important role in bone homeostasis and the use of the small molecule inhibitor GSK126 (a potent and highly selective EZH2 methyltransferase inhibitor(22)) exhibited promising bone protecting effects in several osteoporotic/inflam_x0002_matory and malignant osteolytic bone pathologies.(23–27) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 plays an important role in bone homeostasis and the use of the small molecule inhibitor GSK126 (a potent and highly selective EZH2 methyltransferase inhibitor(22)) exhibited promising bone protecting effects in several osteoporotic/inflam_x0002_matory and malignant osteolytic bone pathologies.(23–27) Immunohistochemical staining EZH2 plays an important role in bone homeostasis and the use of the small molecule inhibitor GSK126 (a potent and highly selective EZH2 methyltransferase inhibitor(22)) exhibited promising bone protecting effects in several osteoporotic/inflam_x0002_matory and malignant osteolytic bone pathologies.(23–27) Western blot,PCR,免疫荧光染色 EZH2 EZH2 plays an important role in bone homeostasis and the use of the small molecule inhibitor GSK126 (a potent and highly selective EZH2 methyltransferase inhibitor(22)) exhibited promising bone protecting effects in several osteoporotic/inflam_x0002_matory and malignant osteolytic bone pathologies.(23–27) 31481796 chr7 148804478 148806478 EZH2 Typical genomic dis_x0002_tributions of Pol II, EZH2 and H3K27me3 were also identified in our data (Supplementary Fig. 3d,h; Fig. 2h). human Epithelial High+Lowthroughput Profiling chromatin states using single-cell itChIP-seq 否 endothelial cell E_02_0229 Flow cytometry Typical genomic dis_x0002_tributions of Pol II, EZH2 and H3K27me3 were also identified in our data (Supplementary Fig. 3d,h; Fig. 2h). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Typical genomic dis_x0002_tributions of Pol II, EZH2 and H3K27me3 were also identified in our data (Supplementary Fig. 3d,h; Fig. 2h). Immunohistochemical staining Typical genomic dis_x0002_tributions of Pol II, EZH2 and H3K27me3 were also identified in our data (Supplementary Fig. 3d,h; Fig. 2h). Flow cytometry EZH2 Typical genomic dis_x0002_tributions of Pol II, EZH2 and H3K27me3 were also identified in our data (Supplementary Fig. 3d,h; Fig. 2h). 31481496 chr17 42310597 42312597 STAT3 Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, includ_x0002_ing gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcrip_x0002_tional activity. human stomach High+Lowthroughput Serine-Phosphorylated STAT3 Promotes Tumorigenesis via Modulation of RNA Polymerase Transcriptional Activity 否 gastric cancer gastric cancer cell E_02_0230 Western blot,PCR Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, includ_x0002_ing gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcrip_x0002_tional activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, includ_x0002_ing gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcrip_x0002_tional activity. Immunohistochemical staining Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, includ_x0002_ing gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcrip_x0002_tional activity. Western blot,PCR STAT3 Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, includ_x0002_ing gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcrip_x0002_tional activity. 31477927 chr3 101825274 101827274 NFKBIZ We checked typical examples of the short- and long-lived mRNAs NFKBIZ35 and GAPDH, respectively, in MCF-7 cells. The signal from NFKBIZ (Figs. 2a and 3a,b) was higher in NET_x0002_CAGE than in CAGE, whereas the opposite was true for GAPDH (Figs. 2a and 3b). human breast High+Lowthroughput NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements 否 mammary cancer breast cancer cell E_02_0231 PCR,Flow cytometry We checked typical examples of the short- and long-lived mRNAs NFKBIZ35 and GAPDH, respectively, in MCF-7 cells. The signal from NFKBIZ (Figs. 2a and 3a,b) was higher in NET_x0002_CAGE than in CAGE, whereas the opposite was true for GAPDH (Figs. 2a and 3b). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We checked typical examples of the short- and long-lived mRNAs NFKBIZ35 and GAPDH, respectively, in MCF-7 cells. The signal from NFKBIZ (Figs. 2a and 3a,b) was higher in NET_x0002_CAGE than in CAGE, whereas the opposite was true for GAPDH (Figs. 2a and 3b). Immunohistochemical staining We checked typical examples of the short- and long-lived mRNAs NFKBIZ35 and GAPDH, respectively, in MCF-7 cells. The signal from NFKBIZ (Figs. 2a and 3a,b) was higher in NET_x0002_CAGE than in CAGE, whereas the opposite was true for GAPDH (Figs. 2a and 3b). PCR,Flow cytometry NFKBIZ,GAPDH We checked typical examples of the short- and long-lived mRNAs NFKBIZ35 and GAPDH, respectively, in MCF-7 cells. The signal from NFKBIZ (Figs. 2a and 3a,b) was higher in NET_x0002_CAGE than in CAGE, whereas the opposite was true for GAPDH (Figs. 2a and 3b).;We checked typical examples of the short- and long-lived mRNAs NFKBIZ35 and GAPDH, respectively, in MCF-7 cells. The signal from NFKBIZ (Figs. 2a and 3a,b) was higher in NET_x0002_CAGE than in CAGE, whereas the opposite was true for GAPDH (Figs. 2a and 3b). 30700527 chr4 109910195 109912195 EGF Genetic screens in the nematode Caenorhabditis elegans identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. human epithelial High+Lowthroughput Necessity and Contingency in Developmental Genetic Screens: EGF, Wnt, and Semaphorin Pathways in Vulval Induction of the Nematode Oscheius tipulae 否 precursor cell E_02_0232 PCR, sequencing technology, neighbor joining method Genetic screens in the nematode Caenorhabditis elegans identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genetic screens in the nematode Caenorhabditis elegans identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. Immunohistochemical staining Genetic screens in the nematode Caenorhabditis elegans identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. PCR,测序技术,neighbor-joining method EGF Genetic screens in the nematode Caenorhabditis elegans identified the EGF/Ras and Notch pathways as central for vulval precursor cell fate patterning. 30700190 chr9 117701691 117703691 TLR4 Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. human pancreas High+Lowthroughput Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier 否 Acute severe pancreatitis pancreatic acinar cells E_02_0233 Western blotting, Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. Immunohistochemical staining Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. Western blotting, TLR4 Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. 30699347 chrX 72326894 72328894 HDAC8 By contrast, our results indicate that recruiting dCas9-HDAC8 (-ac) to Fos Enh2 predominantly reduces the ON rate relative to control-transfected neurons. human nerve High+Lowthroughput Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes 否 E_02_0234 FISH By contrast, our results indicate that recruiting dCas9-HDAC8 (-ac) to Fos Enh2 predominantly reduces the ON rate relative to control-transfected neurons. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By contrast, our results indicate that recruiting dCas9-HDAC8 (-ac) to Fos Enh2 predominantly reduces the ON rate relative to control-transfected neurons. Immunohistochemical staining By contrast, our results indicate that recruiting dCas9-HDAC8 (-ac) to Fos Enh2 predominantly reduces the ON rate relative to control-transfected neurons. FISH HDAC8 By contrast, our results indicate that recruiting dCas9-HDAC8 (-ac) to Fos Enh2 predominantly reduces the ON rate relative to control-transfected neurons. 30699336 chr17 80098759 80100759 GAA The surface decoration of CPNL was performed by adding Transcutol which act as a nonionic penetration enhancer. Accurately weighed 100 mg of Capecitabine and 0.4% w/v of Chitosan were dissolved in 1% v/v aqueous glacial acetic acid (GAA) solution. human skin High+Lowthroughput pH triggered and charge attracted nanogel for simultaneous evaluation of penetration and toxicity against skin cancer: In-vitro and ex-vivo study 否 Skin cancer E_02_0235 Ionotropic gelation technique, The surface decoration of CPNL was performed by adding Transcutol which act as a nonionic penetration enhancer. Accurately weighed 100 mg of Capecitabine and 0.4% w/v of Chitosan were dissolved in 1% v/v aqueous glacial acetic acid (GAA) solution. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The surface decoration of CPNL was performed by adding Transcutol which act as a nonionic penetration enhancer. Accurately weighed 100 mg of Capecitabine and 0.4% w/v of Chitosan were dissolved in 1% v/v aqueous glacial acetic acid (GAA) solution. Immunohistochemical staining The surface decoration of CPNL was performed by adding Transcutol which act as a nonionic penetration enhancer. Accurately weighed 100 mg of Capecitabine and 0.4% w/v of Chitosan were dissolved in 1% v/v aqueous glacial acetic acid (GAA) solution. Ionotropic gelation technique, GAA The surface decoration of CPNL was performed by adding Transcutol which act as a nonionic penetration enhancer. Accurately weighed 100 mg of Capecitabine and 0.4% w/v of Chitosan were dissolved in 1% v/v aqueous glacial acetic acid (GAA) solution. 30696265 chr2 136111778 136113778 CXCR4 These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell-primed splenic Treg cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting Treg cell function in vivo. human lymph High+Lowthroughput C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function 否 miocardial infarction T cell E_02_0236 FISH These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell-primed splenic Treg cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting Treg cell function in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell-primed splenic Treg cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting Treg cell function in vivo. Immunohistochemical staining These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell-primed splenic Treg cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting Treg cell function in vivo. FISH CXCR4 These data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell-primed splenic Treg cells as the central arbiters of these therapeutic effects and thereby delineate a pharmacological strategy to promote infarct repair by augmenting Treg cell function in vivo. 30692641 chrX 44870388 44872388 KDM6A We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. human muscle High+Lowthroughput Inhibition of EZH2 induces NK cell-mediated differentiation and death in?muscle-invasive bladder cancer 否 Muscle invasive bladder cancer E_02_0237 PCR, Western blots, sequencing technology We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. Immunohistochemical staining We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. PCR，Western blots,测序技术 KDM6A We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. 30691060 chr4 74742012 74744012 BTC The dried powders of CIVT and CIEE were stored at 4 °C until use. CIVT was provided from BTC corporation human fat High+Lowthroughput Effect of Enzymatic Treatment of Chrysanthemum indicum Linné Extracts on Lipid Accumulation and Adipogenesis in High-Fat-Diet-Induced Obese Male Mice 否 Hyperostosis mesenchymal precursor cell E_02_0238 Western Blot,ELISA,HPLC,Micro-CT The dried powders of CIVT and CIEE were stored at 4 °C until use. CIVT was provided from BTC corporation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The dried powders of CIVT and CIEE were stored at 4 °C until use. CIVT was provided from BTC corporation Immunohistochemical staining The dried powders of CIVT and CIEE were stored at 4 °C until use. CIVT was provided from BTC corporation Western Blot,ELISA,HPLC,Micro-CT BTC The dried powders of CIVT and CIEE were stored at 4 °C until use. CIVT was provided from BTC corporation 30687302 chr16 67559454 67561454 CTCF RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated, respectively, in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF) human lung High+Lowthroughput Enhancer Associated Long Non-coding RNA Transcription and Gene Regulation in Experimental Models of Rickettsial Infection Human spotted fever rickettsial disease endothelial cell E_02_0239 PCR，ChIP-Seq RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated, respectively, in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated, respectively, in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF) Immunohistochemical staining RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated, respectively, in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF) PCR，ChIP-Seq CTCF RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated, respectively, in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF) 30686579 chr3 133743493 133745493 TF Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility human lymph High+Lowthroughput The cis-Regulatory Atlas of the Mouse Immune System immune cell E_02_0240 PCR，ChIP-seq Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility Immunohistochemical staining Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility PCR，ChIP-seq TF Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility 30680334 chr12 109416349 109418349 Dlk1 The highest level of Dlk1 transcript was found at 7 days of age, followed by significant and steady drops of the transcript level until 44 days of age mouse epididymis High+Lowthroughput Expressional Patterns of Adipocyte-Associated Molecules in the Rat Epididymal Fat during Postnatal Development Period fat cell E_02_0241 PCR, Western blot, sequencing technology The highest level of Dlk1 transcript was found at 7 days of age, followed by significant and steady drops of the transcript level until 44 days of age Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The highest level of Dlk1 transcript was found at 7 days of age, followed by significant and steady drops of the transcript level until 44 days of age Immunohistochemical staining The highest level of Dlk1 transcript was found at 7 days of age, followed by significant and steady drops of the transcript level until 44 days of age PCR，Western blot，测序技术 Dlk1 The highest level of Dlk1 transcript was found at 7 days of age, followed by significant and steady drops of the transcript level until 44 days of age 30671485 chr3 194133166 194135166 HES1 The effects of polarized BMDMs on the expression of hepatic progenitor cell- (HPC-) specific markers and hairy and enhancer of split-1 (HES1) in HPCs in coculture were also analyzed. human liver High+Lowthroughput M1-Polarized Macrophages Promote Self-Renewing Phenotype of Hepatic Progenitor Cells with Jagged1-Notch Signalling Involved: Relevance in Primary Sclerosing Cholangitis Primary sclerosing cholangitis macrophage E_02_0242 PCR，Western blot The effects of polarized BMDMs on the expression of hepatic progenitor cell- (HPC-) specific markers and hairy and enhancer of split-1 (HES1) in HPCs in coculture were also analyzed. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The effects of polarized BMDMs on the expression of hepatic progenitor cell- (HPC-) specific markers and hairy and enhancer of split-1 (HES1) in HPCs in coculture were also analyzed. Immunohistochemical staining The effects of polarized BMDMs on the expression of hepatic progenitor cell- (HPC-) specific markers and hairy and enhancer of split-1 (HES1) in HPCs in coculture were also analyzed. PCR，Western blot HES1 The effects of polarized BMDMs on the expression of hepatic progenitor cell- (HPC-) specific markers and hairy and enhancer of split-1 (HES1) in HPCs in coculture were also analyzed. 30669987 chr11 83550448 83552448 Ccl4 Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. mouse lymph High+Lowthroughput Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection Tuberculosis macrophage E_02_0243 ChIP-seq Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. Immunohistochemical staining Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. ChIP-seq Ccl4 Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. 30664630 chr9 99819018 99821018 NR4A3 Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. human sialaden High+Lowthroughput Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands Salivary gland acinar cell carcinoma Acinar cell of salivary gland E_02_0244 PCR，Western blot，ChIP-seq Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. Immunohistochemical staining Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. PCR，Western blot，ChIP-seq NR4A3 Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. 30660454 chr3 38135367 38137367 MYD88 Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β human lymph High+Lowthroughput Scientific validation of anti-arthritic effect of Kashayams - A polyherbal formulation in collagen induced arthritic rats arthritis B cell E_02_0245 PCR Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β Immunohistochemical staining Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β PCR MYD88 Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β 30659184 chr4 108044594 108046594 LEF1 Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). human bone High+Lowthroughput Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis Osteoarthritis hematopoietic pre-B cell E_02_0246 PCR，Western blot，ChIP-seq Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Immunohistochemical staining Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). PCR，Western blot，ChIP-seq LEF1 Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). 30655737 chr7 44101607 44103607 AEBP1 The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC) human lymph High+Lowthroughput MicroRNA 214 inhibits adipocyte enhancer-binding protein 1 activity and increases the sensitivity of chemotherapy in colorectal cancer Colorectal cancer HT-29 cell E_02_0247 Western blot, flow cytometry The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC) Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC) Immunohistochemical staining The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC) Western blot,流式细胞术 AEBP1 The present study aimed to analyze adipocyte enhancer-binding protein 1 (AEBP1) expression in colorectal cancer (CRC) 30652078 chr11 73122225 73124225 Trpv1 Trpv1 altered the cell signaling events that increase myogenic transcription factors in myoblast cells in response to heat. Trpv1 plays important roles in the process of differentiation. mouse bone High+Lowthroughput Heat induces myogenic transcription factors of myoblast cells via transient receptor potential vanilloid 1 (Trpv1) myoblast cell E_02_0248 PCR，Western blot Trpv1 altered the cell signaling events that increase myogenic transcription factors in myoblast cells in response to heat. Trpv1 plays important roles in the process of differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Trpv1 altered the cell signaling events that increase myogenic transcription factors in myoblast cells in response to heat. Trpv1 plays important roles in the process of differentiation. Immunohistochemical staining Trpv1 altered the cell signaling events that increase myogenic transcription factors in myoblast cells in response to heat. Trpv1 plays important roles in the process of differentiation. PCR，Western blot Trpv1 Trpv1 altered the cell signaling events that increase myogenic transcription factors in myoblast cells in response to heat. Trpv1 plays important roles in the process of differentiation. 30651760 chr13 30454192 30456192 HMGB1 The results of the RT-qPCR demonstrated that hypoxia stimulation increased the expression of HMGB1, PPAR, RAGE and TNF-α mRNA, and decreased the expression of SIRT1 mRNA in kidney tissues (P<0.05). human kidney High+Lowthroughput The HMGB1-RAGE/TLR-TNF-α signaling pathway may contribute to kidney injury induced by hypoxia Renal impairment B cell E_02_0249 PCR, sequencing technology The results of the RT-qPCR demonstrated that hypoxia stimulation increased the expression of HMGB1, PPAR, RAGE and TNF-α mRNA, and decreased the expression of SIRT1 mRNA in kidney tissues (P<0.05). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results of the RT-qPCR demonstrated that hypoxia stimulation increased the expression of HMGB1, PPAR, RAGE and TNF-α mRNA, and decreased the expression of SIRT1 mRNA in kidney tissues (P<0.05). Immunohistochemical staining The results of the RT-qPCR demonstrated that hypoxia stimulation increased the expression of HMGB1, PPAR, RAGE and TNF-α mRNA, and decreased the expression of SIRT1 mRNA in kidney tissues (P<0.05). PCR，测序技术 HMGB1 The results of the RT-qPCR demonstrated that hypoxia stimulation increased the expression of HMGB1, PPAR, RAGE and TNF-α mRNA, and decreased the expression of SIRT1 mRNA in kidney tissues (P<0.05). 30651277 chr15 45089423 45091423 DUOX2 This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production. human internal secretion High+Lowthroughput An exonic splicing enhancer mutation in DUOX2 causes aberrant alternative splicing and severe congenital hypothyroidism in Bama pigs Congenital hypothyroidism HeLa cell E_02_0250 PCR, Western blot, sequencing technology This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production. Immunohistochemical staining This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production. PCR，Western blot，测序技术 DUOX2 This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production. 30647808 chr20 5112515 5114515 PCNA The vetsin experimental group in this study exhibited hepatocyte deterioration, significant necrosis, and scattered growth of Kupffer cells among certain hepatocytes and around the portal area, significant blockage of blood sinusoids, and elevated hepatic expression of PCNA and P53. human Liver High+Lowthroughput Roles of Moringa oleifera Leaf Extract in Improving the Impact of High Dietary Intake of Monosodium Glutamate-Induced Liver Toxicity, Oxidative Stress, Genotoxicity, DNA Damage, and PCNA Alterations in Male Rats hepatocyte E_02_0251 Immunohistochemical detection The vetsin experimental group in this study exhibited hepatocyte deterioration, significant necrosis, and scattered growth of Kupffer cells among certain hepatocytes and around the portal area, significant blockage of blood sinusoids, and elevated hepatic expression of PCNA and P53. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The vetsin experimental group in this study exhibited hepatocyte deterioration, significant necrosis, and scattered growth of Kupffer cells among certain hepatocytes and around the portal area, significant blockage of blood sinusoids, and elevated hepatic expression of PCNA and P53. Immunohistochemical staining The vetsin experimental group in this study exhibited hepatocyte deterioration, significant necrosis, and scattered growth of Kupffer cells among certain hepatocytes and around the portal area, significant blockage of blood sinusoids, and elevated hepatic expression of PCNA and P53. 免疫组化检测 PCNA The vetsin experimental group in this study exhibited hepatocyte deterioration, significant necrosis, and scattered growth of Kupffer cells among certain hepatocytes and around the portal area, significant blockage of blood sinusoids, and elevated hepatic expression of PCNA and P53. 30643696 chr2 239045624 239047624 HDAC4 These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. human bone High+Lowthroughput hdac4 mediates perichondral ossification and pharyngeal skeleton development in the zebrafish chondroblast E_02_0252 PCR，Western blot These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. Immunohistochemical staining These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. PCR，Western blot HDAC4 These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. 30641938 chr8 84014018 84016018 Ucp1 Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. mouse adipose High+Lowthroughput Endoplasmic Reticulum Stress Impaired Uncoupling Protein 1 Expression via the Suppression of Peroxisome Proliferator-Activated Receptor γ Binding Activity in Mice Beige Adipocytes tongue cancer IWAT cell E_02_0253 PCR，Western blot，ChIP-seq Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. Immunohistochemical staining Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. PCR，Western blot，ChIP-seq Ucp1 Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. 30630822 chr4 54654587 54656587 KIT In this study, we identify regulatory regions of the KIT enhancer essential for KIT gene expression and GIST cell viability. human stomach High+Lowthroughput Enhancer Domains in Gastrointestinal Stromal Tumor Regulate KIT Expression and Are Targetable by BET Bromodomain Inhibition Gastrointestinal stromal tumors GIST cell E_02_0254 Chip SEQ, RNA SEQ, immunoblotting, cloning, CRISPR assays, PCR In this study, we identify regulatory regions of the KIT enhancer essential for KIT gene expression and GIST cell viability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we identify regulatory regions of the KIT enhancer essential for KIT gene expression and GIST cell viability. Immunohistochemical staining In this study, we identify regulatory regions of the KIT enhancer essential for KIT gene expression and GIST cell viability. ChIP-seq，RNA-seq，免疫印迹法，Cloning ，CRISPR assays，PCR KIT In this study, we identify regulatory regions of the KIT enhancer essential for KIT gene expression and GIST cell viability. 30630179 chr17 42310249 42312249 STAT3 The expression vectors for wild type (WT) STAT3 (Stat3 Flag pRC/CMV, #8707, Addgene, Cambridge), dominant negative (DN) STAT3 (Stat3 Y705F Flag pRC/CMV, #8704, Addgene, Cambridge), constitutively active (CA) STAT3 (Stat3-C Flag pRC/CMV, #8722, Addgene, Cambridge), and luciferase reporter containing STAT3 response element (SBR, 4xM67 pTATA TK-Luc, #8688, Addgene, Cambridge, MA) were purchased from Addgene and have previously been described [74]. human blood High+Lowthroughput Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice leukemia GT1–7 cell E_02_0255 Immunohistochemistry, cell transfection, PCR, Western blot The expression vectors for wild type (WT) STAT3 (Stat3 Flag pRC/CMV, #8707, Addgene, Cambridge), dominant negative (DN) STAT3 (Stat3 Y705F Flag pRC/CMV, #8704, Addgene, Cambridge), constitutively active (CA) STAT3 (Stat3-C Flag pRC/CMV, #8722, Addgene, Cambridge), and luciferase reporter containing STAT3 response element (SBR, 4xM67 pTATA TK-Luc, #8688, Addgene, Cambridge, MA) were purchased from Addgene and have previously been described [74]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression vectors for wild type (WT) STAT3 (Stat3 Flag pRC/CMV, #8707, Addgene, Cambridge), dominant negative (DN) STAT3 (Stat3 Y705F Flag pRC/CMV, #8704, Addgene, Cambridge), constitutively active (CA) STAT3 (Stat3-C Flag pRC/CMV, #8722, Addgene, Cambridge), and luciferase reporter containing STAT3 response element (SBR, 4xM67 pTATA TK-Luc, #8688, Addgene, Cambridge, MA) were purchased from Addgene and have previously been described [74]. Immunohistochemical staining The expression vectors for wild type (WT) STAT3 (Stat3 Flag pRC/CMV, #8707, Addgene, Cambridge), dominant negative (DN) STAT3 (Stat3 Y705F Flag pRC/CMV, #8704, Addgene, Cambridge), constitutively active (CA) STAT3 (Stat3-C Flag pRC/CMV, #8722, Addgene, Cambridge), and luciferase reporter containing STAT3 response element (SBR, 4xM67 pTATA TK-Luc, #8688, Addgene, Cambridge, MA) were purchased from Addgene and have previously been described [74]. 免疫组化，细胞转染，PCR，Western blot STAT3 The expression vectors for wild type (WT) STAT3 (Stat3 Flag pRC/CMV, #8707, Addgene, Cambridge), dominant negative (DN) STAT3 (Stat3 Y705F Flag pRC/CMV, #8704, Addgene, Cambridge), constitutively active (CA) STAT3 (Stat3-C Flag pRC/CMV, #8722, Addgene, Cambridge), and luciferase reporter containing STAT3 response element (SBR, 4xM67 pTATA TK-Luc, #8688, Addgene, Cambridge, MA) were purchased from Addgene and have previously been described [74]. 30627958 chr9 104778131 104780131 ABCA1 In detail, PGA1 activated the peroxisome proliferator-activated receptor-gamma (PPARγ) and ATP-binding cassette subfamily A member 1 (ABCA1) signalling pathways, promoting the efflux of cholesterol and decreasing the intracellular cholesterol levels. human nerve High+Lowthroughput Prostaglandin A1 Inhibits the Cognitive Decline of APP/PS1 Transgenic Mice via PPARγ/ABCA1-dependent Cholesterol Efflux Mechanisms Chronic neurodegenerative diseases microglial cell E_02_0256 Immunohistochemistry staining, PCR, Western blot, immunofluorescence In detail, PGA1 activated the peroxisome proliferator-activated receptor-gamma (PPARγ) and ATP-binding cassette subfamily A member 1 (ABCA1) signalling pathways, promoting the efflux of cholesterol and decreasing the intracellular cholesterol levels. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In detail, PGA1 activated the peroxisome proliferator-activated receptor-gamma (PPARγ) and ATP-binding cassette subfamily A member 1 (ABCA1) signalling pathways, promoting the efflux of cholesterol and decreasing the intracellular cholesterol levels. Immunohistochemical staining In detail, PGA1 activated the peroxisome proliferator-activated receptor-gamma (PPARγ) and ATP-binding cassette subfamily A member 1 (ABCA1) signalling pathways, promoting the efflux of cholesterol and decreasing the intracellular cholesterol levels. 免疫组织化学染色法，PCR，Western blot，免疫荧光法 ABCA1 In detail, PGA1 activated the peroxisome proliferator-activated receptor-gamma (PPARγ) and ATP-binding cassette subfamily A member 1 (ABCA1) signalling pathways, promoting the efflux of cholesterol and decreasing the intracellular cholesterol levels. 30626972 chr9 123999195 124001195 LHX2 The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression. human nerve High+Lowthroughput LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice E_02_0257 Hi-C，PCR，Western blot The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression. Immunohistochemical staining The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression. Hi-C，PCR，Western blot LHX2 The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression. 30626694 chr5 141617717 141619717 HDAC3 We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. human thymic High+Lowthroughput Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor-Induced Cell Death T cell E_02_0258 Flow cytometry, PCR, chip seq We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. Immunohistochemical staining We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. 流式细胞术，PCR，ChIP-seq HDAC3 We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. 30622137 chr12 106060956 106062956 NUAK1 We here report that NUAK family kinase 1 (NUAK1) and NUAK2 are two TGF target genes. NUAK1/2 belong to the AMPactivated protein kinase (AMPK) family, whose members control central and protein metabolism, polarity and overall cellular homeostasis. human myofibroblast High+Lowthroughput Transforming growth factor β (TGFβ) induces NUAK kinase expression to fine-tune its signaling output E_02_0259 Luciferase assay, fluorescence immunomicroscopy, PCR, Western blot We here report that NUAK family kinase 1 (NUAK1) and NUAK2 are two TGF target genes. NUAK1/2 belong to the AMPactivated protein kinase (AMPK) family, whose members control central and protein metabolism, polarity and overall cellular homeostasis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We here report that NUAK family kinase 1 (NUAK1) and NUAK2 are two TGF target genes. NUAK1/2 belong to the AMPactivated protein kinase (AMPK) family, whose members control central and protein metabolism, polarity and overall cellular homeostasis. Immunohistochemical staining We here report that NUAK family kinase 1 (NUAK1) and NUAK2 are two TGF target genes. NUAK1/2 belong to the AMPactivated protein kinase (AMPK) family, whose members control central and protein metabolism, polarity and overall cellular homeostasis. 荧光素酶检测，荧光免疫显微技术，PCR，Western blot NUAK1 We here report that NUAK family kinase 1 (NUAK1) and NUAK2 are two TGF target genes. NUAK1/2 belong to the AMPactivated protein kinase (AMPK) family, whose members control central and protein metabolism, polarity and overall cellular homeostasis. 30619879 chrX 147909131 147911131 FMR1 The FMR1 gene encodes the Fragile X Mental Retardation Protein, that harbors three canonical RNA-binding domains (KH1, KH2 and RGGBox) in addition to a Nuclear Localization Signal (NLS) and a Nuclear Export Signal (NES; Bardoni et al., 1997). human nerve High+Lowthroughput Fragile X Mental Retardation Protein: To Be or Not to Be a Translational Enhancer Fragile X syndrome E_02_0260 PCR The FMR1 gene encodes the Fragile X Mental Retardation Protein, that harbors three canonical RNA-binding domains (KH1, KH2 and RGGBox) in addition to a Nuclear Localization Signal (NLS) and a Nuclear Export Signal (NES; Bardoni et al., 1997). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The FMR1 gene encodes the Fragile X Mental Retardation Protein, that harbors three canonical RNA-binding domains (KH1, KH2 and RGGBox) in addition to a Nuclear Localization Signal (NLS) and a Nuclear Export Signal (NES; Bardoni et al., 1997). Immunohistochemical staining The FMR1 gene encodes the Fragile X Mental Retardation Protein, that harbors three canonical RNA-binding domains (KH1, KH2 and RGGBox) in addition to a Nuclear Localization Signal (NLS) and a Nuclear Export Signal (NES; Bardoni et al., 1997). PCR FMR1 The FMR1 gene encodes the Fragile X Mental Retardation Protein, that harbors three canonical RNA-binding domains (KH1, KH2 and RGGBox) in addition to a Nuclear Localization Signal (NLS) and a Nuclear Export Signal (NES; Bardoni et al., 1997). 30544251 chr12 35939690 35990427 GLIS1 The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic cell type-specific super-enhancers that become repressed in both lineages. human bone Low+High throughput Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulators of mesenchymal multipotency -- E_02_0261 ChIP-seq The four adjacent merged SEs (SE283,SE284,SE285,and SE286) at the Ahr locus together cover a continuous region over 300 kb of active enhancer signal downstream of the Ahr gene in the ST2 cells.Moreover, all four SEs showed a very high correlation (r ≥ 0.95) with Ahr mRNA levels as measured by RNA-seq (Figure 5C and D, upper panels) and validated by RT-qPCR. Super-Enhancer -- RT-qPCR,ChIP,RNA-seq Ah,Ahhe,In,bHLHe76,Ahr -- -- -- Ah, Ahhe, In, bHLHe76, Ahr,Gli5, Gli6, GliH1 RT-qPCR -- -- Ahr Ahr,Glis1 Ahr is regulated by multiple SEs with lineage-specific dynamics The Ahr mRNA level was measured across the differentiation by RNA-seq and RT-qPCR in both adipocyte and osteoblast differentiation and is indicated astheintactline. To confirm the observed differentiation defects in the presence of high AHR and GLIS1 levels, RT-qPCR analysis of the known adipocyte marker gene Lpl was performed. In ST2-TetOn-GFP cells Lpl was upregulated by D5 of differentiation and remained elevated in D9 cells both in presence and absence of doxycycline. 30540553 chr7 148804397 148806397 EZH2 Enhancer of zeste homolog 2 (EZH2) was expressed differentially, showing significant up-regulation in HSCs activated with TGF-β but not with PDGF-BB. human epithelial High+Lowthroughput Chemical Activation of the Ethylene Signaling Pathway Promotes Fusarium graminearum Resistance in Detached Wheat Heads Alternaria eukaryotic cell E_02_0262 Isolated head method for FHB resistance assessment Enhancer of zeste homolog 2 (EZH2) was expressed differentially, showing significant up-regulation in HSCs activated with TGF-β but not with PDGF-BB. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) was expressed differentially, showing significant up-regulation in HSCs activated with TGF-β but not with PDGF-BB. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) was expressed differentially, showing significant up-regulation in HSCs activated with TGF-β but not with PDGF-BB. FHB抗性评估的分离头法 EZH2 Enhancer of zeste homolog 2 (EZH2) was expressed differentially, showing significant up-regulation in HSCs activated with TGF-β but not with PDGF-BB. 30531963 chrX 48519108 48521108 EBP However, the mechanisms underlying the induction of this phenomenon are not fully understood. Here we report that a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1 human High+Lowthroughput Xrp1 is a transcription factor required for cell competition-driven elimination of loser cells E_02_0263 PCR，ChIP-seq However, the mechanisms underlying the induction of this phenomenon are not fully understood. Here we report that a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, the mechanisms underlying the induction of this phenomenon are not fully understood. Here we report that a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1 Immunohistochemical staining However, the mechanisms underlying the induction of this phenomenon are not fully understood. Here we report that a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1 PCR，ChIP-seq EBP However, the mechanisms underlying the induction of this phenomenon are not fully understood. Here we report that a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1 30979734 chr7 148804362 148806362 EZH2 Both gain-of-function EZH2 mutations and inactivating histone acetyltransferases mutations, such as CREBBP and EP300, have been implicated in the pathogenesis of germinal center (GC) derived lymphomas. human lymphoid High+Lowthroughput Precision Targeting with EZH2 and HDAC Inhibitors in Epigenetically Dysregulated Lymphomas 否 lymphomas E_02_0264 Flow cytometry, Western blot, RNA seq Both gain-of-function EZH2 mutations and inactivating histone acetyltransferases mutations, such as CREBBP and EP300, have been implicated in the pathogenesis of germinal center (GC) derived lymphomas. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Both gain-of-function EZH2 mutations and inactivating histone acetyltransferases mutations, such as CREBBP and EP300, have been implicated in the pathogenesis of germinal center (GC) derived lymphomas. Immunohistochemical staining Both gain-of-function EZH2 mutations and inactivating histone acetyltransferases mutations, such as CREBBP and EP300, have been implicated in the pathogenesis of germinal center (GC) derived lymphomas. 流式细胞术、Western blot、RNA-seq EZH2 Both gain-of-function EZH2 mutations and inactivating histone acetyltransferases mutations, such as CREBBP and EP300, have been implicated in the pathogenesis of germinal center (GC) derived lymphomas. 30976167 chr1 247412836 247414836 NLRP3 SF containing ginsenosides attenuates cytokine secretion by inhibiting the priming and activation steps of inflammasome activation, whereas NS induces upregulation of IL-1β precursor and nucleotide-binding and oligomerization domain (NOD)2–like receptor protein 3 (NLRP3), which are key inflammasome components, via interaction with TLR4 [4], [10]. In addition, a high dose of RGE presents a more SF predominant effect (antiinflammasome), whereas low concentration of RGE shows NS-like efficacy (proinflammasome) in macrophages [10]. human epithelial cells High+Lowthroughput Nonsaponin fraction of Korean Red Ginseng attenuates cytokine production via inhibition of TLR4 expression 否 peritonitis E_02_0265 RT-PCR、qPCR SF containing ginsenosides attenuates cytokine secretion by inhibiting the priming and activation steps of inflammasome activation, whereas NS induces upregulation of IL-1β precursor and nucleotide-binding and oligomerization domain (NOD)2–like receptor protein 3 (NLRP3), which are key inflammasome components, via interaction with TLR4 [4], [10]. In addition, a high dose of RGE presents a more SF predominant effect (antiinflammasome), whereas low concentration of RGE shows NS-like efficacy (proinflammasome) in macrophages [10]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SF containing ginsenosides attenuates cytokine secretion by inhibiting the priming and activation steps of inflammasome activation, whereas NS induces upregulation of IL-1β precursor and nucleotide-binding and oligomerization domain (NOD)2–like receptor protein 3 (NLRP3), which are key inflammasome components, via interaction with TLR4 [4], [10]. In addition, a high dose of RGE presents a more SF predominant effect (antiinflammasome), whereas low concentration of RGE shows NS-like efficacy (proinflammasome) in macrophages [10]. Immunohistochemical staining SF containing ginsenosides attenuates cytokine secretion by inhibiting the priming and activation steps of inflammasome activation, whereas NS induces upregulation of IL-1β precursor and nucleotide-binding and oligomerization domain (NOD)2–like receptor protein 3 (NLRP3), which are key inflammasome components, via interaction with TLR4 [4], [10]. In addition, a high dose of RGE presents a more SF predominant effect (antiinflammasome), whereas low concentration of RGE shows NS-like efficacy (proinflammasome) in macrophages [10]. RT-PCR、qPCR NLRP3,NLRP4 SF containing ginsenosides attenuates cytokine secretion by inhibiting the priming and activation steps of inflammasome activation, whereas NS induces upregulation of IL-1β precursor and nucleotide-binding and oligomerization domain (NOD)2–like receptor protein 3 (NLRP3), which are key inflammasome components, via interaction with TLR4 [4], [10]. In addition, a high dose of RGE presents a more SF predominant effect (antiinflammasome), whereas low concentration of RGE shows NS-like efficacy (proinflammasome) in macrophages [10].;SF containing ginsenosides attenuates cytokine secretion by inhibiting the priming and activation steps of inflammasome activation, whereas NS induces upregulation of IL-1β precursor and nucleotide-binding and oligomerization domain (NOD)3–like receptor p 30971697 chr6 45325473 45327473 RUNX2 RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. human lymphoid High+Lowthroughput Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm 否 acute leukemia E_02_0266 Immunohistochemistry, flow cytometry, DNA SEQ, RNA SEQ, RT-PCR, Western blot RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. Immunohistochemical staining RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. 免疫组化、流式细胞术、DNA-seq、RNA-seq、RT-PCR、western blot RUNX2 RUNX2 ensures the expression of pDC-signature genes in leukemic cells, but also confers survival and proliferative properties in BPDCN cells. 30971429 chr7 148804676 148806676 EZH2 Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine 27. human adipose High+Lowthroughput Enhancer of zeste homolog 2 (EZH2) regulates adipocyte lipid metabolism independent of adipogenic differentiation: Role of apolipoprotein E 否 prostate and breast cancer E_02_0267 qPCR、Western blot Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine 27. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine 27. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine 27. qPCR、Western blot EZH2 Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine 27. 30957628 chr12 131892244 131894244 ULK1 Intriguingly, RAB2 appears to modulate ULK1 kinase activity to propagate signals for autophagosome formation. human High+Lowthroughput RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells 否 E_02_0268 Immunofluorescence staining, gel electrophoresis Intriguingly, RAB2 appears to modulate ULK1 kinase activity to propagate signals for autophagosome formation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Intriguingly, RAB2 appears to modulate ULK1 kinase activity to propagate signals for autophagosome formation. Immunohistochemical staining Intriguingly, RAB2 appears to modulate ULK1 kinase activity to propagate signals for autophagosome formation. 免疫荧光染色、凝胶电泳 ULK1 Intriguingly, RAB2 appears to modulate ULK1 kinase activity to propagate signals for autophagosome formation. 30952632 chr3 181709362 181711362 SOX2 The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,2) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generation AR antagonist enzalutamide (Enz), or the androgen-biosynthesis inhibitor abiraterone acetate (3–7). Further, elevated expression of the glucocorticoid receptor can bypass dependence on the AR by promiscuously activating AR target genes (8) or through lineage plasticity driven by SOX2 human High+Lowthroughput Activation of MAPK Signaling by CXCR7 Leads to Enzalutamide Resistance in Prostate Cancer 否 Prostate Cancer E_02_0269 Immunofluorescence staining, immunohistochemistry The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,2) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generation AR antagonist enzalutamide (Enz), or the androgen-biosynthesis inhibitor abiraterone acetate (3–7). Further, elevated expression of the glucocorticoid receptor can bypass dependence on the AR by promiscuously activating AR target genes (8) or through lineage plasticity driven by SOX2 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,2) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generation AR antagonist enzalutamide (Enz), or the androgen-biosynthesis inhibitor abiraterone acetate (3–7). Further, elevated expression of the glucocorticoid receptor can bypass dependence on the AR by promiscuously activating AR target genes (8) or through lineage plasticity driven by SOX2 Immunohistochemical staining The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,2) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generation AR antagonist enzalutamide (Enz), or the androgen-biosynthesis inhibitor abiraterone acetate (3–7). Further, elevated expression of the glucocorticoid receptor can bypass dependence on the AR by promiscuously activating AR target genes (8) or through lineage plasticity driven by SOX2 免疫荧光染色、免疫组化 SOX2,SOX3,SOX4 The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,2) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generation AR antagonist enzalutamide (Enz), or the androgen-biosynthesis inhibitor abiraterone acetate (3–7). Further, elevated expression of the glucocorticoid receptor can bypass dependence on the AR by promiscuously activating AR target genes (8) or through lineage plasticity driven by SOX2;The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,3) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generat;The androgen receptor (AR) is a major driver of the growth of prostate cancer (PCa) (1,4) and aberrant AR signaling remains to play major roles in final-stage castration-resistant prostate cancer (CRPC) that have developed resistance to the second-generat& 30947238 chr7 22723017 22725017 IL6 The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation. human High+Lowthroughput GTS-21 has cell-specific anti-inflammatory effects independent of α7 nicotinic acetylcholine receptors 否 inflammatory E_02_0270 Western blot、 The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation. Immunohistochemical staining The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation. Western blot、 IL6 The α7 nAChR partial agonist GTS-21 reduces secretion of pro-inflammatory cytokines including interleukin-6 (IL6) and tumor-necrosis factor (TNF) in models of endotoxemia and sepsis, and its anti-inflammatory effects are widely ascribed to α7 nAChR activation. 30891136 chr21 38377346 38379346 ERG The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program. human Cancer High+Lowthroughput (18)F-Labeled PET Probe Targeting Enhancer of Zeste Homologue 2 (EZH2) for Cancer Imaging 否 E_02_0271 gel electrophoresis The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program. Immunohistochemical staining The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program. 凝胶电泳 ERG,EZH2 The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program.;(18)F-Labeled PET Probe Targeting Enhancer of Zeste Homologue 2 (EZH2) for Cancer Imaging 33411777 chr7 50301051 50303051 IKZF1 Enhancer polymorphisms at the IKZF1 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds. human lymphoid High+Lowthroughput Enhancer polymorphisms at the IKZF2 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds 是 lymphoblastic leukemia hematopoietic stem cell E_02_0272 PCR, gel electrophoresis, SNP sequencing technology, statistical analysis Enhancer polymorphisms at the IKZF1 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer polymorphisms at the IKZF1 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds. Immunohistochemical staining Enhancer polymorphisms at the IKZF1 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds. PCR、凝胶电泳、SNP测序技术、统计分析 IKZF1 Enhancer polymorphisms at the IKZF1 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds. 31076403 chr11 102107558 102109558 YAP1 The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors. human Immunohistochem High+Lowthroughput Targeting monocyte-intrinsic enhancer reprogramming improves immunotherapy efficacy in hepatocellular carcinoma. 否 hepatocellular carcinoma Myeloid-derived suppressor cell E_02_0273 Flow cytometry, immunofluorescence staining The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors. Immunohistochemical staining The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors. 流式细胞术、免疫荧光染色 YAP1 The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors. 29939784 chr2 216669369 216671369 IGFBP5 We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity. human Adrenal medulla High+Lowthroughput Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ-related signaling pathway 否 Dopaminergic neuron apoptosis chromaffin cell E_02_0274 Luciferase Reporter assay,Western blot,Annexin V apoptosis staining,shRNA and stereotaxic injection,siRNA and transient transfection,TUNEL staining,Electron microscopy,Immunofluorescence labeling, We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity. Immunohistochemical staining We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity. Luciferase Reporter assay,Western blot,Annexin V apoptosis staining,shRNA and stereotaxic injection,siRNA and transient transfection,TUNEL staining,Electron microscopy,Immunofluorescence labeling, IGFBP5,Trib3 We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity.;We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity. 29939173 chr14 6031195 6033195 Top2b In this study, we report a method for the induction of CRISPR-mediated somatic mutations in the cerebellum. Specifically, we utilized conditional knock-in mice, in which Cas9 and GFP are chronically activated by the CAG (CMV enhancer/chicken ß-actin) promoter after Cre-mediated recombination of the genome. The self-designed single-guide RNAs (sgRNAs) and the Cre recombinase sequence, both encoded in a single plasmid construct, were delivered into cerebellar stem/progenitor cells at an embryonic stage using in utero electroporation. Consequently, transfected cells and their daughter cells were labeled with green fluorescent protein (GFP), thus facilitating further phenotypic analyses. Hence, this method is not only showing electroporation-based gene delivery into embryonic cerebellar cells but also proposing a novel quantitative approach to assess CRISPR-mediated loss-of-function phenotypes. mouse Kidney High+Lowthroughput CRISPR-mediated Loss of Function Analysis in Cerebellar Granule Cells Using In Utero Electroporation-based Gene Transfer 否 Brain malformations epithelial cell E_02_0275 Immunostaining,CRISPR/Cas9,transfection,PCR, In this study, we report a method for the induction of CRISPR-mediated somatic mutations in the cerebellum. Specifically, we utilized conditional knock-in mice, in which Cas9 and GFP are chronically activated by the CAG (CMV enhancer/chicken ß-actin) promoter after Cre-mediated recombination of the genome. The self-designed single-guide RNAs (sgRNAs) and the Cre recombinase sequence, both encoded in a single plasmid construct, were delivered into cerebellar stem/progenitor cells at an embryonic stage using in utero electroporation. Consequently, transfected cells and their daughter cells were labeled with green fluorescent protein (GFP), thus facilitating further phenotypic analyses. Hence, this method is not only showing electroporation-based gene delivery into embryonic cerebellar cells but also proposing a novel quantitative approach to assess CRISPR-mediated loss-of-function phenotypes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, we report a method for the induction of CRISPR-mediated somatic mutations in the cerebellum. Specifically, we utilized conditional knock-in mice, in which Cas9 and GFP are chronically activated by the CAG (CMV enhancer/chicken ß-actin) promoter after Cre-mediated recombination of the genome. The self-designed single-guide RNAs (sgRNAs) and the Cre recombinase sequence, both encoded in a single plasmid construct, were delivered into cerebellar stem/progenitor cells at an embryonic stage using in utero electroporation. Consequently, transfected cells and their daughter cells were labeled with green fluorescent protein (GFP), thus facilitating further phenotypic analyses. Hence, this method is not only showing electroporation-based gene delivery into embryonic cerebellar cells but also proposing a novel quantitative approach to assess CRISPR-mediated loss-of-function phenotypes. Immunohistochemical staining In this study, we report a method for the induction of CRISPR-mediated somatic mutations in the cerebellum. Specifically, we utilized conditional knock-in mice, in which Cas9 and GFP are chronically activated by the CAG (CMV enhancer/chicken ß-actin) promoter after Cre-mediated recombination of the genome. The self-designed single-guide RNAs (sgRNAs) and the Cre recombinase sequence, both encoded in a single plasmid construct, were delivered into cerebellar stem/progenitor cells at an embryonic stage using in utero electroporation. Consequently, transfected cells and their daughter cells were labeled with green fluorescent protein (GFP), thus facilitating further phenotypic analyses. Hence, this method is not only showing electroporation-based gene delivery into embryonic cerebellar cells but also proposing a novel quantitative approach to assess CRISPR-mediated loss-of-function phenotypes. Immunostaining,CRISPR/Cas9,transfection,PCR, Top2b In this study, we report a method for the induction of CRISPR-mediated somatic mutations in the cerebellum. Specifically, we utilized conditional knock-in mice, in which Cas9 and GFP are chronically activated by the CAG (CMV enhancer/chicken ß-actin) promoter after Cre-mediated recombination of the genome. The self-designed single-guide RNAs (sgRNAs) and the Cre recombinase sequence, both encoded in a single plasmid construct, were delivered into cerebellar stem/progenitor cells at an embryonic stage using in utero electroporation. Consequently, transfected cells and their daughter cells were labeled with green fluorescent protein (GFP), thus facilitating further phenotypic analyses. Hence, this method is not only showing electroporation-based gene delivery into embryonic cerebellar cells but also proposing a novel quantitative approach to assess CRISPR-mediated loss-of-function phenotypes. 29938678 chr7 45107986 45109986 Bax Inhibition of PI3K/Akt signaling pathway abolished protective effect of curcumin in MSG-induced toxicity in rat thymocytes. Obtained findings suggest that curcumin may attenuate the MSG-induced apoptosis through PI3K/Akt signaling pathway which could be useful in preventing the potential deficiencies in T cell-mediated immunity. mouse Thymus High+Lowthroughput The effect of curcumin and PI3K/Akt inhibitor on monosodium glutamate-induced rat thymocytes toxicity 否 Other thymocyte E_02_0276 FCM,Caspase-3 activity assay,MMP, Inhibition of PI3K/Akt signaling pathway abolished protective effect of curcumin in MSG-induced toxicity in rat thymocytes. Obtained findings suggest that curcumin may attenuate the MSG-induced apoptosis through PI3K/Akt signaling pathway which could be useful in preventing the potential deficiencies in T cell-mediated immunity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inhibition of PI3K/Akt signaling pathway abolished protective effect of curcumin in MSG-induced toxicity in rat thymocytes. Obtained findings suggest that curcumin may attenuate the MSG-induced apoptosis through PI3K/Akt signaling pathway which could be useful in preventing the potential deficiencies in T cell-mediated immunity. Immunohistochemical staining Inhibition of PI3K/Akt signaling pathway abolished protective effect of curcumin in MSG-induced toxicity in rat thymocytes. Obtained findings suggest that curcumin may attenuate the MSG-induced apoptosis through PI3K/Akt signaling pathway which could be useful in preventing the potential deficiencies in T cell-mediated immunity. FCM,Caspase-3 activity assay,MMP, Bax Inhibition of PI3K/Akt signaling pathway abolished protective effect of curcumin in MSG-induced toxicity in rat thymocytes. Obtained findings suggest that curcumin may attenuate the MSG-induced apoptosis through PI3K/Akt signaling pathway which could be useful in preventing the potential deficiencies in T cell-mediated immunity. 29930094 chr12 86405578 86407578 Esrrb Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo. mouse Nervous High+Lowthroughput Mediator and RNA polymerase II clusters associate in transcription-dependent condensates 否 Other embryonic stem cell E_02_0277 Western blot,ChIP-seq,FISH, Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo. Immunohistochemical staining Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo. Western blot,ChIP-seq,FISH, Esrrb,BRD4 Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo.;Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo. 29930005 chr1 162042029 162044029 Dnm3os Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. mouse lymphoid High+Lowthroughput Diabetes Mellitus-Induced Long Noncoding RNA Dnm3os Regulates Macrophage Functions and Inflammation via Nuclear Mechanisms 否 Diabetes mellitus, atherosclerosis macrophage E_02_0278 RNA Isolation,Western Blot,ELISA,ChIP,FISH,RNA-Seq,qRT-PCR, Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. Immunohistochemical staining Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. RNA Isolation,Western Blot,ELISA,ChIP,FISH,RNA-Seq,qRT-PCR, Dnm3os,Ppia,HPRT1,Rplp0 Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. ;Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. ;Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. ;Hese results demonstrate novel mechanisms involving upregulation of long noncoding RNA Dnm3os, disruption of its interaction with nucleolin, and epigenetic modifications at target genes that promote macrophage inflammatory phenotype in diabetes mellitus. The data could lead to long noncoding RNA-based therapies for inflammatory diabetes mellitus complications. 29910149 chr12 86404702 86406702 Esrrb These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information. mouse Nervous High+Lowthroughput Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency 否 Other embryonic stem cell E_02_0279 RT-PCR,Immunofluorescence,Western Blot,Flow Cytometry,Bisulfite Sequencing,ChIP,NOMe-seq,GlucMS-PCR,Luciferase Reporter Assays,Microarray,ChIP-seq,RNA-seq, These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information. Immunohistochemical staining These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information. RT-PCR,Immunofluorescence,Western Blot,Flow Cytometry,Bisulfite Sequencing,ChIP,NOMe-seq,GlucMS-PCR,Luciferase Reporter Assays,Microarray,ChIP-seq,RNA-seq, Esrrb,Sox2,Nanog,Klf4,Klf2,Tbx3 These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.;These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.;These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.;These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.;These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.;These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information. 29908180 chr11 98246620 98248620 Stard3 Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation. mouse adipose High+Lowthroughput Knocking down Stard3 decreases adipogenesis with decreased mitochondrial ROS in 3T3-L1 cells 否 cholesterol 3T3-L1 E_02_0280 Oil red-O staining,Small interfering RNA,Quantitative real-time PCR,Protein isolation,western blot,transfection Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation. Immunohistochemical staining Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation. Oil red-O staining,Small interfering RNA,Quantitative real-time PCR,Protein isolation,western blot,transfection Stard3 Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation. 29907651 chr12 6567592 6569592 CHD4 The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation. human Nervous High+Lowthroughput lncRNA PAPAS tethered to the rDNA enhancer recruits hypophosphorylated CHD4/NuRD to repress rRNA synthesis at elevated temperatures 否 Other NIH3T3 E_02_0281 PCR,siRNA,transfection,competition experiments,In vivo RNA–protein interaction assays,In vitro protein–RNA interaction assays,RNase footprinting,EMSA,Western Blot,Northwestern blot showing binding,Immunoblot,Chromatin immunoprecipitation (ChIP),CLIP,RT–PCR,RNA immunoprecipitation (fRIP) assays, The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation. Immunohistochemical staining The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation. PCR,siRNA,transfection,competition experiments,In vivo RNA–protein interaction assays,In vitro protein–RNA interaction assays,RNase footprinting,EMSA,Western Blot,Northwestern blot showing binding,Immunoblot,Chromatin immunoprecipitation (ChIP),CLIP,RT–PCR,RNA immunoprecipitation (fRIP) assays, CHD4 The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation. 29903884 chr11 112217210 112217767 Sox9 In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9 Although others are redundant, enhancer 13 (Enh13), a 557-base pair element located 565 kilobases 5' from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans. mouse connective Low+High throughput Sex reversal following deletion of a single distal enhancer of Sox9 否 -- Sertoli cell E_02_0282 DNaseI-seq,ChIP-seq In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2 Mb gene desert upstream of Sox9.Although others are redundant, Enh13, a 557 bp element located 565 kb 5’, is essential to initiate mouse testis development. Enhancer CRISPR/Cas9 ChIP-seq,RT-PCR 2010306G03Rik,AV220920,mKIAA4243 Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans. CRISPR/Cas9,RT-qPCR This again supports the conclusion that Enh13 plays a more substantial role than TES during early gonadal development. Tdf,Tdy ChIP-qPCR -- -- Sox9,Sox9,Sox9,Sox9 Sry,Sry,Sry,Sry There was a 30 to 50% decrease in Sox9 mRNA levels in E11.5 XX Enh13-/- gonads compared to the wild type, as reflected by reduced immunofluorescence for SOX9 protein (fig. S11). These data indicate that Enh13 also plays a role in the very early expression of Sox9 in the XX gonad.;There was a 30 to 50% decrease in Sox9 mRNA levels in E11.5 XX Enh13-/- gonads compared to the wild type, as reflected by reduced immunofluorescence for SOX9 protein (fig. S11). These data indicate that Enh13 also plays a role in the very early expression of Sox9 in the XX gonad.;There was a 30 to 50% decrease in Sox9 mRNA levels in E11.5 XX Enh13-/- gonads compared to the wild type, as reflected by reduced immunofluorescence for SOX9 protein (fig. S11). These data indicate that Enh13 also plays a role in the very early expression of Sox9 in the XX gonad.;There was a 30 to 50% decrease in Sox9 mRNA levels in E11.5 XX Enh13-/- gonads compared to the wild type, as reflected by reduced immunofluorescence for SOX9 protein (fig. S11). These data indicate that Enh13 also plays a role in the very early expression of Sox9 in the XX gonad. We performed ChIP-qPCR on E11.5 gonads dissected from Sry-Myc transgenic embryos by using a specific antibody against the MYC tag.SRY-MYC–positive gonads had an 11-fold enrichment versus SRY-MYC–negative gonads with primers spanning the SOX9 consensus site and a sixfold enrichment with primers spanning the SRY site, whereas primers against the strongest SRY binding site in TESCO showed fivefold enrichment.This reveals the strong binding of SRY to Enh13 at E11.5, with a preference for the SOX9 consensus site, possibly due to the adjacent SF1 binding site.;We performed ChIP-qPCR on E11.5 gonads dissected from Sry-Myc transgenic embryos by using a specific antibody against the MYC tag.SRY-MYC–positive gonads had an 11-fold enrichment versus SRY-MYC–negative gonads with primers spanning the SOX9 consensus site and a sixfold enrichment with primers spanning the SRY site, whereas primers against the strongest SRY binding site in TESCO showed fivefold enrichment.This reveals the strong binding of SRY to Enh13 at E11.5, with a preference for the SOX9 consensus site, possibly due to the adjacent SF1 binding site.;We performed ChIP-qPCR on E11.5 gonads dissected from Sry-Myc transgenic embryos by using a specific antibody against the MYC tag.SRY-MYC–positive gonads had an 11-fold enrichment versus SRY-MYC–negative gonads with primers spanning the SOX9 consensus site and a sixfold enrichment with primers spanning the SRY site, whereas primers against the strongest SRY binding site in TESCO showed fivefold enrichment.This reveals the strong binding of SRY to Enh13 at E11.5, with a preference for the SOX9 consensus site, possibly due to the adjacent SF1 binding site.;We performed ChIP-qPCR on E11.5 gonads dissected from Sry-Myc transgenic embryos by using a specific antibody against the MYC tag.SRY-MYC–positive gonads had an 11-fold enrichment versus SRY-MYC–negative gonads with primers spanning the SOX9 consensus site and a sixfold enrichment with primers spanning the SRY site, whereas primers against the strongest SRY binding site in TESCO showed fivefold enrichment.This reveals the strong binding of SRY to Enh13 at E11.5, with a preference for the SOX9 consensus site, possibly due to the adjacent SF1 binding site. 29903739 chr15 96725740 96737960 Tbx20 Myocardial TBX20 directly regulates a subset of genes required for fetal cardiomyocyte proliferation, including those required for the G1-S transition. TBX20 also directly downregulates progenitor-specific genes and, in addition to regulating genes that specify chamber versus nonchamber myocardium, directly activates genes required for establishment or maintenance of atrial and ventricular identity. TBX20 plays a previously unappreciated key role in atrial development through direct regulation of an evolutionarily conserved COUPT-FII enhancer. mouse Nervous Low+High throughput Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development 否 Congenital Heart Disease cardiac muscle cell (sensu Arthopoda) E_02_0283 ChIP-seq,Hi-C we made use of our TBX20 ChIP-Seq analysis in E11.5 hearts and attributed TBX20 bound sites to the nearest expressed gene in E11.5 control or Tbx20 cKO cardiomyocytes. Next, we overlaid our RNA-Seq data with that of our TBX20 ChIP-Seq analysis in E11.5 hearts and identified 548 genes that were differentially expressed in Tbx20 cKO cardiomyocytes and were marked by one or more TBX20 binding events in the vicinity of the gene. Enhancer -- Hi-C ARP-1,ARP1,CHTD4,COUPTF2,COUPTFB,COUPTFII,NF-E3,SVP40,TFCOUP2 This Enhancer interacted with the NR2F2 promoter in human cardiomyocytes and conferred atrial specific gene expression in a transgenic mouse in a TBX20 dependent manner. Hi-C Taken together, these results linked TBX20 binding to an evolutionary conserved Enhancer that regulates COUP-TFII expression in developing atrial cardiomyocytes, uncovering a mechanism by which COUP-TFII expression is TBX20 dependent. ASD4 X-Gal Staining Assay -- -- NR2F2,NR2F2,NR2F2 TBX20,TBX20,TBX20 We next established that this Enhancer was functionally connected with COUP-TFII. We performed a promoter-based Capture Hi-C in iPSC-derived human cardiomyocytes to identify long-range physical interactions between genes and Enhancers. We observed that this Enhancer directly loops and contacts the COUP-TFII promoter,140-Kb away,confirming that this is a COUP-TFII Enhancer.;We next established that this Enhancer was functionally connected with COUP-TFII. We performed a promoter-based Capture Hi-C in iPSC-derived human cardiomyocytes to identify long-range physical interactions between genes and Enhancers. We observed that this Enhancer directly loops and contacts the COUP-TFII promoter,140-Kb away,confirming that this is a COUP-TFII Enhancer.;We next established that this Enhancer was functionally connected with COUP-TFII. We performed a promoter-based Capture Hi-C in iPSC-derived human cardiomyocytes to identify long-range physical interactions between genes and Enhancers. We observed that this Enhancer directly loops and contacts the COUP-TFII promoter,140-Kb away,confirming that this is a COUP-TFII Enhancer. Section analysis of COUP-TFII enh1::lacZ transgenic embryo demonstrates X-gal staining in developing atrial myocardium (arrows) and caval vein (arrowheads). ;Section analysis of COUP-TFII enh1::lacZ transgenic embryo demonstrates X-gal staining in developing atrial myocardium (arrows) and caval vein (arrowheads). ;Section analysis of COUP-TFII enh1::lacZ transgenic embryo demonstrates X-gal staining in developing atrial myocardium (arrows) and caval vein (arrowheads). 29902458 chr16 29880836 29882836 Hes1 In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis. mouse Nervous High+Lowthroughput MicroRNA-374b promotes the proliferation and differentiation of neural stem cells through targeting Hes1 否 Other neuronal stem cell E_02_0284 RT-qPCR,Immunocytochemistry,Western blot,Cell transfection,Dual-luciferase reporter assay,Cell proliferation assay, In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis. Immunohistochemical staining In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis. RT-qPCR,Immunocytochemistry,Western blot,Cell transfection,Dual-luciferase reporter assay,Cell proliferation assay, Hes1 In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis. 29897487 chr4 55524704 55526704 Klf4 Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%). mouse Epithelial High+Lowthroughput Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis 否 Colorectal inflammation goblet cell E_02_0285 qRT-PCR,Immunohistochemical analysis,Immunoblotting analysis Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%). Immunohistochemical staining Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%). qRT-PCR,Immunohistochemical analysis,Immunoblotting analysis Klf4,Hes1,Muc2,STAT3 Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%).;Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%).;Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%).;Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%). 29893919 chr8 38139821 38141821 STAR Herein, we provide investigators with rationale for each step in the MMARGE pipeline and key differences for analysis of datasets with different experimental designs. We demonstrate the utility of MMARGE using mouse peritoneal macrophages, liver cells, and human lymphoblastoid cells. MMARGE provides a powerful tool to identify combinations of cell type-specific transcription factors while simultaneously interpreting functional effects of non-coding genetic variation. human lymphoid High+Lowthroughput MMARGE: Motif Mutation Analysis for Regulatory Genomic Elements 否 Other peritoneal macrophages E_02_0286 ATAC-seq,DNase I,CHIP-seq,GWAS, Herein, we provide investigators with rationale for each step in the MMARGE pipeline and key differences for analysis of datasets with different experimental designs. We demonstrate the utility of MMARGE using mouse peritoneal macrophages, liver cells, and human lymphoblastoid cells. MMARGE provides a powerful tool to identify combinations of cell type-specific transcription factors while simultaneously interpreting functional effects of non-coding genetic variation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Herein, we provide investigators with rationale for each step in the MMARGE pipeline and key differences for analysis of datasets with different experimental designs. We demonstrate the utility of MMARGE using mouse peritoneal macrophages, liver cells, and human lymphoblastoid cells. MMARGE provides a powerful tool to identify combinations of cell type-specific transcription factors while simultaneously interpreting functional effects of non-coding genetic variation. Immunohistochemical staining Herein, we provide investigators with rationale for each step in the MMARGE pipeline and key differences for analysis of datasets with different experimental designs. We demonstrate the utility of MMARGE using mouse peritoneal macrophages, liver cells, and human lymphoblastoid cells. MMARGE provides a powerful tool to identify combinations of cell type-specific transcription factors while simultaneously interpreting functional effects of non-coding genetic variation. ATAC-seq,DNase I,CHIP-seq,GWAS, STAR Herein, we provide investigators with rationale for each step in the MMARGE pipeline and key differences for analysis of datasets with different experimental designs. We demonstrate the utility of MMARGE using mouse peritoneal macrophages, liver cells, and human lymphoblastoid cells. MMARGE provides a powerful tool to identify combinations of cell type-specific transcription factors while simultaneously interpreting functional effects of non-coding genetic variation. 29881822 chr15 59517953 59519953 Trib1 Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. mouse Nervous High+Lowthroughput Neutrophils alleviate fibrosis in the CCl(4)-induced mouse chronic liver injury model 否 Chronic liver injury neutrophils E_02_0287 qPCR,Western Blot,RT-PCR,real-time PCR,flow cytometry Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. Immunohistochemical staining Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. qPCR,Western Blot,RT-PCR,real-time PCR,flow cytometry Trib1,Mmp8,Mmp9,Cxcl1 Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis.;Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis.;Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis.;Consistently, transplantation of Trib1-deficient bone marrow cells into wild-type mice alleviated CCl4-induced fibrosis. Furthermore, expression of chemokine (C-X-C motif) ligand 1 (Cxcl1) by adeno-associated viral vector in the normal liver recruited neutrophils and suppressed CCl4-induced fibrosis; infusion of wild-type neutrophils in CCl4-treated mice also ameliorated fibrosis. Using recombinant adeno-associated virus-mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4-induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. 29874843 chr9 4981763 4983763 JAK2 Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. human hepatic High+Lowthroughput Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis 否 Obesity hepatocyte E_02_0288 RT-PCR,Western Blot,AST,ALT, Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. Immunohistochemical staining Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. RT-PCR,Western Blot,AST,ALT, JAK2,STAT3 Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.;Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. 29867706 chr13 30454393 30456393 HMGB1 We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway. human Nervous High+Lowthroughput Ursolic Acid Ameliorates Inflammation in Cerebral Ischemia and Reperfusion Injury Possibly via High Mobility Group Box 1/Toll-Like Receptor 4/NFκB Pathway 否 Inflammation in cerebral ischemia, reperfusion injury microglial cell E_02_0289 Nissl staining, ELISA,immunofluorescence staining,Western Blot,immunohistochemical staining We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway. Immunohistochemical staining We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway. Nissl staining, ELISA,immunofluorescence staining,Western Blot,immunohistochemical staining HMGB1,TLR4 We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway.;We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the HMGB1/TLR4/NFκB signaling pathway. 29854630 chr10 71059112 71061112 Tfam These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats. mouse Epithelial High+Lowthroughput Capsaicinoids improve consequences of physical activity 否 inflammation endothelial cell E_02_0290 Western blot These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats. Immunohistochemical staining These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats. Western blot Tfam These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats. 29852820 chr11 102833101 102835101 MMP3 miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1β by targeting C/EBPβ in rat NP cells. human lymphoid High+Lowthroughput MicroRNA-155 suppresses the catabolic effect induced by TNF-α and IL-1β by targeting C/EBPβ in rat nucleus pulposus cells 否 Disc degeneration natural killer cell E_02_0291 Dual Luciferase Reporter Assay, real-time PCR,Western Blot,MRI,HE staining,collagen II immunochemistry,transgenic mice,Histology,immunohistochemistry,C/EBPβ knockdown,transfection,PCR miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1β by targeting C/EBPβ in rat NP cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1β by targeting C/EBPβ in rat NP cells. Immunohistochemical staining miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1β by targeting C/EBPβ in rat NP cells. Dual Luciferase Reporter Assay, real-time PCR,Western Blot,MRI,HE staining,collagen II immunochemistry,transgenic mice,Histology,immunohistochemistry,C/EBPβ knockdown,transfection,PCR MMP3,GAPDH miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1β by targeting C/EBPβ in rat NP cells.;miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-α and IL-1β by targeting C/EBPβ in rat NP cells. 29851521 chr6 151654399 151656399 ESR1 This study successfully used TP to develop a DA patch with good anti-inflammatory and analgesic effects, proving that TP promotes the release of DA by reducing the interaction between DA and PSA and increasing the mobility of PSA. human Epithelial High+Lowthroughput Development of a daphnetin transdermal patch using chemical enhancer strategy: insights of the enhancement effect of Transcutol P and the assessment of pharmacodynamics 否 Other stratified squamous epithelium cell E_02_0292 HPLC,DSC,FTIR This study successfully used TP to develop a DA patch with good anti-inflammatory and analgesic effects, proving that TP promotes the release of DA by reducing the interaction between DA and PSA and increasing the mobility of PSA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study successfully used TP to develop a DA patch with good anti-inflammatory and analgesic effects, proving that TP promotes the release of DA by reducing the interaction between DA and PSA and increasing the mobility of PSA. Immunohistochemical staining This study successfully used TP to develop a DA patch with good anti-inflammatory and analgesic effects, proving that TP promotes the release of DA by reducing the interaction between DA and PSA and increasing the mobility of PSA. HPLC,DSC,FTIR ESR1 This study successfully used TP to develop a DA patch with good anti-inflammatory and analgesic effects, proving that TP promotes the release of DA by reducing the interaction between DA and PSA and increasing the mobility of PSA. 29849691 chr10 88950862 88952862 FAS We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo. human adipose High+Lowthroughput Glehnia littoralis Root Extract Inhibits Fat Accumulation in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice by Downregulating Adipogenic Gene Expression 否 Obesity 3T3-L1 E_02_0293 RT-PCR,western blot,oil red O staining,High-Performance Liquid Chromatography (HPLC) We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo. Immunohistochemical staining We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo. RT-PCR,western blot,oil red O staining,High-Performance Liquid Chromatography (HPLC) FAS We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo. 29848344 chr14 73418621 73420621 Rb1 Our study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases. mouse connective High+Lowthroughput Microarray analysis of long non-coding RNA expression profiles in monocytic myeloid-derived suppressor cells in Echinococcus granulosus-infected mice 否 Cystic echinococcosis, a chronic zoonotic disease E_02_0294 Microarray profiling,Quantitative reverse transcription-PCR (qRT-PCR),Cis- and trans-regulation analysis Our study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases. Immunohistochemical staining Our study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases. Microarray profiling,Quantitative reverse transcription-PCR (qRT-PCR),Cis- and trans-regulation analysis Rb1 Our study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases. 29847803 chr7 34815681 34817681 Cebpa Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. mouse connective High+Lowthroughput Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors 否 Other E_02_0295 ChIP-seq,ATAC-seq,scRNA-seq,RNA-Seq,ATAC-qPCR Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. Immunohistochemical staining Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. ChIP-seq,ATAC-seq,scRNA-seq,RNA-Seq,ATAC-qPCR Cebpa,CEBPA Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation.;Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. 29846108 chrX 154019316 154021316 MECP2 In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression. human Nervous High+Lowthroughput MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis 否 Other E_02_0296 AVP-enhancer reporter assay,Western blot,RT-qPCR,Immunohistochemistry In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression. Immunohistochemical staining In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression. AVP-enhancer reporter assay,Western blot,RT-qPCR,Immunohistochemistry MECP2,AVP In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression.;In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression. 29844424 chr17 63474572 63476572 ACE In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE. human Nervous High+Lowthroughput Increased H3K27ac level of ACE mediates the intergenerational effect of low peak bone mass induced by prenatal dexamethasone exposure in male offspring rats 否 Low peak bone mass BMSCs E_02_0297 ELISA,Total RNA extraction,RT-qPCR,Alizarin Red S staining,siRNA knockdown,Western blot,Histological,immunohistochemistry analysis,Chromatin immunoprecipitation (ChIP) assay In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE. Immunohistochemical staining In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE. ELISA,Total RNA extraction,RT-qPCR,Alizarin Red S staining,siRNA knockdown,Western blot,Histological,immunohistochemistry analysis,Chromatin immunoprecipitation (ChIP) assay ACE In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE. 29807547 chr21 38377160 38379160 ERG "Our results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a ""default"" differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects." human connective High+Lowthroughput Establishment of regulatory elements during erythro-megakaryopoiesis identifies hematopoietic lineage-commitment points 否 Other LSK cell E_02_0298 ATAC-Seq,ChIP-Seq,MBD‑Seq,RNA‑Seq,flow cytometry,indexing-first immunoprecipitation(iChIP) "Our results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a ""default"" differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects." Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq "Our results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a ""default"" differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects." Immunohistochemical staining "Our results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a ""default"" differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects." ATAC-Seq,ChIP-Seq,MBD‑Seq,RNA‑Seq,flow cytometry,indexing-first immunoprecipitation(iChIP) ERG,ETS1 "Our results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a ""default"" differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects.;Our results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a ""default"" differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects." 29798841 chr1 51786244 51788244 NRDC Nrdc inhibits pancreatitis and suppresses PDA initiation in mice. human Nervous High+Lowthroughput Nardilysin inhibits pancreatitis and suppresses pancreatic ductal adenocarcinoma initiation in mice 否 Pancreatitis, murine pancreatic ductal adenocarcinoma (PDA), pancreatic intraepithelial lesion (PanIN) ES E_02_0299 Southern blot,PCR,qRT-PCR,immunohistochemistry,immunofluorescence staining,immunostaining,microarray analysis Nrdc inhibits pancreatitis and suppresses PDA initiation in mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nrdc inhibits pancreatitis and suppresses PDA initiation in mice. Immunohistochemical staining Nrdc inhibits pancreatitis and suppresses PDA initiation in mice. Southern blot,PCR,qRT-PCR,immunohistochemistry,immunofluorescence staining,immunostaining,microarray analysis NRDC,KRAS Nrdc inhibits pancreatitis and suppresses PDA initiation in mice.;Nrdc inhibits pancreatitis and suppresses PDA initiation in mice. 29779944 chr3 133743368 133745368 TF Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. human High+Lowthroughput Analysis of Genetically Diverse Macrophages Reveals Local and Domain-wide Mechanisms that Control Transcription Factor Binding and Function 否 Other L929 E_02_0300 RNA-seq,ChIP-seq,5' GRO-seq,GRO-seq,ATAC-seq,PLAC-seq,Bisulfite Sequencing,Hi-C,WGCNA analysis Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. Immunohistochemical staining Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. RNA-seq,ChIP-seq,5' GRO-seq,GRO-seq,ATAC-seq,PLAC-seq,Bisulfite Sequencing,Hi-C,WGCNA analysis TF,Igf1,GABPA,DBP Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages.;Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages.;Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages.;Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. 29777232 chr12 4002608 4004608 Pomc With maternal HF diet, offspring at weaning had rapid early weight gain, increased adiposity, and hyperleptinemia. The programmed adult offspring, subsequently fed LF diet, retained the increased body weight. Maternal HF diet combined with offspring HF diet caused more pronounced hyperphagia, fat mass, and insulin resistance. The ARC Pomc gene from programmed offspring at weaning showed hypermethylation in the enhancer (nPE1 and nPE2) regions and in the promoter sequence mediating leptin effects. Interestingly, hypermethylation at the Pomc promoter but not at the enhancer region persisted long term into adulthood in the programmed offspring. However, there were no additive effects on methylation levels in the regulatory regions of Pomc in programmed offspring fed a HF diet. mouse / High+Lowthroughput Maternal overnutrition programs epigenetic changes in the regulatory regions of hypothalamic Pomc in the offspring of rats 否 Obesity, diabetes E_02_0301 Quantitative reverse-transcription PCR,DNA methylation analysis,Enzyme-linked immunosorbent assay With maternal HF diet, offspring at weaning had rapid early weight gain, increased adiposity, and hyperleptinemia. The programmed adult offspring, subsequently fed LF diet, retained the increased body weight. Maternal HF diet combined with offspring HF diet caused more pronounced hyperphagia, fat mass, and insulin resistance. The ARC Pomc gene from programmed offspring at weaning showed hypermethylation in the enhancer (nPE1 and nPE2) regions and in the promoter sequence mediating leptin effects. Interestingly, hypermethylation at the Pomc promoter but not at the enhancer region persisted long term into adulthood in the programmed offspring. However, there were no additive effects on methylation levels in the regulatory regions of Pomc in programmed offspring fed a HF diet. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq With maternal HF diet, offspring at weaning had rapid early weight gain, increased adiposity, and hyperleptinemia. The programmed adult offspring, subsequently fed LF diet, retained the increased body weight. Maternal HF diet combined with offspring HF diet caused more pronounced hyperphagia, fat mass, and insulin resistance. The ARC Pomc gene from programmed offspring at weaning showed hypermethylation in the enhancer (nPE1 and nPE2) regions and in the promoter sequence mediating leptin effects. Interestingly, hypermethylation at the Pomc promoter but not at the enhancer region persisted long term into adulthood in the programmed offspring. However, there were no additive effects on methylation levels in the regulatory regions of Pomc in programmed offspring fed a HF diet. Immunohistochemical staining With maternal HF diet, offspring at weaning had rapid early weight gain, increased adiposity, and hyperleptinemia. The programmed adult offspring, subsequently fed LF diet, retained the increased body weight. Maternal HF diet combined with offspring HF diet caused more pronounced hyperphagia, fat mass, and insulin resistance. The ARC Pomc gene from programmed offspring at weaning showed hypermethylation in the enhancer (nPE1 and nPE2) regions and in the promoter sequence mediating leptin effects. Interestingly, hypermethylation at the Pomc promoter but not at the enhancer region persisted long term into adulthood in the programmed offspring. However, there were no additive effects on methylation levels in the regulatory regions of Pomc in programmed offspring fed a HF diet. Quantitative reverse-transcription PCR,DNA methylation analysis,Enzyme-linked immunosorbent assay Pomc With maternal HF diet, offspring at weaning had rapid early weight gain, increased adiposity, and hyperleptinemia. The programmed adult offspring, subsequently fed LF diet, retained the increased body weight. Maternal HF diet combined with offspring HF diet caused more pronounced hyperphagia, fat mass, and insulin resistance. The ARC Pomc gene from programmed offspring at weaning showed hypermethylation in the enhancer (nPE1 and nPE2) regions and in the promoter sequence mediating leptin effects. Interestingly, hypermethylation at the Pomc promoter but not at the enhancer region persisted long term into adulthood in the programmed offspring. However, there were no additive effects on methylation levels in the regulatory regions of Pomc in programmed offspring fed a HF diet. 29775417 chr7 148804568 148806568 EZH2 These data indicate that EZH2 activation contributes to renal EMT and fibrosis through activation of multiple signaling pathways and suggest that EZH2 has potential as a therapeutic target for treatment of renal fibrosis.-Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. human Kidney High+Lowthroughput Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis 否 Renal fibrosis kidney tubule cell E_02_0302 Transfection of siRNA,Immunoblot analysis,Histochemical,immunofluorescent staining,Densitometry analysis These data indicate that EZH2 activation contributes to renal EMT and fibrosis through activation of multiple signaling pathways and suggest that EZH2 has potential as a therapeutic target for treatment of renal fibrosis.-Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These data indicate that EZH2 activation contributes to renal EMT and fibrosis through activation of multiple signaling pathways and suggest that EZH2 has potential as a therapeutic target for treatment of renal fibrosis.-Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. Immunohistochemical staining These data indicate that EZH2 activation contributes to renal EMT and fibrosis through activation of multiple signaling pathways and suggest that EZH2 has potential as a therapeutic target for treatment of renal fibrosis.-Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. Transfection of siRNA,Immunoblot analysis,Histochemical,immunofluorescent staining,Densitometry analysis EZH2 These data indicate that EZH2 activation contributes to renal EMT and fibrosis through activation of multiple signaling pathways and suggest that EZH2 has potential as a therapeutic target for treatment of renal fibrosis.-Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. 29772805 chr19 48952280 48954280 BAX This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway. human Nervous High+Lowthroughput Ethyl Acetate Fraction from Persimmon (Diospyros kaki) Ameliorates Cerebral Neuronal Loss and Cognitive Deficit via the JNK/Akt Pathway in TMT-Induced Mice 否 Cerebral neuronal loss and cognitive deficits HT22 cell E_02_0303 Western Blot,transgenic mice This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway. Immunohistochemical staining This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway. Western Blot,transgenic mice BAX This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway. 29771444 chr6 45325483 45327483 RUNX2 In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of β-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation. human connective High+Lowthroughput Low-level laser irradiation promotes the differentiation of bone marrow stromal cells into osteoblasts through the APN/Wnt/β-catenin pathway 否 Non small cell lung cancer mesenchymal stem cell E_02_0304 Immunofluorescence,Alkaline Phosphatase (AP) Stain,Western Blot,Alizarin Red Stain,Oil Red O Stain,RT-PCR,cell transfection In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of β-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of β-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation. Immunohistochemical staining In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of β-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation. Immunofluorescence,Alkaline Phosphatase (AP) Stain,Western Blot,Alizarin Red Stain,Oil Red O Stain,RT-PCR,cell transfection RUNX2 In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of β-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation. 29766758 chr11 112140806 112142806 IL18 Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion. human Nervous High+Lowthroughput Anti-Inflammatory Peptide Attenuates Edema and Promotes BMP-2-Induced Bone Formation in Spine Fusion 否 inflammation fibroblast E_02_0305 DNA binding activity,RT-PCR,hematoxylin/eosin (H&E) staining, Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion. Immunohistochemical staining Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion. DNA binding activity,RT-PCR,hematoxylin/eosin (H&E) staining, IL18 Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion. 29765866 chr6 31572670 31574670 TNF These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation. human lymphoid High+Lowthroughput Effects of endosulfan isomers on cytokine and nitric oxide production by differentially activated RAW 264.7 cells 否 inflammation RAW 264.7 CELLS E_02_0306 Cytotoxicity assays,Nitrite assays,ELISAs These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation. Immunohistochemical staining These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation. Cytotoxicity assays,Nitrite assays,ELISAs TNF These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation. 29765516 chr21 40003867 40015913 GFI1B Collectively, the selective separation of LSD1 from GFI1B by NCD38 restores the ERG super-enhancer activation and consequently upregulates ERG expression, inducing the transdifferentiation linked to the anti-leukemia effect. human connective Low+High throughput Selective dissociation between LSD1 and GFI1B by a LSD1 inhibitor NCD38 induces the activation of ERG super-enhancer in erythroleukemia cells 否 Leukemia HEL cell E_02_0307 ChIP-qPCR,ChIP-seq Chromatin-immunoprecipitation followed by quantitative PCR (ChIP-qPCR) analysis for GFI1B and RUNX1 was performed at highly conserved noncoding areas including upstream, promotor, 3’ UTR, and SE regions. Super-Enhancer -- ChIP-qPCR erg-3,p55 -- -- -- BDPLT17,ZNF163B,AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1, PEBP2aB, PEBP2alpha,AOF2, BHC110, CPRF, KDM1, LSD1 ChIP-qPCR -- -- ERG,ERG,ERG,ERG GFI1B,RUNX1,KDM1A,GFI1B,RUNX1,KDM1A,GFI1B,RUNX1,KDM1A,GFI1B,RUNX1,KDM1A Furthermore,ChIP-qPCR analysis for H3K27ac revealed that the level of H3K27ac was elevated only at the SE region after the NCD38 treatment.;Furthermore,ChIP-qPCR analysis for H3K27ac revealed that the level of H3K27ac was elevated only at the SE region after the NCD38 treatment.;Furthermore,ChIP-qPCR analysis for H3K27ac revealed that the level of H3K27ac was elevated only at the SE region after the NCD38 treatment.;Furthermore,ChIP-qPCR analysis for H3K27ac revealed that the level of H3K27ac was elevated only at the SE region after the NCD38 treatment. ChIP-qPCR analysis for GFI1B, RUNX1, or control IgG in the conserved non-coding regions at the ERG locus in HEL cells.ChIP-qPCR analysis for GFI1B (C), LSD1 (D), and CoREST (E) at the ERG-SE locus in HEL cells treated with DMSO or NCD38 for 24 hours. All ChIP-qPCR assays were performed independently twice and the means are displayed.;ChIP-qPCR analysis for GFI1B, RUNX1, or control IgG in the conserved non-coding regions at the ERG locus in HEL cells.ChIP-qPCR analysis for GFI1B (C), LSD1 (D), and CoREST (E) at the ERG-SE locus in HEL cells treated with DMSO or NCD38 for 24 hours. All ChIP-qPCR assays were performed independently twice and the means are displayed.;ChIP-qPCR analysis for GFI1B, RUNX1, or control IgG in the conserved non-coding regions at the ERG locus in HEL cells.ChIP-qPCR analysis for GFI1B (C), LSD1 (D), and CoREST (E) at the ERG-SE locus in HEL cells treated with DMSO or NCD38 for 24 hours. All ChIP-qPCR assays were performed independently twice and the means are displayed.;ChIP-qPCR analysis for GFI1B, RUNX1, or control IgG in the conserved non-coding regions at the ERG locus in HEL cells.ChIP-qPCR analysis for GFI1B (C), LSD1 (D), and CoREST (E) at the ERG-SE locus in HEL cells treated with DMSO or NCD38 for 24 hours. All ChIP-qPCR assays were performed independently twice and the means are displayed. 29761871 chr18 63121195 63123195 BCL2 Autophagy was suppressed in the PNALD model, which was demonstrated by less light chain 3 fluorescence (LC3) puncta and lower LC3II expression. Rapamycin effectively induced hepatic autophagy in PN rats. The PN + Rapa group presented improved hepatic function, decreased pathology scores, and less steatosis than the PN group. In addition, rapamycin treatment decreased terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved-caspase 3 expression, indicating a lower level of hepatocyte apoptosis. Compared with the PN group, the PN + Rapa group had lower levels of ROS and reduced expression of ER stress-related protein markers, such as BIP, sXBP1 and CHOP. human Liver High+Lowthroughput Autophagy May Protect Against Parenteral Nutrition-Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress 否 Parenteral nutrition (PN) - associated liver disease (PNALD) LC3 cell E_02_0308 Immunofluorescence staining,Oil red staining,Immunohistochemistry,TUNEL staining,Western blot Autophagy was suppressed in the PNALD model, which was demonstrated by less light chain 3 fluorescence (LC3) puncta and lower LC3II expression. Rapamycin effectively induced hepatic autophagy in PN rats. The PN + Rapa group presented improved hepatic function, decreased pathology scores, and less steatosis than the PN group. In addition, rapamycin treatment decreased terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved-caspase 3 expression, indicating a lower level of hepatocyte apoptosis. Compared with the PN group, the PN + Rapa group had lower levels of ROS and reduced expression of ER stress-related protein markers, such as BIP, sXBP1 and CHOP. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Autophagy was suppressed in the PNALD model, which was demonstrated by less light chain 3 fluorescence (LC3) puncta and lower LC3II expression. Rapamycin effectively induced hepatic autophagy in PN rats. The PN + Rapa group presented improved hepatic function, decreased pathology scores, and less steatosis than the PN group. In addition, rapamycin treatment decreased terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved-caspase 3 expression, indicating a lower level of hepatocyte apoptosis. Compared with the PN group, the PN + Rapa group had lower levels of ROS and reduced expression of ER stress-related protein markers, such as BIP, sXBP1 and CHOP. Immunohistochemical staining Autophagy was suppressed in the PNALD model, which was demonstrated by less light chain 3 fluorescence (LC3) puncta and lower LC3II expression. Rapamycin effectively induced hepatic autophagy in PN rats. The PN + Rapa group presented improved hepatic function, decreased pathology scores, and less steatosis than the PN group. In addition, rapamycin treatment decreased terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved-caspase 3 expression, indicating a lower level of hepatocyte apoptosis. Compared with the PN group, the PN + Rapa group had lower levels of ROS and reduced expression of ER stress-related protein markers, such as BIP, sXBP1 and CHOP. Immunofluorescence staining,Oil red staining,Immunohistochemistry,TUNEL staining,Western blot BCL2 Autophagy was suppressed in the PNALD model, which was demonstrated by less light chain 3 fluorescence (LC3) puncta and lower LC3II expression. Rapamycin effectively induced hepatic autophagy in PN rats. The PN + Rapa group presented improved hepatic function, decreased pathology scores, and less steatosis than the PN group. In addition, rapamycin treatment decreased terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved-caspase 3 expression, indicating a lower level of hepatocyte apoptosis. Compared with the PN group, the PN + Rapa group had lower levels of ROS and reduced expression of ER stress-related protein markers, such as BIP, sXBP1 and CHOP. 29760677 chr22 39516870 39518870 ATF4 Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved. human adipose High+Lowthroughput One-Week Exposure to a Free-Choice High-Fat High-Sugar Diet Does Not Interfere With the Lipopolysaccharide-Induced Acute Phase Response in the Hypothalamus of Male Rats 否 Obesity, low-grade hypothalamic inflammation fat cell E_02_0309 Western blot,RT-PCR, Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved. Immunohistochemical staining Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved. Western blot,RT-PCR, ATF4,Nfkbia,TLR4,Socs3,NFKBIA Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.;Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.;Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.;Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.;Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved. 29757144 chr16 67559951 67561951 CTCF These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. human Liver High+Lowthroughput Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver 否 Other CH12 cell E_02_0310 ChIP,qPCR,PCR,4C-seq,Motif analysis,ChIP-seq,Sonication,CAC sites and score,Intra-TAD loop prediction method,RNA-seq,Hi-C,Alternative loop anchor analysis,ChIA-PET, These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. Immunohistochemical staining These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. ChIP,qPCR,PCR,4C-seq,Motif analysis,ChIP-seq,Sonication,CAC sites and score,Intra-TAD loop prediction method,RNA-seq,Hi-C,Alternative loop anchor analysis,ChIA-PET, CTCF,TF These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity.;These findings elucidate the role of intra-TAD cohesin-and-CTCF binding in nuclear organization associated with widespread insulation of distal enhancer activity. 29753018 chr7 30330197 30332197 Etv2 In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein. mouse Nervous High+Lowthroughput ETS transcription factor Etsrp / Etv2 is required for lymphangiogenesis and directly regulates vegfr3 / flt4 expression 否 Other murine embryonic stem (ES) cell E_02_0311 Etv2 knockdown,In situ hybridization(ISH),Luciferase experiments,Chromatin immunoprecipitation and sequencing (ChIP-Seq),immunohistochemistry,Dual‐Luciferase Reporter Assay,PCR, In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein. Immunohistochemical staining In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein. Etv2 knockdown,In situ hybridization(ISH),Luciferase experiments,Chromatin immunoprecipitation and sequencing (ChIP-Seq),immunohistochemistry,Dual‐Luciferase Reporter Assay,PCR, Etv2 In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein. 29752714 chr6 64703439 64705439 Atoh1 In the present study, to address this issue, we examined in detail the behavior of post-crossing dI1 axons in mice, using the Atoh1 enhancer-based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs).Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output. mouse Nervous High+Lowthroughput Post-crossing segment of dI1 commissural axons forms collateral branches to motor neurons in the developing spinal cord 否 Other E_02_0312 Hb9 and ChAT immunohistochemistry,Whole-mount immunohistochemistry,Immunostaining, In the present study, to address this issue, we examined in detail the behavior of post-crossing dI1 axons in mice, using the Atoh1 enhancer-based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs).Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, to address this issue, we examined in detail the behavior of post-crossing dI1 axons in mice, using the Atoh1 enhancer-based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs).Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output. Immunohistochemical staining In the present study, to address this issue, we examined in detail the behavior of post-crossing dI1 axons in mice, using the Atoh1 enhancer-based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs).Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output. Hb9 and ChAT immunohistochemistry,Whole-mount immunohistochemistry,Immunostaining, Atoh1 In the present study, to address this issue, we examined in detail the behavior of post-crossing dI1 axons in mice, using the Atoh1 enhancer-based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs).Our findings thus reveal a previously unrecognized projection of dI1 commissural axons that may contribute directly to generating proper motor output. 29752567 chr7 148804760 148806760 EZH2 EZH2 is upregulated, whereas inhibiting EZH2 exerted rescuing effect in anesthetics (bupivacaine)-induced spinal cord DRG. The possible downstream target of EZH2 inhibition may interact with caspase and TrkC signaling pathways. human Nervous High+Lowthroughput Inhibiting EZH2 rescued bupivacaine-induced neuronal apoptosis in spinal cord dorsal root ganglia in mice 否 Other E_02_0313 Western blot,Quantitative real‑time polymerase chain reaction(qRT‑PCR),Caspase‑9 activity assay,TUNEL,siRNA EZH2 is upregulated, whereas inhibiting EZH2 exerted rescuing effect in anesthetics (bupivacaine)-induced spinal cord DRG. The possible downstream target of EZH2 inhibition may interact with caspase and TrkC signaling pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 is upregulated, whereas inhibiting EZH2 exerted rescuing effect in anesthetics (bupivacaine)-induced spinal cord DRG. The possible downstream target of EZH2 inhibition may interact with caspase and TrkC signaling pathways. Immunohistochemical staining EZH2 is upregulated, whereas inhibiting EZH2 exerted rescuing effect in anesthetics (bupivacaine)-induced spinal cord DRG. The possible downstream target of EZH2 inhibition may interact with caspase and TrkC signaling pathways. Western blot,Quantitative real‑time polymerase chain reaction(qRT‑PCR),Caspase‑9 activity assay,TUNEL,siRNA EZH2 EZH2 is upregulated, whereas inhibiting EZH2 exerted rescuing effect in anesthetics (bupivacaine)-induced spinal cord DRG. The possible downstream target of EZH2 inhibition may interact with caspase and TrkC signaling pathways. 29749505 chr1 52156183 52158183 Stat1 A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS. mouse lymphoid High+Lowthroughput Identification of genes and pathways associated with multiple organ dysfunction syndrome by microarray analysis 否 Multiple organ dysfunction syndrome (MODS) T lymphocyte E_02_0314 Pathway enrichment analysis A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS. Immunohistochemical staining A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS. Pathway enrichment analysis Stat1,Cebpb,Olfml1,Cxcl1,Cxcl10 A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS.;A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS.;A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS.;A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS.;A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein β (Cebpb) and olfactomedin‑like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS. 29734115 chr7 18083808 18085808 HDAC9 Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs. human lymphoid High+Lowthroughput Transcriptional and posttranscriptional repression of histone deacetylases by docosahexaenoic acid in macrophages 否 Other RAW 264.7 macrophages E_02_0315 HDAC9 knockdown by small interfering RNA (siRNA),RT-qPCR,Western blot, Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs. Immunohistochemical staining Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs. HDAC9 knockdown by small interfering RNA (siRNA),RT-qPCR,Western blot, HDAC9,HDAC1,HDAC3,HDAC2,HDAC4 Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs.;Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs.;Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs.;Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs.;Our results demonstrate that DHA represses the expression of HDAC3, 4 and 9 at the transcriptional or posttranscriptional levels in murine macrophages. This suggests that the anti-inflammatory effect of DHA may be mediated by the reduction of HDACs. 29731818 chr18 59217032 59219032 GRP Furthermore, levels of ERS-associated proteins, including caspase-3, activating transcription factor 6, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α, eukaryotic initiation factor 2 α and GRP78, were significantly increased following SCI; however, administration of MTX for 7 days significantly reversed this effect (P<0.05, P<0.01 and P<0.001). Therefore, MTX may improve SCI by suppressing ERS-induced apoptosis in vitro and in vivo. human connective High+Lowthroughput Methotrexate remediates spinal cord injury in vivo and in vitro via suppression of endoplasmic reticulum stress-induced apoptosis 否 Spinal cord injury (SCI) PC12 cell E_02_0316 Basso, Beattie and Bresnahan (BBB) scoring,MTT colorimetric assay,Western blot,Apoptosis assay,Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end (TUNEL),ELISA,flow cytometry, Furthermore, levels of ERS-associated proteins, including caspase-3, activating transcription factor 6, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α, eukaryotic initiation factor 2 α and GRP78, were significantly increased following SCI; however, administration of MTX for 7 days significantly reversed this effect (P<0.05, P<0.01 and P<0.001). Therefore, MTX may improve SCI by suppressing ERS-induced apoptosis in vitro and in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, levels of ERS-associated proteins, including caspase-3, activating transcription factor 6, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α, eukaryotic initiation factor 2 α and GRP78, were significantly increased following SCI; however, administration of MTX for 7 days significantly reversed this effect (P<0.05, P<0.01 and P<0.001). Therefore, MTX may improve SCI by suppressing ERS-induced apoptosis in vitro and in vivo. Immunohistochemical staining Furthermore, levels of ERS-associated proteins, including caspase-3, activating transcription factor 6, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α, eukaryotic initiation factor 2 α and GRP78, were significantly increased following SCI; however, administration of MTX for 7 days significantly reversed this effect (P<0.05, P<0.01 and P<0.001). Therefore, MTX may improve SCI by suppressing ERS-induced apoptosis in vitro and in vivo. Basso, Beattie and Bresnahan (BBB) scoring,MTT colorimetric assay,Western blot,Apoptosis assay,Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end (TUNEL),ELISA,flow cytometry, GRP Furthermore, levels of ERS-associated proteins, including caspase-3, activating transcription factor 6, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α, eukaryotic initiation factor 2 α and GRP78, were significantly increased following SCI; however, administration of MTX for 7 days significantly reversed this effect (P<0.05, P<0.01 and P<0.001). Therefore, MTX may improve SCI by suppressing ERS-induced apoptosis in vitro and in vivo. 29729398 chr13 15635141 15637141 Gli3 Absent anterior skeletal elements in the Ezh2 mutant background were not rescued by either reduction of Gli activator or forced expression of Gli repressor. The data imply that Ezh2 is epistatic to Gli3 and suggest the possibility that hedghehog activation is repressed by the recruitment of polycomb repressive complex 2. mouse / High+Lowthroughput Genetic interaction between Gli3 and Ezh2 during limb pattern formation 否 Other E_02_0317 Whole mount in situ hybridisation,staining, Absent anterior skeletal elements in the Ezh2 mutant background were not rescued by either reduction of Gli activator or forced expression of Gli repressor. The data imply that Ezh2 is epistatic to Gli3 and suggest the possibility that hedghehog activation is repressed by the recruitment of polycomb repressive complex 2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Absent anterior skeletal elements in the Ezh2 mutant background were not rescued by either reduction of Gli activator or forced expression of Gli repressor. The data imply that Ezh2 is epistatic to Gli3 and suggest the possibility that hedghehog activation is repressed by the recruitment of polycomb repressive complex 2. Immunohistochemical staining Absent anterior skeletal elements in the Ezh2 mutant background were not rescued by either reduction of Gli activator or forced expression of Gli repressor. The data imply that Ezh2 is epistatic to Gli3 and suggest the possibility that hedghehog activation is repressed by the recruitment of polycomb repressive complex 2. Whole mount in situ hybridisation,staining, Gli3,Ezh2 Absent anterior skeletal elements in the Ezh2 mutant background were not rescued by either reduction of Gli activator or forced expression of Gli repressor. The data imply that Ezh2 is epistatic to Gli3 and suggest the possibility that hedghehog activation is repressed by the recruitment of polycomb repressive complex 2.;Absent anterior skeletal elements in the Ezh2 mutant background were not rescued by either reduction of Gli activator or forced expression of Gli repressor. The data imply that Ezh2 is epistatic to Gli3 and suggest the possibility that hedghehog activation is repressed by the recruitment of polycomb repressive complex 2. 29718709 chr5 75333700 75335700 HMGCR The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. human High+Lowthroughput Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring 否 Hypercholesterolemia L02 E_02_0318 small interfering RNA,ELISA, quantitative RT-PCR,Sulforhodamine B assay,Chromatin immunoprecipitation assay,Western blot, The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. Immunohistochemical staining The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. small interfering RNA,ELISA, quantitative RT-PCR,Sulforhodamine B assay,Chromatin immunoprecipitation assay,Western blot, HMGCR,GC The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR.;The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. 29716548 chr6 3220562 3222562 TUBB2B Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations. human High+Lowthroughput A genome-wide assessment of conserved SNP alleles reveals a panel of regulatory SNPs relevant to the peripheral nerve 是 Neuropathy immortalized rat Schwann (S16) cell E_02_0319 PCR,transfection,TRANSFAC analysis,CRISPR/Cas9,RNA-Seq,RT-PCR,Digital droplet PCR,transgenic mice,Cap analysis gene expression (CAGE),ChIP-Seq, Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations. Immunohistochemical staining Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations. PCR,transfection,TRANSFAC analysis,CRISPR/Cas9,RNA-Seq,RT-PCR,Digital droplet PCR,transgenic mice,Cap analysis gene expression (CAGE),ChIP-Seq, TUBB2B,SOX10 Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations.;Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations. 29712641 chr1 32289831 32291831 HDAC1 Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles. human High+Lowthroughput Histone deacetylases 1 and 2 regulate the transcriptional programs of nephron progenitors and renal vesicles 否 NPC, kidney development 293T cell E_02_0320 ChIP-PCR,droplet digital PCR (ddPCR),qPCR,RT-qPCR,PCR,Chromatin Immunoprecipitation (ChIP),Immunoprecipitation,Western blot,transfection,TUNEL Assay,Section in situ hybridization (ISH),Histology, immunohistochemistry,Genome-wide microarray analysis,transgenic mice, Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles. Immunohistochemical staining Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles. ChIP-PCR,droplet digital PCR (ddPCR),qPCR,RT-qPCR,PCR,Chromatin Immunoprecipitation (ChIP),Immunoprecipitation,Western blot,transfection,TUNEL Assay,Section in situ hybridization (ISH),Histology, immunohistochemistry,Genome-wide microarray analysis,transgenic mice, HDAC1,HDAC2,Six2,Osr1,Sall1,Lhx1,Dll1,Trp53 Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles.;Here, we report that NPC-specific deletion of Hdac1 and Hdac2 genes in mice results in early postnatal lethality owing to renal hypodysplasia and loss of NPCs. HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer. Although the mutant NPCs differentiate into renal vesicles (RVs), Hdac1/2 mutant kidneys lack nascent nephrons or mature glomeruli, a phenocopy of Lhx1 mutants. Transcriptional profiling and network analysis identified disrupted expression of Lhx1 and its downstream genes, Dll1 and Hnf1a/4a, as key mediators of the renal phenotype. Finally, although HDAC1/2-deficient NPCs and RVs overexpress hyperacetylated p53, Trp53 deletion failed to rescue the renal dysgenesis. We conclude that the epigenetic regulators HDAC1 and HDAC2 control nephrogenesis via interactions with the transcriptional programs of nephron progenitors and renal vesicles. 29710033 chr10 88951091 88953091 FAS CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK. human adipose High+Lowthroughput Methylxanthine Derivative-Rich Cacao Extract Suppresses Differentiation of Adipocytes through Downregulation of PPARγ and C/EBPs 否 Obesity 3T3-L1 preadipocytes E_02_0321 Western blot,qPCR,Immunofluorescence,crystal violet staining assays,sudan II staining, CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK. Immunohistochemical staining CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK. Western blot,qPCR,Immunofluorescence,crystal violet staining assays,sudan II staining, FAS CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK. 29706059 chr5 372500 376000 HOXA5 Our findings suggest that AHRR SM-DMR up-regulates AHRR mRNA in a monocyte-specific manner by activating the AHRR enhancer. Cell type-specific activation of enhancers at SM-DMRs may represent a mechanism driving smoking-related disease. human Low+High throughput Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type-Specific Enhancer Activation and Gene Expression 是 Cardiovascular Cancer CD14+ cell E_02_0322 ChIP-seq,RNA-seq We tested total RNA samples from a group of CRU-mRNA with available RNA (n=11smokers/10 nonsmokers) and observed three ofthe SM-DMR locations(AHRR, C5orf55-EXOC-AS, and SASH1) showedup-regulation of correspondinge RNA expression as well as mRNA. Enhancer -- RT-PCR AHH,AHHR,bHLHe77 -- -- -- -- -- -- -- AHRR,AHRR,AHRR,AHRR,AHRR,AHRR,AHRR,AHRR,AHRR --,--,--,--,--,--,--,--,-- The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region.;The Figure6C bar graph displays the significants moking-associated fold-change results for each RT-qPCR relative to their genome position in the AHRR region. --;--;--;--;--;--;--;--;-- 29695955 chr1 231623949 231625949 DISC1 Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. human Nervous High+Lowthroughput GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1 否 Schizophrenia type 1 disorder, schizophrenia E_02_0323 Western Blot,Immunohistochemistry Analysis, Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. Immunohistochemical staining Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. Western Blot,Immunohistochemistry Analysis, DISC1 Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. 29695788 chr6 31137269 31137697 TFAP2C To identify new transcription factors that differentially regulate the unique pluripotent stages, we mapped open chromatin using ATAC-seq and found enrichment of the activator protein-2 (AP2) transcription factor binding motif at naive-specific open chromatin. We determined that the AP2 family member TFAP2C is upregulated during primed to naive reversion and becomes widespread at naive-specific enhancers. TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naive by facilitating the opening of enhancers proximal to pluripotency factors. Additionally, we identify a previously undiscovered naive-specific POU5F1 (OCT4) enhancer enriched for TFAP2C binding. Taken together, TFAP2C establishes and maintains naive human pluripotency and regulates OCT4 expression by mechanisms that are distinct from mouse. human Low+High throughput TFAP2C regulates transcription in human naive pluripotency by opening enhancers 否 -- embryonic stem cell E_02_0324 ATAC-seq,Luciferase Reporter Assay,ChIP-seq In human pre-implantation blastocyst, however, neither enhancer appears open, whereas two putative enhancers appear downstream of the POU5F1 TSS. Each of these peaks contains a cluster of AP2 sites and a KLF site, indicating that they could be opened by the combinatorial activity of these transcription factors during preimplantation development. Enhancer CRISPR/Cas9 -- OCT3, OCT4, OTF-3, OTF3, OTF4, Oct-3, Oct-4 TFAP2C functions to maintain pluripotency and repress neuroectodermal differentiation during the transition from primed to naive by facilitating the opening of enhancers proximal to pluripotency factors. Luciferase Reporter Assay,CRISPR/Cas9 This indicates a potential direct role for TFAP2C in regulating the pluripotency master-regulator OCT4 by binding to a previously unknown Enhancer, which in turn is likely to be important for preimplantation OCT4 expression. AP2-GAMMA,ERF1,TFAP2G,hAP-2g Luciferase Reporter Assay -- -- POU5F1,POU5F1 TFAP2C,TFAP2C We found normal expression of OCT4 and self-renewal in the primed state, but a dramatic loss of OCT4 expression accompanied by differentiation upon reversion to the naive state. This indicates a potential direct role for TFAP2C in regulating the pluripotency master-regulator OCT4 by binding to a previously unknown enhancer, which in turn is likely to be important for preimplantation OCT4 expression.;We found normal expression of OCT4 and self-renewal in the primed state, but a dramatic loss of OCT4 expression accompanied by differentiation upon reversion to the naive state. This indicates a potential direct role for TFAP2C in regulating the pluripotency master-regulator OCT4 by binding to a previously unknown enhancer, which in turn is likely to be important for preimplantation OCT4 expression. Luciferase activity from a pGL3 construct in which WT or mutant Intron Element 1 had been cloned, normalized to signal from a pGL3 construct with no enhancer. Results are shown from two independent experiment, except for the ΔAP2 sample, for which there are n=3 replicates from two experiments. All signals were first normalized for Renilla signal.;Luciferase activity from a pGL3 construct in which WT or mutant Intron Element 1 had been cloned, normalized to signal from a pGL3 construct with no enhancer. Results are shown from two independent experiment, except for the ΔAP2 sample, for which there are n=3 replicates from two experiments. All signals were first normalized for Renilla signal. 29691190 chr11 2161549 2163549 TH NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. human lymphoid High+Lowthroughput Noni (Morinda citrifolia L.) fruit juice delays immunosenescence in the lymphocytes in lymph nodes of old F344 rats 否 Immunosenescence, inflammation lymphocyte E_02_0325 MTT assays,Western blot,NO production,Assays for antioxidant enzymes,assays for lipid peroxidation,ELISA, NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. Immunohistochemical staining NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. MTT assays,Western blot,NO production,Assays for antioxidant enzymes,assays for lipid peroxidation,ELISA, TH NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50. 29689351 chr17 42310380 42312380 STAT3 GFE inhibits lipogenesis by negative regulation of adipogenic transcription factors, which is associated with GFE-mediated cell cycle arrest and STAT3 inhibition. human adipose High+Lowthroughput The fruits of Gleditsia sinensis Lam. inhibits adipogenesis through modulation of mitotic clonal expansion and STAT3 activation in 3T3-L1 cells 否 Neoplasms, thrombosis, inflammation related disorders, obesity 3T3-L1 cell E_02_0326 MTT,Oil Red O staining,crystal violet staining,flow cytometry,ELISA,Quantitative Real-time PCR, Immunofluorescence,western blot,Immunoblotting, GFE inhibits lipogenesis by negative regulation of adipogenic transcription factors, which is associated with GFE-mediated cell cycle arrest and STAT3 inhibition. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GFE inhibits lipogenesis by negative regulation of adipogenic transcription factors, which is associated with GFE-mediated cell cycle arrest and STAT3 inhibition. Immunohistochemical staining GFE inhibits lipogenesis by negative regulation of adipogenic transcription factors, which is associated with GFE-mediated cell cycle arrest and STAT3 inhibition. MTT,Oil Red O staining,crystal violet staining,flow cytometry,ELISA,Quantitative Real-time PCR, Immunofluorescence,western blot,Immunoblotting, STAT3 GFE inhibits lipogenesis by negative regulation of adipogenic transcription factors, which is associated with GFE-mediated cell cycle arrest and STAT3 inhibition. 32161797 chr1 51574533 51576533 OSBPL9 OSBPL9 is a novel ER stress-responsive gene and we confirmed that endogenous mRNA expression of OSBPL9 is upregulated by thapsigargin, and is repressed by IRE1α inhibitors, 4μ8C and toyocamycin, but not significantly by a PERK inhibitor, GSK2656157. These results demonstrate that this approach can be used to discover novel genes regulated by any stimuli without the need for microarray analysis, and that it can concomitantly produce reporter cells without identification of stimuli-responsive promoter/enhancer elements. Therefore, this system has a variety of benefits for basic and clinical research. human High+Lowthroughput A highly sensitive trap vector system for isolating reporter cells and identification of responsive genes 否 Other NMuMG cell E_02_0327 Luciferase assay,Immunoblotting,Real-time PCR,Splinkerette PCR,Fluorescence-activated cell sorting,transfection, OSBPL9 is a novel ER stress-responsive gene and we confirmed that endogenous mRNA expression of OSBPL9 is upregulated by thapsigargin, and is repressed by IRE1α inhibitors, 4μ8C and toyocamycin, but not significantly by a PERK inhibitor, GSK2656157. These results demonstrate that this approach can be used to discover novel genes regulated by any stimuli without the need for microarray analysis, and that it can concomitantly produce reporter cells without identification of stimuli-responsive promoter/enhancer elements. Therefore, this system has a variety of benefits for basic and clinical research. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq OSBPL9 is a novel ER stress-responsive gene and we confirmed that endogenous mRNA expression of OSBPL9 is upregulated by thapsigargin, and is repressed by IRE1α inhibitors, 4μ8C and toyocamycin, but not significantly by a PERK inhibitor, GSK2656157. These results demonstrate that this approach can be used to discover novel genes regulated by any stimuli without the need for microarray analysis, and that it can concomitantly produce reporter cells without identification of stimuli-responsive promoter/enhancer elements. Therefore, this system has a variety of benefits for basic and clinical research. Immunohistochemical staining OSBPL9 is a novel ER stress-responsive gene and we confirmed that endogenous mRNA expression of OSBPL9 is upregulated by thapsigargin, and is repressed by IRE1α inhibitors, 4μ8C and toyocamycin, but not significantly by a PERK inhibitor, GSK2656157. These results demonstrate that this approach can be used to discover novel genes regulated by any stimuli without the need for microarray analysis, and that it can concomitantly produce reporter cells without identification of stimuli-responsive promoter/enhancer elements. Therefore, this system has a variety of benefits for basic and clinical research. Luciferase assay,Immunoblotting,Real-time PCR,Splinkerette PCR,Fluorescence-activated cell sorting,transfection, OSBPL9,MYC OSBPL9 is a novel ER stress-responsive gene and we confirmed that endogenous mRNA expression of OSBPL9 is upregulated by thapsigargin, and is repressed by IRE1α inhibitors, 4μ8C and toyocamycin, but not significantly by a PERK inhibitor, GSK2656157. These results demonstrate that this approach can be used to discover novel genes regulated by any stimuli without the need for microarray analysis, and that it can concomitantly produce reporter cells without identification of stimuli-responsive promoter/enhancer elements. Therefore, this system has a variety of benefits for basic and clinical research.;OSBPL9 is a novel ER stress-responsive gene and we confirmed that endogenous mRNA expression of OSBPL9 is upregulated by thapsigargin, and is repressed by IRE1α inhibitors, 4μ8C and toyocamycin, but not significantly by a PERK inhibitor, GSK2656157. These results demonstrate that this approach can be used to discover novel genes regulated by any stimuli without the need for microarray analysis, and that it can concomitantly produce reporter cells without identification of stimuli-responsive promoter/enhancer elements. Therefore, this system has a variety of benefits for basic and clinical research. 29684535 chr1 45691360 45693360 IPP In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability. human High+Lowthroughput Sodium caprate enables the blood pressure-lowering effect of Ile-Pro-Pro and Leu-Lys-Pro in spontaneously hypertensive rats by indirectly overcoming PepT1 inhibition 否 Other Caco-2 cell E_02_0328 Immunofluorescence, Histology,In vivo rat studies, In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability. Immunohistochemical staining In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability. Immunofluorescence, Histology,In vivo rat studies, IPP,ACE In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability.;In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability. 29683870 chr4 153680698 153682698 TLR2 Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI. human / High+Lowthroughput Isosteviol sodium injection improves outcomes by modulating TLRs/NF-κB-dependent inflammatory responses following experimental traumatic brain injury in rats 否 inflammatory reaction E_02_0329 Nissl staining,Immunohistochemical assays,qRT-PCR,Enzyme-linked immunosorbent assay(ELISA),Western blot, Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI. Immunohistochemical staining Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI. Nissl staining,Immunohistochemical assays,qRT-PCR,Enzyme-linked immunosorbent assay(ELISA),Western blot, TLR2,TLR4,GFAP Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI.;Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI.;Results from quantitative real-time-PCR and western blotting also show that the mRNA and protein expression levels of TLR2, TLR4, and NF-κB were significantly lower in STVNa-treated rats compared with the vehicle-treated rats. The administration of STVNa attenuates the TLR/NF-κB signaling pathway-mediated inflammatory responses in the injured rat brain, and this may be the mechanism by which STVNa improves the outcome following TBI. 29683207 chrX 103771498 103773498 PLP1 These results demonstrate for the first time that the wmN1 enhancer region: (1) is functional in hPLP1; (2) works in collaboration with its native promoter-not just a basal heterologous promoter; (3) is required for high levels of hPLP1 gene activity; (4) has a broader effect, both spatially and temporally, than originally projected with mPlp1. human High+Lowthroughput The wmN1 enhancer region in intron 1 is required for expression of human PLP1 否 Human X-linked inherited disorders Oli-neu cell E_02_0330 Transgenic mice,qRT-PCR, b-galactosidase histochemistry,b-galactosidase enzyme assay,Combined X-gal staining,immunohistochemistry,Southern blot, These results demonstrate for the first time that the wmN1 enhancer region: (1) is functional in hPLP1; (2) works in collaboration with its native promoter-not just a basal heterologous promoter; (3) is required for high levels of hPLP1 gene activity; (4) has a broader effect, both spatially and temporally, than originally projected with mPlp1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results demonstrate for the first time that the wmN1 enhancer region: (1) is functional in hPLP1; (2) works in collaboration with its native promoter-not just a basal heterologous promoter; (3) is required for high levels of hPLP1 gene activity; (4) has a broader effect, both spatially and temporally, than originally projected with mPlp1. Immunohistochemical staining These results demonstrate for the first time that the wmN1 enhancer region: (1) is functional in hPLP1; (2) works in collaboration with its native promoter-not just a basal heterologous promoter; (3) is required for high levels of hPLP1 gene activity; (4) has a broader effect, both spatially and temporally, than originally projected with mPlp1. Transgenic mice,qRT-PCR, b-galactosidase histochemistry,b-galactosidase enzyme assay,Combined X-gal staining,immunohistochemistry,Southern blot, PLP1 These results demonstrate for the first time that the wmN1 enhancer region: (1) is functional in hPLP1; (2) works in collaboration with its native promoter-not just a basal heterologous promoter; (3) is required for high levels of hPLP1 gene activity; (4) has a broader effect, both spatially and temporally, than originally projected with mPlp1. 29680697 chr16 29880079 29882079 Hes1 Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo. mouse High+Lowthroughput Regeneration of Cochlear Hair Cells and Hearing Recovery through Hes1 Modulation with siRNA Nanoparticles in Adult Guinea Pigs 否 Acute acoustic trauma E_02_0331 RT-qPCR,Auditory brainstem response (ABR) measurements,siRNA,Immunohistology,Scanning electron microscopy, Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo. Immunohistochemical staining Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo. RT-qPCR,Auditory brainstem response (ABR) measurements,siRNA,Immunohistology,Scanning electron microscopy, Hes1 Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo. 29678838 chr17 34252627 34254627 CCL2 Treatment of human retinal Müller cells with high-glucose induced significant upregulation of ROCK-1, VEGF, and MCP-1/CCL2. Fasudil co-treatment normalized the high-glucose-induced upregulation of these mediators. Similarly, fasudil attenuated high-glucose-induced enhanced immunoreactivity for ROCK-1 and VEGF. Diabetes induced upregulation of ROCK-1, p-ERK ½, p-NF-κB and iNOS expression in retinas of mice. Constant fasudil intake from the onset of diabetes did not affect the metabolic status of diabetic mice but it attenuated diabetes-induced upregulation of these inflammatory signaling pathways.Our finding suggests that Rho-associated protein kinase-1 activation mediates regulation of inflammatory signaling pathways in diabetic retina. human Nervous High+Lowthroughput Rho-Associated Protein Kinase-1 Mediates the Regulation of Inflammatory Markers in Diabetic Retina and in Retinal Müller Cells 否 Diabetic retinopathy, inflammation MIO-M1 cell E_02_0332 Enzyme-linked immunosorbent assay(ELISA),Western blot,Immunofluorescence, Treatment of human retinal Müller cells with high-glucose induced significant upregulation of ROCK-1, VEGF, and MCP-1/CCL2. Fasudil co-treatment normalized the high-glucose-induced upregulation of these mediators. Similarly, fasudil attenuated high-glucose-induced enhanced immunoreactivity for ROCK-1 and VEGF. Diabetes induced upregulation of ROCK-1, p-ERK ½, p-NF-κB and iNOS expression in retinas of mice. Constant fasudil intake from the onset of diabetes did not affect the metabolic status of diabetic mice but it attenuated diabetes-induced upregulation of these inflammatory signaling pathways.Our finding suggests that Rho-associated protein kinase-1 activation mediates regulation of inflammatory signaling pathways in diabetic retina. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Treatment of human retinal Müller cells with high-glucose induced significant upregulation of ROCK-1, VEGF, and MCP-1/CCL2. Fasudil co-treatment normalized the high-glucose-induced upregulation of these mediators. Similarly, fasudil attenuated high-glucose-induced enhanced immunoreactivity for ROCK-1 and VEGF. Diabetes induced upregulation of ROCK-1, p-ERK ½, p-NF-κB and iNOS expression in retinas of mice. Constant fasudil intake from the onset of diabetes did not affect the metabolic status of diabetic mice but it attenuated diabetes-induced upregulation of these inflammatory signaling pathways.Our finding suggests that Rho-associated protein kinase-1 activation mediates regulation of inflammatory signaling pathways in diabetic retina. Immunohistochemical staining Treatment of human retinal Müller cells with high-glucose induced significant upregulation of ROCK-1, VEGF, and MCP-1/CCL2. Fasudil co-treatment normalized the high-glucose-induced upregulation of these mediators. Similarly, fasudil attenuated high-glucose-induced enhanced immunoreactivity for ROCK-1 and VEGF. Diabetes induced upregulation of ROCK-1, p-ERK ½, p-NF-κB and iNOS expression in retinas of mice. Constant fasudil intake from the onset of diabetes did not affect the metabolic status of diabetic mice but it attenuated diabetes-induced upregulation of these inflammatory signaling pathways.Our finding suggests that Rho-associated protein kinase-1 activation mediates regulation of inflammatory signaling pathways in diabetic retina. Enzyme-linked immunosorbent assay(ELISA),Western blot,Immunofluorescence, CCL2,Rho Treatment of human retinal Müller cells with high-glucose induced significant upregulation of ROCK-1, VEGF, and MCP-1/CCL2. Fasudil co-treatment normalized the high-glucose-induced upregulation of these mediators. Similarly, fasudil attenuated high-glucose-induced enhanced immunoreactivity for ROCK-1 and VEGF. Diabetes induced upregulation of ROCK-1, p-ERK ½, p-NF-κB and iNOS expression in retinas of mice. Constant fasudil intake from the onset of diabetes did not affect the metabolic status of diabetic mice but it attenuated diabetes-induced upregulation of these inflammatory signaling pathways.Our finding suggests that Rho-associated protein kinase-1 activation mediates regulation of inflammatory signaling pathways in diabetic retina.;Treatment of human retinal Müller cells with high-glucose induced significant upregulation of ROCK-1, VEGF, and MCP-1/CCL2. Fasudil co-treatment normalized the high-glucose-induced upregulation of these mediators. Similarly, fasudil attenuated high-glucose-induced enhanced immunoreactivity for ROCK-1 and VEGF. Diabetes induced upregulation of ROCK-1, p-ERK ½, p-NF-κB and iNOS expression in retinas of mice. Constant fasudil intake from the onset of diabetes did not affect the metabolic status of diabetic mice but it attenuated diabetes-induced upregulation of these inflammatory signaling pathways.Our finding suggests that Rho-associated protein kinase-1 activation mediates regulation of inflammatory signaling pathways in diabetic retina. 29676032 chr12 6784508 6786508 CD4 Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs. human High+Lowthroughput Use of two gRNAs for CRISPR/Cas9 improves bi-allelic homologous recombination efficiency in mouse embryonic stem cells 否 Other E_02_0333 CRISPR/Cas9,transfection,Immunofluorescence,PCR,Flow Cytometry,T7E1 cleavage assay, Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs. Immunohistochemical staining Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs. CRISPR/Cas9,transfection,Immunofluorescence,PCR,Flow Cytometry,T7E1 cleavage assay, CD4,Rax,HR Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs.;Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs.;Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs. The bi-allelic recombination targeting efficiency is over 90% when using two gRNAs together with the inhibition of non-homologous end-joint repair. Moreover, this technique is compatible with the generation of knocked-in mice and the use of ESC-derived differentiation protocols, therefore facilitating and accelerating the gene targeting in mice and ESCs. 29673286 chr9 117701285 117703285 TLR4 Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment. human High+Lowthroughput Inhibition of autophagy with 3-methyladenine is protective in a lethal model of murine endotoxemia and polymicrobial sepsis 否 Endotoxic shock E_02_0334 ELISA,immunohistochemical analysis,Western blot, Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment. Immunohistochemical staining Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment. ELISA,immunohistochemical analysis,Western blot, TLR4 Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment. 29669761 chr2 29190441 29192441 ALK Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449,another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy. human High+Lowthroughput Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors 否 Positive lung cancer H3122 cell E_02_0335 transgenic mice,ChIP-seq,RNA-seq,small RNA-seq,microarray analysis,qRT-PCR,western blot,immunohistochemical staining, Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449,another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449,another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy. Immunohistochemical staining Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449,another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy. transgenic mice,ChIP-seq,RNA-seq,small RNA-seq,microarray analysis,qRT-PCR,western blot,immunohistochemical staining, ALK Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449,another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy. 29662163 chr2 221415351 221417351 EPHA4 Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs. human High+Lowthroughput Polymer physics predicts the effects of structural variants on chromatin architecture 否 Structural variation (SV) CH12-LX cell E_02_0336 The PRISMR algorithm,Analyses of the model binding domains,Hi-C,cHi-C, Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs. Immunohistochemical staining Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs. The PRISMR algorithm,Analyses of the model binding domains,Hi-C,cHi-C, EPHA4,CTCF Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs.;Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs. 29654753 chr6 47504283 47506283 Ezh2 We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo. mouse adipose High+Lowthroughput GSK126 alleviates the obesity phenotype by promoting the differentiation of thermogenic beige adipocytes in diet-induced obese mice 否 Obesity beige adipocytes E_02_0337 Western blot,ELISAs,RT-qPCR, Immunohistochemistry,Histological analysis, We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo. Immunohistochemical staining We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo. Western blot,ELISAs,RT-qPCR, Immunohistochemistry,Histological analysis, Ezh2 We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo. 29648668 chr20 22578409 22580409 FOXA2 Conditional uterine deletion of ERα, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the majority of DES-mediated changes in gene expression and H3K27ac signal at target enhancers. An ERα dependent super-enhancer was located at the Padi gene locus and a topological connection to the Padi1 TSS was documented using 3C-PCR. Chromosome looping at this site was independent of ERα and DES exposure, indicating that the interaction is established prior to ligand signaling. However, enrichment of H3K27ac and transcriptional activation at this locus was both DES and ERα-dependent. These data suggest that DES alters uterine development and consequently adult reproductive function by modifying the enhancer landscape at ERα binding sites near estrogen-regulated genes. human High+Lowthroughput Widespread enhancer activation via ERα mediates estrogen response in vivo during uterine development 否 Other ES cell E_02_0338 RNA-seq,microarray analysis,PCR,real time RT-PCR,RNA isolation,Chromatin immunoprecipitation for analysis,Histone purification,immunoblotting,Chromatin conformation capture assay (3C PCR),ChIP-seq, Conditional uterine deletion of ERα, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the majority of DES-mediated changes in gene expression and H3K27ac signal at target enhancers. An ERα dependent super-enhancer was located at the Padi gene locus and a topological connection to the Padi1 TSS was documented using 3C-PCR. Chromosome looping at this site was independent of ERα and DES exposure, indicating that the interaction is established prior to ligand signaling. However, enrichment of H3K27ac and transcriptional activation at this locus was both DES and ERα-dependent. These data suggest that DES alters uterine development and consequently adult reproductive function by modifying the enhancer landscape at ERα binding sites near estrogen-regulated genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conditional uterine deletion of ERα, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the majority of DES-mediated changes in gene expression and H3K27ac signal at target enhancers. An ERα dependent super-enhancer was located at the Padi gene locus and a topological connection to the Padi1 TSS was documented using 3C-PCR. Chromosome looping at this site was independent of ERα and DES exposure, indicating that the interaction is established prior to ligand signaling. However, enrichment of H3K27ac and transcriptional activation at this locus was both DES and ERα-dependent. These data suggest that DES alters uterine development and consequently adult reproductive function by modifying the enhancer landscape at ERα binding sites near estrogen-regulated genes. Immunohistochemical staining Conditional uterine deletion of ERα, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the majority of DES-mediated changes in gene expression and H3K27ac signal at target enhancers. An ERα dependent super-enhancer was located at the Padi gene locus and a topological connection to the Padi1 TSS was documented using 3C-PCR. Chromosome looping at this site was independent of ERα and DES exposure, indicating that the interaction is established prior to ligand signaling. However, enrichment of H3K27ac and transcriptional activation at this locus was both DES and ERα-dependent. These data suggest that DES alters uterine development and consequently adult reproductive function by modifying the enhancer landscape at ERα binding sites near estrogen-regulated genes. RNA-seq,microarray analysis,PCR,real time RT-PCR,RNA isolation,Chromatin immunoprecipitation for analysis,Histone purification,immunoblotting,Chromatin conformation capture assay (3C PCR),ChIP-seq, FOXA2,FOXO1 Conditional uterine deletion of ERα, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the majority of DES-mediated changes in gene expression and H3K27ac signal at target enhancers. An ERα dependent super-enhancer was located at the Padi gene locus and a topological connection to the Padi1 TSS was documented using 3C-PCR. Chromosome looping at this site was independent of ERα and DES exposure, indicating that the interaction is established prior to ligand signaling. However, enrichment of H3K27ac and transcriptional activation at this locus was both DES and ERα-dependent. These data suggest that DES alters uterine development and consequently adult reproductive function by modifying the enhancer landscape at ERα binding sites near estrogen-regulated genes.;Conditional uterine deletion of ERα, but not the pioneer transcription factors FOXA2 or FOXO1, prevented the majority of DES-mediated changes in gene expression and H3K27ac signal at target enhancers. An ERα dependent super-enhancer was located at the Padi gene locus and a topological connection to the Padi1 TSS was documented using 3C-PCR. Chromosome looping at this site was independent of ERα and DES exposure, indicating that the interaction is established prior to ligand signaling. However, enrichment of H3K27ac and transcriptional activation at this locus was both DES and ERα-dependent. These data suggest that DES alters uterine development and consequently adult reproductive function by modifying the enhancer landscape at ERα binding sites near estrogen-regulated genes. 29648621 chr19 45766891 45768891 DMPK Our data indicate that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in sarcomeric gene expression by interfering with SRF transcriptional activity. Together, these results demonstrate an unexpected role for DMPK as a direct mediator of adverse cardiomyocyte remodelling and heart failure. human High+Lowthroughput The MEF2 transcriptional target DMPK induces loss of sarcomere structure and cardiomyopathy 否 heart failure NRCM cell E_02_0339 transfection,Gene expression profiling,Immunofluorescence,confocal microscopy,Histology,Electron microscopy,Western blot,Reverse-transcription PCR,Real-Time PCR,Chromatin immunoprecipitation, Our data indicate that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in sarcomeric gene expression by interfering with SRF transcriptional activity. Together, these results demonstrate an unexpected role for DMPK as a direct mediator of adverse cardiomyocyte remodelling and heart failure. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data indicate that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in sarcomeric gene expression by interfering with SRF transcriptional activity. Together, these results demonstrate an unexpected role for DMPK as a direct mediator of adverse cardiomyocyte remodelling and heart failure. Immunohistochemical staining Our data indicate that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in sarcomeric gene expression by interfering with SRF transcriptional activity. Together, these results demonstrate an unexpected role for DMPK as a direct mediator of adverse cardiomyocyte remodelling and heart failure. transfection,Gene expression profiling,Immunofluorescence,confocal microscopy,Histology,Electron microscopy,Western blot,Reverse-transcription PCR,Real-Time PCR,Chromatin immunoprecipitation, DMPK,SRF Our data indicate that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in sarcomeric gene expression by interfering with SRF transcriptional activity. Together, these results demonstrate an unexpected role for DMPK as a direct mediator of adverse cardiomyocyte remodelling and heart failure.;Our data indicate that MEF2-induced loss of sarcomeres is mediated by DMPK via a decrease in sarcomeric gene expression by interfering with SRF transcriptional activity. Together, these results demonstrate an unexpected role for DMPK as a direct mediator of adverse cardiomyocyte remodelling and heart failure. 29641996 chr8 128206162 128314310 CTCF We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. human Low+High throughput Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism 否 -- K562 cell E_02_0340 4C,ChIP-seq Among the DNA loop structures observed in these datasets, a large 2.8 Mb DNA loop was evident in all four cell types. This loop connects CTCF sites encompassing the MYC gene and qualifies as an insulated neighborhood. The DNA anchor sites of this 2.8 Mb DNA loop occur at the boundaries of a TAD found in all cells. Super-Enhancer CRISPR/Cas9 ChIA-PET,ChIP-qPCR MRTL,MYCC,bHLHe39,c-Myc The CTCF site in the promoter-proximal region of MYC is important for optimal interaction with distal Enhancers and supports the idea that this CTCF site functions as an Enhancer-docking site. 4C,CRISPR/Cas9,ChIP-qPCR Similar results were obtained in HCT-116 cells, where the viewpoint was centered on the super-Enhancer located -0.4 Mb upstream of the MYC gene MRD21 CRISPR/Cas9 -- -- MYC,MYC CTCF,CTCF CTCF chromatin immunoprecipitation quantative polymerase chain reaction (ChIP-qPCR) showed complete loss of CTCF binding to this site in K562 and HCT-116 cells and a 60%–70% reduction in CTCF binding at this site in Jurkat and MCF7 cells. RNA analysis revealed a 70%–80% reduction of endogenous MYC mRNA in the absence of the enhancer-docking site in all of these cell types.;CTCF chromatin immunoprecipitation quantative polymerase chain reaction (ChIP-qPCR) showed complete loss of CTCF binding to this site in K562 and HCT-116 cells and a 60%–70% reduction in CTCF binding at this site in Jurkat and MCF7 cells. RNA analysis revealed a 70%–80% reduction of endogenous MYC mRNA in the absence of the enhancer-docking site in all of these cell types. An inducible CRISPR/Cas9 perturbation model showed reduced proliferation for these four cell types upon induction of CTCF-site deletions .These results indicate that the CTCF motif in the MYC Enhancer-docking site is necessary for CTCF binding, for high levels of MYC expression and for cellular proliferation.;An inducible CRISPR/Cas9 perturbation model showed reduced proliferation for these four cell types upon induction of CTCF-site deletions .These results indicate that the CTCF motif in the MYC Enhancer-docking site is necessary for CTCF binding, for high levels of MYC expression and for cellular proliferation. 29637561 chr10 126881148 126883148 Cyp27b1 1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner. mouse High+Lowthroughput 1,25-dihydroxyvitamin D deficiency accelerates alveolar bone loss independent of aging and extracellular calcium and phosphorus 否 Periodontal disease CD3+ T cell E_02_0341 Computer-assisted Image Analysis,Quantitative Real-time PCR,Immunohistochemical Staining,Histochemical Staining,micro-computed tomography (micro-CT), 1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq 1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner. Immunohistochemical staining 1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner. Computer-assisted Image Analysis,Quantitative Real-time PCR,Immunohistochemical Staining,Histochemical Staining,micro-computed tomography (micro-CT), Cyp27b1,VDR,MMP3,MMP8 1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner.;1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner.;1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner.;1,25(OH)2 D deficiency in the 1α(OH)ase mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium- and phosphorus- as well as an age-independent manner. 32396940 chr11 32173084 32175084 Nprl3 Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. mouse High+Lowthroughput An evolutionarily ancient mechanism for regulation of hemoglobin expression in vertebrate red cells 否 Red blood cell (erythrocyte) E_02_0342 ATAC-seq,Nanopore sequencing Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. Immunohistochemical staining Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. ATAC-seq,Nanopore sequencing Nprl3 Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. 32617978 chr8 127732513 127734513 MYC Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. human connective High+Lowthroughput Targeting the KDM4B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate cancer 否 Prostate cancer CWR22Rv1 cell E_02_0343 RNA seq,ChIP assay,Immunohistochemistry, Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. Immunohistochemical staining Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. RNA seq,ChIP assay,Immunohistochemistry, MYC Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. 32617979 chr8 127732819 127734819 MYC Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K10 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. human connective High+Lowthroughput Targeting the KDM5B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate cancer 否 Prostate cancer LNCaP E_02_0344 RNA seq,ChIP assay,Immunohistochemistry, Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K10 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K10 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. Immunohistochemical staining Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K10 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. RNA seq,ChIP assay,Immunohistochemistry, MYC Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K10 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next generation AR-targeted therapy. 32392346 chr21 34784729 34786729 RUNX1 The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. human High+Lowthroughput Developmental trajectory of prehematopoietic stem cell formation from endothelium 否 IAC cell E_02_0345 scRNA-Seq，scATAC-Seq The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. Immunohistochemical staining The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. scRNA-Seq，scATAC-Seq RUNX1 The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. 32375045 chr4 56904890 56906890 REST we reveal the transcriptional repressor RE-1 silencing transcription factor (REST) as a barrier for b cell gene expression in the reprogramming of pancreatic exocrine cells. human High+Lowthroughput REST Inhibits Direct Reprogramming of Pancreatic Exocrine to Endocrine Cells by Preventing PDX1-Mediated Activation of Endocrine Genes 否 Diabetes endocrine cell E_02_0346 quantitative real-time PCR，Immunofluorescence，Flow cytometry，RNA-Seq，immunoprecipitation we reveal the transcriptional repressor RE-1 silencing transcription factor (REST) as a barrier for b cell gene expression in the reprogramming of pancreatic exocrine cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq we reveal the transcriptional repressor RE-1 silencing transcription factor (REST) as a barrier for b cell gene expression in the reprogramming of pancreatic exocrine cells. Immunohistochemical staining we reveal the transcriptional repressor RE-1 silencing transcription factor (REST) as a barrier for b cell gene expression in the reprogramming of pancreatic exocrine cells. quantitative real-time PCR，Immunofluorescence，Flow cytometry，RNA-Seq，immunoprecipitation REST we reveal the transcriptional repressor RE-1 silencing transcription factor (REST) as a barrier for b cell gene expression in the reprogramming of pancreatic exocrine cells. 32433819 chr19 17822384 17824384 JAK3 Moreover, using gainand loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. human High+Lowthroughput JAK3 restrains inflammatory responses and protects against periodontal disease through Wnt3a signaling 否 Periodontal disease THP-1 cells E_02_0347 Western blot,siRNA，Immunoprecipitation，RT-PCR Moreover, using gainand loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, using gainand loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. Immunohistochemical staining Moreover, using gainand loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. Western blot,siRNA，Immunoprecipitation，RT-PCR JAK3 Moreover, using gainand loss-of-function approaches, we demonstrate that downstream molecules of Wnt3a signaling, including Dvl3 and β-catenin, are responsible for the negative regulatory role of Wnt3a. 32461639 chrX 7437073 7439073 Foxp3 IsoDCA-producing consortia increased the number of colonic RORγt-expressing Treg cells in a CNS1-dependent manner, suggesting enhanced extrathymic diferentiation. mouse lymphoid High+Lowthroughput Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells 否 T cell E_02_0348 RNA-seq，Luciferase assays IsoDCA-producing consortia increased the number of colonic RORγt-expressing Treg cells in a CNS1-dependent manner, suggesting enhanced extrathymic diferentiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq IsoDCA-producing consortia increased the number of colonic RORγt-expressing Treg cells in a CNS1-dependent manner, suggesting enhanced extrathymic diferentiation. Immunohistochemical staining IsoDCA-producing consortia increased the number of colonic RORγt-expressing Treg cells in a CNS1-dependent manner, suggesting enhanced extrathymic diferentiation. RNA-seq，Luciferase assays Foxp3 IsoDCA-producing consortia increased the number of colonic RORγt-expressing Treg cells in a CNS1-dependent manner, suggesting enhanced extrathymic diferentiation. 32474518 chr7 148804991 148806991 EZH2 LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. human High+Lowthroughput Targeting EZH2 depletes LMP1-induced activated regulatory T cells enhancing antitumor immunity in nasopharyngeal carcinoma 否 Nasopharyngeal carcinoma nasopharyngeal carcinoma cell E_02_0349 Flow cytometry，Immunohistochemical and immunofluorescent analysis LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. Immunohistochemical staining LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. Flow cytometry，Immunohistochemical and immunofluorescent analysis EZH2 LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. 32502841 chr7 55015920 55017920 EGFR Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. human High+Lowthroughput Regorafenib suppresses epidermal growth factor receptor signaling-modulated progression of colorectal cancer 否 Colorectal cancer CT26 cell E_02_0350 Western blotting， Immunohistochemistry Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Immunohistochemical staining Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Western blotting， Immunohistochemistry EGFR Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. 32555380 chr11 44561492 44563492 CD82 Our results illustrate that, by hijacking Lef1 and CD82, vIRF1 upregulates CDCP1 to promote angiogenesis and cell invasion. human Epithelial High+Lowthroughput An oncogenic viral interferon regulatory factor upregulates CUB domain-containing protein 1 to promote angiogenesis by hijacking transcription factor lymphoid enhancer-binding factor 1 and metastasis suppressor CD82 否 Kaposi s sarcoma HUVECs E_02_0351 Immunohistochemistry (IHC) staining，RT-qPCR，western blotting，Luciferase reporter assay，Immunofluorescence assay (IFA)，DNA ChIP assay Our results illustrate that, by hijacking Lef1 and CD82, vIRF1 upregulates CDCP1 to promote angiogenesis and cell invasion. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results illustrate that, by hijacking Lef1 and CD82, vIRF1 upregulates CDCP1 to promote angiogenesis and cell invasion. Immunohistochemical staining Our results illustrate that, by hijacking Lef1 and CD82, vIRF1 upregulates CDCP1 to promote angiogenesis and cell invasion. Immunohistochemistry (IHC) staining，RT-qPCR，western blotting，Luciferase reporter assay，Immunofluorescence assay (IFA)，DNA ChIP assay CD82 Our results illustrate that, by hijacking Lef1 and CD82, vIRF1 upregulates CDCP1 to promote angiogenesis and cell invasion. 32380038 chr14 60641121 60643121 SIX1 Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis. human Epithelial High+Lowthroughput FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling 否 Cardiac hypertrophy endothelial cell E_02_0352 qRT-PCR，Western blot Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis. Immunohistochemical staining Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis. qRT-PCR，Western blot SIX1 Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis. 32407713 chr1 156460830 156462830 MEF2D Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. human Nervous High+Lowthroughput MEF2D upregulation protects neurons from oxygen-glucose deprivation/re-oxygenation-induced injury by enhancing Nrf2 activation 否 Cerebral ischemia HT22 neuronal cell E_02_0353 siRNA，RT-qPCR，Western blot，Luciferase reporter assay Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. Immunohistochemical staining Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. siRNA，RT-qPCR，Western blot，Luciferase reporter assay MEF2D Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. 32324256 chr6 45325492 45327492 RUNX2 RUNX2 and EGR1 co repressed Htra1 and increased the expression levels of other osteoblast marker genes, such as osterix, osteocalcin, and osteoprotegerin at the messenger RNA and protein level. human High+Lowthroughput RUNX2 co-operates with EGR1 to regulate osteogenic differentiation through Htra1 enhancers 否 Osteogenic differentiation preosteoblast E_02_0354 ChIP and Re‐ChIP assays，RNA extraction，quantitative reverse transcription PCR，RNA extraction，quantitative reverse transcription PCR RUNX2 and EGR1 co repressed Htra1 and increased the expression levels of other osteoblast marker genes, such as osterix, osteocalcin, and osteoprotegerin at the messenger RNA and protein level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RUNX2 and EGR1 co repressed Htra1 and increased the expression levels of other osteoblast marker genes, such as osterix, osteocalcin, and osteoprotegerin at the messenger RNA and protein level. Immunohistochemical staining RUNX2 and EGR1 co repressed Htra1 and increased the expression levels of other osteoblast marker genes, such as osterix, osteocalcin, and osteoprotegerin at the messenger RNA and protein level. ChIP and Re‐ChIP assays，RNA extraction，quantitative reverse transcription PCR，RNA extraction，quantitative reverse transcription PCR RUNX2,EGR1 RUNX2 and EGR1 co repressed Htra1 and increased the expression levels of other osteoblast marker genes, such as osterix, osteocalcin, and osteoprotegerin at the messenger RNA and protein level.;RUNX2 and EGR1 co repressed Htra1 and increased the expression levels of other osteoblast marker genes, such as osterix, osteocalcin, and osteoprotegerin at the messenger RNA and protein level. 32378708 chr11 27651837 27653837 BDNF Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. human Nervous High+Lowthroughput Brain-derived neurotrophic factor (BDNF) expression and function in the mammalian reproductive Tract 否 Endometriosis hippocampal neuron E_02_0355 RT-PCR Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. Immunohistochemical staining Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. RT-PCR BDNF Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. 32450132 chr17 27054366 27056366 Nkx2-5 We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. mouse High+Lowthroughput Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf 否 precursor cell E_02_0356 ChIP We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. Immunohistochemical staining We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. ChIP Nkx2-5 We have now found evidence for another aspect of cardiac transcription factor cooperativity between Nkx2-5 and the cardiac enriched MADS domain transcription factor Srf. 32432967 chr10 94935572 94937572 CYP2C9 There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition, and CYP2C9/CYP2C11 expression to boost the oral exposure of diclofenac. 5. human High+Lowthroughput Effect of rutin on pharmacokinetic modulation of diclofenac in rats 否 Inflammatory E_02_0357 qRT PCR There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition, and CYP2C9/CYP2C11 expression to boost the oral exposure of diclofenac. 5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition, and CYP2C9/CYP2C11 expression to boost the oral exposure of diclofenac. 5. Immunohistochemical staining There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition, and CYP2C9/CYP2C11 expression to boost the oral exposure of diclofenac. 5. qRT PCR CYP2C9 There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition, and CYP2C9/CYP2C11 expression to boost the oral exposure of diclofenac. 5. 32544883 chr5 51380949 51382949 ISL1 Modulated expression of neurotrophic factors in sciatic nerves in rats with DM developed by intraperitoneal injection of 0.45% streptozotocin, suggesting that ISL1 could delay DM progression and promote neural regeneration and repair after sciatic nerve damage. human connective High+Lowthroughput microRNA-9 and -29a regulate the progression of diabetic peripheral neuropathy via ISL1-mediated sonic hedgehog signaling pathway 否 Diabetic Peripheral Embryonic kidney cells E_02_0358 Dual luciferase reporter gene assay，RT-qPCR，Western blot，Immunohistochemistry Modulated expression of neurotrophic factors in sciatic nerves in rats with DM developed by intraperitoneal injection of 0.45% streptozotocin, suggesting that ISL1 could delay DM progression and promote neural regeneration and repair after sciatic nerve damage. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Modulated expression of neurotrophic factors in sciatic nerves in rats with DM developed by intraperitoneal injection of 0.45% streptozotocin, suggesting that ISL1 could delay DM progression and promote neural regeneration and repair after sciatic nerve damage. Immunohistochemical staining Modulated expression of neurotrophic factors in sciatic nerves in rats with DM developed by intraperitoneal injection of 0.45% streptozotocin, suggesting that ISL1 could delay DM progression and promote neural regeneration and repair after sciatic nerve damage. Dual luciferase reporter gene assay，RT-qPCR，Western blot，Immunohistochemistry ISL1 Modulated expression of neurotrophic factors in sciatic nerves in rats with DM developed by intraperitoneal injection of 0.45% streptozotocin, suggesting that ISL1 could delay DM progression and promote neural regeneration and repair after sciatic nerve damage. 32229665 chr18 69473339 69475339 Tcf4 Results: Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, β-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3β) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. mouse High+Lowthroughput Protective effect of Matricaria chamomilla extract against 1,2-dimethylhydrazine-induced colorectal cancer in mice 否 Colorectal cancer goblet cell E_02_0359 Molecular assays，RT-PCR Results: Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, β-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3β) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results: Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, β-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3β) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. Immunohistochemical staining Results: Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, β-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3β) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. Molecular assays，RT-PCR Tcf4 Results: Chamomile extract modulated the Wnt pathway in colonic tissues, where it significantly downregulated Wnt5a, β-catenin, T cell factor (Tcf4), lymphoid enhancer factor 1 (Lef1), c-Myc and Cyclin D1 expression levels, while it upregulated adenomatous polyposis coli (APC) and glycogen synthase kinase (GSK3β) expression levels. This extract significantly reduced COX-2 levels and iNOS activities. 32241803 chr10 23189894 23191894 PTF1A We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits. human Nervous High+Lowthroughput Positive autofeedback regulation of Ptf1a transcription generates the levels of PTF1A required to generate itch circuit neurons 否 Astrocyte E_02_0360 Tissue preparation, immunohistochemistry, in situ hybridization,RT-qPCR，RNA-seq We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits. Immunohistochemical staining We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits. Tissue preparation, immunohistochemistry, in situ hybridization,RT-qPCR，RNA-seq PTF1A We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits. 32303558 chr3 180986412 180988412 SOX2-OT SOX2-OT has been shown to repress the expression of SOX2, which plays roles in development, in maintaining pluripotent stem cell populations, and in neural differentiation in the cortex especially impacting GABAergic neurons (Ferri et al. 2004; Cavallaro et al. 2008; Zhang and Cui 2014; Shahryari et al. 2015; Knauss et al. human High+Lowthroughput Leveraging mouse chromatin data for heritability enrichment informs common disease architecture and reveals cortical layer contributions to schizophrenia 是 rs1805203,rs1805645 Schizophrenia E_02_0361 ATAC-seq SOX2-OT has been shown to repress the expression of SOX2, which plays roles in development, in maintaining pluripotent stem cell populations, and in neural differentiation in the cortex especially impacting GABAergic neurons (Ferri et al. 2004; Cavallaro et al. 2008; Zhang and Cui 2014; Shahryari et al. 2015; Knauss et al. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SOX2-OT has been shown to repress the expression of SOX2, which plays roles in development, in maintaining pluripotent stem cell populations, and in neural differentiation in the cortex especially impacting GABAergic neurons (Ferri et al. 2004; Cavallaro et al. 2008; Zhang and Cui 2014; Shahryari et al. 2015; Knauss et al. Immunohistochemical staining SOX2-OT has been shown to repress the expression of SOX2, which plays roles in development, in maintaining pluripotent stem cell populations, and in neural differentiation in the cortex especially impacting GABAergic neurons (Ferri et al. 2004; Cavallaro et al. 2008; Zhang and Cui 2014; Shahryari et al. 2015; Knauss et al. ATAC-seq SOX2-OT SOX2-OT has been shown to repress the expression of SOX2, which plays roles in development, in maintaining pluripotent stem cell populations, and in neural differentiation in the cortex especially impacting GABAergic neurons (Ferri et al. 2004; Cavallaro et al. 2008; Zhang and Cui 2014; Shahryari et al. 2015; Knauss et al. 32310225 chr12 3474448 3476448 Asxl2 Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. mouse bone marrow High+Lowthroughput Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure 否 Obesity bone marrow cell E_02_0362 RNA extraction，siRNA，flow cytometry，Immunohistochemical staining，Western blot，RNA-seqqPCR Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Immunohistochemical staining Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. RNA extraction，siRNA，flow cytometry，Immunohistochemical staining，Western blot，RNA-seqqPCR Asxl2 Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. 32370249 chr7 148804496 148806496 EZH2 H3K27 trimethylation (H3K27me3) by EZH2 is a key mechanism responsible for gene repression. human lymphoid High+Lowthroughput The Role of the Histone Methyltransferase EZH2 in Liver Inflammation and Fibrosis in STAM NASH Mice 否 Liver Inflammation and Fibrosis B cell E_02_0363 Real-Time Polymerase Chain Reaction H3K27 trimethylation (H3K27me3) by EZH2 is a key mechanism responsible for gene repression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq H3K27 trimethylation (H3K27me3) by EZH2 is a key mechanism responsible for gene repression. Immunohistochemical staining H3K27 trimethylation (H3K27me3) by EZH2 is a key mechanism responsible for gene repression. Real-Time Polymerase Chain Reaction EZH2 H3K27 trimethylation (H3K27me3) by EZH2 is a key mechanism responsible for gene repression. 32442533 chr10 68557663 68559663 TET1 We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. human Nervous High+Lowthroughput TET1 and 5-Hydroxymethylation Preserve the Stem Cell State of Mouse Trophoblast 否 stem cell E_02_0364 meDIP-qPCR We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. Immunohistochemical staining We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. meDIP-qPCR TET1 We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. 32443487 chr7 34815535 34817535 Cebpa Adipogenesis is induced by the increased expression of adipogenesis-inducing genes such as Cebpa, Fabp4, Pparg and Srebp1. mouse Nervous High+Lowthroughput Antiadipogenic Effects of Mixtures of Cornus officinalis and Ribes fasciculatum Extracts on 3T3-L1 Preadipocytes and High-Fat Diet-Induced Mice 否 Obesity 3T3-L1 cell E_02_0365 Quantitative Reverse-Transcription Polymerase Chain Reaction Adipogenesis is induced by the increased expression of adipogenesis-inducing genes such as Cebpa, Fabp4, Pparg and Srebp1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Adipogenesis is induced by the increased expression of adipogenesis-inducing genes such as Cebpa, Fabp4, Pparg and Srebp1. Immunohistochemical staining Adipogenesis is induced by the increased expression of adipogenesis-inducing genes such as Cebpa, Fabp4, Pparg and Srebp1. Quantitative Reverse-Transcription Polymerase Chain Reaction Cebpa,Fabp4 Adipogenesis is induced by the increased expression of adipogenesis-inducing genes such as Cebpa, Fabp4, Pparg and Srebp1.;Adipogenesis is induced by the increased expression of adipogenesis-inducing genes such as Cebpa, Fabp4, Pparg and Srebp1. 32447612 chr17 42310817 42312817 STAT3 To gain an understanding of the efects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. human Nervous High+Lowthroughput Alcohol alters IL-6 Signal Transduction in the CNS of Transgenic Mice with Increased Astrocyte Expression of IL-6 否 CNS disorders Astrocyte E_02_0366 PCR To gain an understanding of the efects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To gain an understanding of the efects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. Immunohistochemical staining To gain an understanding of the efects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. PCR STAT3 To gain an understanding of the efects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. 32499679 chr13 83649540 83651540 Mef2c We proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. mouse Nervous High+Lowthroughput Downregulation of lncRNA-11496 in the Brain Contributes to Microglia Apoptosis via Regulation of Mef2c in Chronic T. gondii Infection Mice 否 Toxoplasma gondii microglial cell E_02_0367 qRT-PCR,Western Blot,Immunohistochemistry andImmunofluorescence Assays We proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. Immunohistochemical staining We proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. qRT-PCR,Western Blot,Immunohistochemistry andImmunofluorescence Assays Mef2c We proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. 32554463 chr3 8725839 8727839 Hey1 Unlike Ezh2 loss-of-function, dual inactivation of Ezh1 and Ezh2 triggered overexpression of the transcriptional repressor Hesrelated family BHLH transcription factor with YRPW motif 1 (Hey1), downregulation of Six2, and unscheduled activation of Wnt4-driven differentiation, resulting in early termination of nephrogenesis and severe renal dysgenesis. mouse connective High+Lowthroughput The polycomb proteins EZH1 and EZH2 co-regulate chromatin accessibility and nephron progenitor cell lifespan in mice 否 Nasopharynx cancer nephron progenitor cell E_02_0368 immunohistochemistry，Section in situ hybridization，ATAC-seq，RNA-seq， Unlike Ezh2 loss-of-function, dual inactivation of Ezh1 and Ezh2 triggered overexpression of the transcriptional repressor Hesrelated family BHLH transcription factor with YRPW motif 1 (Hey1), downregulation of Six2, and unscheduled activation of Wnt4-driven differentiation, resulting in early termination of nephrogenesis and severe renal dysgenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Unlike Ezh2 loss-of-function, dual inactivation of Ezh1 and Ezh2 triggered overexpression of the transcriptional repressor Hesrelated family BHLH transcription factor with YRPW motif 1 (Hey1), downregulation of Six2, and unscheduled activation of Wnt4-driven differentiation, resulting in early termination of nephrogenesis and severe renal dysgenesis. Immunohistochemical staining Unlike Ezh2 loss-of-function, dual inactivation of Ezh1 and Ezh2 triggered overexpression of the transcriptional repressor Hesrelated family BHLH transcription factor with YRPW motif 1 (Hey1), downregulation of Six2, and unscheduled activation of Wnt4-driven differentiation, resulting in early termination of nephrogenesis and severe renal dysgenesis. immunohistochemistry，Section in situ hybridization，ATAC-seq，RNA-seq， Hey1 Unlike Ezh2 loss-of-function, dual inactivation of Ezh1 and Ezh2 triggered overexpression of the transcriptional repressor Hesrelated family BHLH transcription factor with YRPW motif 1 (Hey1), downregulation of Six2, and unscheduled activation of Wnt4-driven differentiation, resulting in early termination of nephrogenesis and severe renal dysgenesis. 32561533 chr7 55016526 55018526 EGFR Endocan facilitated EGFR signaling via direct 12 binding and enhancing of the EGF-EGFR interaction and supported the growth of 13 tumors driven by mutated EGFR. human High+Lowthroughput Circulating Proteoglycan Endocan Mediates EGFR-Driven Progression of Non-Small Cell Lung Cancer 否 Lung cancer NCI-H1975 E_02_0369 qPCR，Immunoprecipitation，Western blotting， immunohistochemical，Flow cytometry Endocan facilitated EGFR signaling via direct 12 binding and enhancing of the EGF-EGFR interaction and supported the growth of 13 tumors driven by mutated EGFR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Endocan facilitated EGFR signaling via direct 12 binding and enhancing of the EGF-EGFR interaction and supported the growth of 13 tumors driven by mutated EGFR. Immunohistochemical staining Endocan facilitated EGFR signaling via direct 12 binding and enhancing of the EGF-EGFR interaction and supported the growth of 13 tumors driven by mutated EGFR. qPCR，Immunoprecipitation，Western blotting， immunohistochemical，Flow cytometry EGFR Endocan facilitated EGFR signaling via direct 12 binding and enhancing of the EGF-EGFR interaction and supported the growth of 13 tumors driven by mutated EGFR. 32615080 chr12 102393416 102395416 IGF1 Azithromycin disturbed hepatocyte differentiation, maturation and metabolic function via upregulating GR-C/EBPα signal and reducing the expression and secretion levels of IGF1 in HepG2 cells. human High+Lowthroughput GR-C/EBPα-IGF1 axis mediated azithromycin-induced liver developmental toxicity in fetal mice 否 Perinatal mycoplasma infection HepG2 cell E_02_0370 Immunostaining，RT-qPCR，Western blotting Azithromycin disturbed hepatocyte differentiation, maturation and metabolic function via upregulating GR-C/EBPα signal and reducing the expression and secretion levels of IGF1 in HepG2 cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Azithromycin disturbed hepatocyte differentiation, maturation and metabolic function via upregulating GR-C/EBPα signal and reducing the expression and secretion levels of IGF1 in HepG2 cells. Immunohistochemical staining Azithromycin disturbed hepatocyte differentiation, maturation and metabolic function via upregulating GR-C/EBPα signal and reducing the expression and secretion levels of IGF1 in HepG2 cells. Immunostaining，RT-qPCR，Western blotting IGF1 Azithromycin disturbed hepatocyte differentiation, maturation and metabolic function via upregulating GR-C/EBPα signal and reducing the expression and secretion levels of IGF1 in HepG2 cells. 32622945 chr5 36149227 36151227 SKP2 Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. human High+Lowthroughput E3 ligase SCF(SKP2) ubiquitinates and degrades tumor suppressor C/EBPα in acute myeloid leukemia 否 Acute Myeloid Leukemia HL-60 E_02_0371 Western blot，Co-immunoprecipitation，Immunophenotyping analysis，flow cytometer，Quantitative real-time PCR Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. Immunohistochemical staining Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. Western blot，Co-immunoprecipitation，Immunophenotyping analysis，flow cytometer，Quantitative real-time PCR SKP2 Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. 32622946 chr5 36149144 36151144 SKP2 Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. human High+Lowthroughput E3 ligase SCF(SKP3) ubiquitinates and degrades tumor suppressor C/EBPα in acute myeloid leukemia 否 Acute Myeloid Leukemia U937 E_02_0372 Western blot，Co-immunoprecipitation，Immunophenotyping analysis，flow cytometer，Quantitative real-time PCR Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. Immunohistochemical staining Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. Western blot，Co-immunoprecipitation，Immunophenotyping analysis，flow cytometer，Quantitative real-time PCR SKP2 Using Estradiol-inducible K562-C/EBPα-ER cells as yet another model of granulocytic differentiation, we further confirmed that SKP2 overexpression indeed inhibits granulocytic differentiation by mitigating C/EBPα stability. 32298702 chr7 148804089 148806089 EZH2 In addition, a significant increase in the pro-inflammatory cytokine (IL-1β and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1β administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. human Nervous High+Lowthroughput Inhibition of EZH2 attenuates inhibitory synaptic transmission via the pro-inflammatory pathway in rats 否 Febrile seizures E_02_0373 Enzyme-linked immunosorbent assay，Western blot，qRT-PCR In addition, a significant increase in the pro-inflammatory cytokine (IL-1β and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1β administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In addition, a significant increase in the pro-inflammatory cytokine (IL-1β and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1β administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. Immunohistochemical staining In addition, a significant increase in the pro-inflammatory cytokine (IL-1β and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1β administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. Enzyme-linked immunosorbent assay，Western blot，qRT-PCR EZH2 In addition, a significant increase in the pro-inflammatory cytokine (IL-1β and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1β administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. 32302712 chr11 6414970 6416970 Purb On the one hand, Lnc19959.2 up-regulate ApoA4 expression via ubiquitinated transcription inhibitor factor Purb; on the other hand, lnc19959.2-hnRNPA2B1 complex acts on Cpt1a, Tm7sf2 and Gpam in some ways to reduce the efficiency of RNA polymerase II occupy on the target gene promoter. mouse High+Lowthroughput The novel long noncoding RNA Lnc19959.2 modulates triglyceride metabolism-associated genes through the interaction with Purb and hnRNPA2B1 否 Hypertriglyceridemia Brl-3a E_02_0374 RNA extraction and Transcriptome sequencing，Quantitative real-time PCR，RACE，RNA immunoprecipitation，Chromatin immunoprecipitation On the one hand, Lnc19959.2 up-regulate ApoA4 expression via ubiquitinated transcription inhibitor factor Purb; on the other hand, lnc19959.2-hnRNPA2B1 complex acts on Cpt1a, Tm7sf2 and Gpam in some ways to reduce the efficiency of RNA polymerase II occupy on the target gene promoter. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq On the one hand, Lnc19959.2 up-regulate ApoA4 expression via ubiquitinated transcription inhibitor factor Purb; on the other hand, lnc19959.2-hnRNPA2B1 complex acts on Cpt1a, Tm7sf2 and Gpam in some ways to reduce the efficiency of RNA polymerase II occupy on the target gene promoter. Immunohistochemical staining On the one hand, Lnc19959.2 up-regulate ApoA4 expression via ubiquitinated transcription inhibitor factor Purb; on the other hand, lnc19959.2-hnRNPA2B1 complex acts on Cpt1a, Tm7sf2 and Gpam in some ways to reduce the efficiency of RNA polymerase II occupy on the target gene promoter. RNA extraction and Transcriptome sequencing，Quantitative real-time PCR，RACE，RNA immunoprecipitation，Chromatin immunoprecipitation Purb On the one hand, Lnc19959.2 up-regulate ApoA4 expression via ubiquitinated transcription inhibitor factor Purb; on the other hand, lnc19959.2-hnRNPA2B1 complex acts on Cpt1a, Tm7sf2 and Gpam in some ways to reduce the efficiency of RNA polymerase II occupy on the target gene promoter. 32337955 chr1 247412880 247414880 NLRP3 Treatment with melodinhenine B attenuated the altered expression of NF-κB, IL-1β, NLRP3, ZO-1, and occluding proteins in the brain tissue of I/R-induced neuronal injury rats. human Nervous High+Lowthroughput Melodinhenine B attenuates NLRP3 expression in a cerebral ischemia/reperfusion-induced neuronal injury rat model 否 Neuronal injury E_02_0375 Western blotting，Immunohistochemical analysis Treatment with melodinhenine B attenuated the altered expression of NF-κB, IL-1β, NLRP3, ZO-1, and occluding proteins in the brain tissue of I/R-induced neuronal injury rats. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Treatment with melodinhenine B attenuated the altered expression of NF-κB, IL-1β, NLRP3, ZO-1, and occluding proteins in the brain tissue of I/R-induced neuronal injury rats. Immunohistochemical staining Treatment with melodinhenine B attenuated the altered expression of NF-κB, IL-1β, NLRP3, ZO-1, and occluding proteins in the brain tissue of I/R-induced neuronal injury rats. Western blotting，Immunohistochemical analysis NLRP3 Treatment with melodinhenine B attenuated the altered expression of NF-κB, IL-1β, NLRP3, ZO-1, and occluding proteins in the brain tissue of I/R-induced neuronal injury rats. 32346844 chr7 148804686 148806686 EZH2 We found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL- 1b, TNF-a, and IL-6) secretion in vivo. human lymphoid High+Lowthroughput Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats 否 Brachial Plexus Avulsion immune cell E_02_0376 Western Blot，q-RT PCR，Immunofluorescence Analysis We found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL- 1b, TNF-a, and IL-6) secretion in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL- 1b, TNF-a, and IL-6) secretion in vivo. Immunohistochemical staining We found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL- 1b, TNF-a, and IL-6) secretion in vivo. Western Blot，q-RT PCR，Immunofluorescence Analysis EZH2 We found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL- 1b, TNF-a, and IL-6) secretion in vivo. 32355753 chr1 10447362 10449362 CORT These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. human Nervous High+Lowthroughput Cardioprotection of cortistatin against isoproterenol-induced myocardial injury in rats 否 Myocardial injury dendritic cell E_02_0377 Western blotting These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. Immunohistochemical staining These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. Western blotting CORT These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. 32363643 chr2 202203540 202205540 SUMO1 A significant increase in small ubiquitin-like modifier 1 (SUMO1) and sumoylated C/ EBPα protein levels were observed in BPD rats, and the levels of the sumoylated C/EBPα were associated with the pulmonary surfactant proteins (SPs). human Epithelial High+Lowthroughput Sumoylation of CCAAT-enhancer-binding protein α inhibits lung differentiation in Bronchopulmonary Dysplasia model rats 否 Bronchopulmonary dysplasia epithelial cell E_02_0378 RT-PCR, Western blot，Co_x005f_x0002_immunoprecipitation A significant increase in small ubiquitin-like modifier 1 (SUMO1) and sumoylated C/ EBPα protein levels were observed in BPD rats, and the levels of the sumoylated C/EBPα were associated with the pulmonary surfactant proteins (SPs). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A significant increase in small ubiquitin-like modifier 1 (SUMO1) and sumoylated C/ EBPα protein levels were observed in BPD rats, and the levels of the sumoylated C/EBPα were associated with the pulmonary surfactant proteins (SPs). Immunohistochemical staining A significant increase in small ubiquitin-like modifier 1 (SUMO1) and sumoylated C/ EBPα protein levels were observed in BPD rats, and the levels of the sumoylated C/EBPα were associated with the pulmonary surfactant proteins (SPs). RT-PCR, Western blot，Co_x005f_x0002_immunoprecipitation SUMO1 A significant increase in small ubiquitin-like modifier 1 (SUMO1) and sumoylated C/ EBPα protein levels were observed in BPD rats, and the levels of the sumoylated C/EBPα were associated with the pulmonary surfactant proteins (SPs). 32602773 chr10 67881781 67883781 SIRT1 Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. human High+Lowthroughput Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex 否 Inflammation，endorsing inflammation, articular destruction peripheral blood mononuclear cell E_02_0379 RT-PCR Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. Immunohistochemical staining Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. RT-PCR SIRT1 Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. 32344637 chr4 153681236 153683236 TLR2 These mechanisms included B-cell maturation, antibody-mediated opsonization of mycobacteria, Fc-receptor (FcR)-mediated phagocytosis, macrophage response, interference with the α-Gal antagonistic effect of the toll-like receptor 2 (TLR2)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated immune response, and upregulation of pro-inflammatory cytokines. human High+Lowthroughput Vaccination with Alpha-Gal Protects Against Mycobacterial Infection in the Zebrafish Model of Tuberculosis 否 Tuberculosis B cell E_02_0380 Flow Cytometry These mechanisms included B-cell maturation, antibody-mediated opsonization of mycobacteria, Fc-receptor (FcR)-mediated phagocytosis, macrophage response, interference with the α-Gal antagonistic effect of the toll-like receptor 2 (TLR2)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated immune response, and upregulation of pro-inflammatory cytokines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These mechanisms included B-cell maturation, antibody-mediated opsonization of mycobacteria, Fc-receptor (FcR)-mediated phagocytosis, macrophage response, interference with the α-Gal antagonistic effect of the toll-like receptor 2 (TLR2)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated immune response, and upregulation of pro-inflammatory cytokines. Immunohistochemical staining These mechanisms included B-cell maturation, antibody-mediated opsonization of mycobacteria, Fc-receptor (FcR)-mediated phagocytosis, macrophage response, interference with the α-Gal antagonistic effect of the toll-like receptor 2 (TLR2)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated immune response, and upregulation of pro-inflammatory cytokines. Flow Cytometry TLR2 These mechanisms included B-cell maturation, antibody-mediated opsonization of mycobacteria, Fc-receptor (FcR)-mediated phagocytosis, macrophage response, interference with the α-Gal antagonistic effect of the toll-like receptor 2 (TLR2)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated immune response, and upregulation of pro-inflammatory cytokines. 30463291 chr8 144312388 144314388 DGAT1 The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. human white adipose High+Lowthroughput Ishige okamurae Extract Suppresses Obesity and Hepatic Steatosis in High Fat Diet-Induced Obese Mice 否 Hepatic steatosis, obesity E_02_0381 Cell Viability Assay,Western Blot Analysis,Oil Red O Staining The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. Immunohistochemical staining The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. Cell Viability Assay,Western Blot Analysis,Oil Red O Staining DGAT1,FAS,CPT2 The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver.;The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver.;The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. 30462329 chr5 143486631 143488631 Rac1 Co-treatment with Fasudil prevented axonal degeneration by mitigating neurite extension/retraction incoordination caused by methylmercury-induced suppression of Rac1 in vitro and in subacute methylmercury-intoxicated rats. mouse High+Lowthroughput Fasudil, a Rho-Associated Coiled Coil-Forming Protein Kinase Inhibitor, Recovers Methylmercury-Induced Axonal Degeneration by Changing Microglial Phenotype in Rats 否 Chronic Methyl-mercury Poisoning microglial cell E_02_0382 ROCK activity assay,Western blot Co-treatment with Fasudil prevented axonal degeneration by mitigating neurite extension/retraction incoordination caused by methylmercury-induced suppression of Rac1 in vitro and in subacute methylmercury-intoxicated rats. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Co-treatment with Fasudil prevented axonal degeneration by mitigating neurite extension/retraction incoordination caused by methylmercury-induced suppression of Rac1 in vitro and in subacute methylmercury-intoxicated rats. Immunohistochemical staining Co-treatment with Fasudil prevented axonal degeneration by mitigating neurite extension/retraction incoordination caused by methylmercury-induced suppression of Rac1 in vitro and in subacute methylmercury-intoxicated rats. ROCK activity assay,Western blot Rac1 Co-treatment with Fasudil prevented axonal degeneration by mitigating neurite extension/retraction incoordination caused by methylmercury-induced suppression of Rac1 in vitro and in subacute methylmercury-intoxicated rats. 30456456 chr8 144311977 144313977 DGAT1 Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. human High+Lowthroughput Butyric acid induces spontaneous adipocytic differentiation of porcine bone marrow-derived mesenchymal stem cells 否 Other mesenchymal stem cell E_02_0383 Proliferation study,Differentiation study,Differentiation study,Cytochemical staining Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. Immunohistochemical staining Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. Proliferation study,Differentiation study,Differentiation study,Cytochemical staining DGAT1,FAS,CPT2 Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study.;Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study.;Treatment with BA modulated the expression of adipocytic differentiation markers: peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly increased by both BA-2.5 and BA-5 throughout the study, while lipoprotein lipase and fatty acid-binding protein 4 were increased by BA-5 at day 3, and decreased by both BA-5 and BA- 2.5 later throughout the study. 30453072 chr1 78074974 78076974 Pax3 We discovered that myoblast determining factor (MyoD) binding elements play a key role and participate in the transcriptional regulation of MYHM2528 1 expression in zebrafish embryos. We further discovered that paired box protein (Pax3) are required for promoting MYHM2528 1 expression and myocyte enhancer factor- 2 (MEF2) binding sites participate in the transcriptional regulation of MYHM2528 1 expression in slow/fast skeletal muscles. Our study also confirmed that the nuclear factor of activated T-cell (NFAT) binding sites take part in the transcriptional regulation of MYHM2528 1 expression in slow and fast muscles fiber in relation to indeterminate muscle growth. mouse High+Lowthroughput Multiple transcription factors mediating the expressional regulation of myosin heavy chain gene involved in the indeterminate muscle growth of fish 否 epithelial cell E_02_0384 Immunohistochemical analysis，Real-time PCR We discovered that myoblast determining factor (MyoD) binding elements play a key role and participate in the transcriptional regulation of MYHM2528 1 expression in zebrafish embryos. We further discovered that paired box protein (Pax3) are required for promoting MYHM2528 1 expression and myocyte enhancer factor- 2 (MEF2) binding sites participate in the transcriptional regulation of MYHM2528 1 expression in slow/fast skeletal muscles. Our study also confirmed that the nuclear factor of activated T-cell (NFAT) binding sites take part in the transcriptional regulation of MYHM2528 1 expression in slow and fast muscles fiber in relation to indeterminate muscle growth. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We discovered that myoblast determining factor (MyoD) binding elements play a key role and participate in the transcriptional regulation of MYHM2528 1 expression in zebrafish embryos. We further discovered that paired box protein (Pax3) are required for promoting MYHM2528 1 expression and myocyte enhancer factor- 2 (MEF2) binding sites participate in the transcriptional regulation of MYHM2528 1 expression in slow/fast skeletal muscles. Our study also confirmed that the nuclear factor of activated T-cell (NFAT) binding sites take part in the transcriptional regulation of MYHM2528 1 expression in slow and fast muscles fiber in relation to indeterminate muscle growth. Immunohistochemical staining We discovered that myoblast determining factor (MyoD) binding elements play a key role and participate in the transcriptional regulation of MYHM2528 1 expression in zebrafish embryos. We further discovered that paired box protein (Pax3) are required for promoting MYHM2528 1 expression and myocyte enhancer factor- 2 (MEF2) binding sites participate in the transcriptional regulation of MYHM2528 1 expression in slow/fast skeletal muscles. Our study also confirmed that the nuclear factor of activated T-cell (NFAT) binding sites take part in the transcriptional regulation of MYHM2528 1 expression in slow and fast muscles fiber in relation to indeterminate muscle growth. Immunohistochemical analysis，Real-time PCR Pax3 We discovered that myoblast determining factor (MyoD) binding elements play a key role and participate in the transcriptional regulation of MYHM2528 1 expression in zebrafish embryos. We further discovered that paired box protein (Pax3) are required for promoting MYHM2528 1 expression and myocyte enhancer factor- 2 (MEF2) binding sites participate in the transcriptional regulation of MYHM2528 1 expression in slow/fast skeletal muscles. Our study also confirmed that the nuclear factor of activated T-cell (NFAT) binding sites take part in the transcriptional regulation of MYHM2528 1 expression in slow and fast muscles fiber in relation to indeterminate muscle growth. 30452487 chr7 148804413 148806413 EZH2 Enhancer of Zeste Homolog 2 (EZH2), a histone-lysine N-methyltransferase and a component of the Polycomb Repressive Complex 2, has been shown to play a role in GvHD pathology. human High+Lowthroughput Selective targeting of histone modification fails to prevent graft versus host disease after hematopoietic cell transplantation 否 Graft versus host disease T cell E_02_0385 Flow cytometric analysis，In vitro T cell activation Enhancer of Zeste Homolog 2 (EZH2), a histone-lysine N-methyltransferase and a component of the Polycomb Repressive Complex 2, has been shown to play a role in GvHD pathology. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of Zeste Homolog 2 (EZH2), a histone-lysine N-methyltransferase and a component of the Polycomb Repressive Complex 2, has been shown to play a role in GvHD pathology. Immunohistochemical staining Enhancer of Zeste Homolog 2 (EZH2), a histone-lysine N-methyltransferase and a component of the Polycomb Repressive Complex 2, has been shown to play a role in GvHD pathology. Flow cytometric analysis，In vitro T cell activation EZH2 Enhancer of Zeste Homolog 2 (EZH2), a histone-lysine N-methyltransferase and a component of the Polycomb Repressive Complex 2, has been shown to play a role in GvHD pathology. 30446251 chrX 49247427 49249427 FOXP3 The expanded human Tregs had demethylated FOXP3 and CTLA4 signatures and were immunosuppressive. These results describe a next-generation immunotherapy using a long-lived and Treg-selective IL-2 that activates and expands functional Tregs in vivo. human High+Lowthroughput A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease 否 Autoimmune diseases T cell E_02_0386 Surface plasmon resonance,DNA demethylation of FOXP3 and CTLA4, The expanded human Tregs had demethylated FOXP3 and CTLA4 signatures and were immunosuppressive. These results describe a next-generation immunotherapy using a long-lived and Treg-selective IL-2 that activates and expands functional Tregs in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expanded human Tregs had demethylated FOXP3 and CTLA4 signatures and were immunosuppressive. These results describe a next-generation immunotherapy using a long-lived and Treg-selective IL-2 that activates and expands functional Tregs in vivo. Immunohistochemical staining The expanded human Tregs had demethylated FOXP3 and CTLA4 signatures and were immunosuppressive. These results describe a next-generation immunotherapy using a long-lived and Treg-selective IL-2 that activates and expands functional Tregs in vivo. Surface plasmon resonance,DNA demethylation of FOXP3 and CTLA4, FOXP3 The expanded human Tregs had demethylated FOXP3 and CTLA4 signatures and were immunosuppressive. These results describe a next-generation immunotherapy using a long-lived and Treg-selective IL-2 that activates and expands functional Tregs in vivo. 30445632 chr9 2618555 2620555 VLDLR An enhancer of VLDLR expression and suggest that altered binding of one or more factors bound to rs3780181 alleles decreases enhancer activity and reduces at least VLDLR expression, leading to increased TC and LDL-C. human High+Lowthroughput Enhancer deletion and allelic effects define a regulatory molecular mechanism at the VLDLR cholesterol GWAS locus 是 rs3780181 Cardiovascular disease E_02_0387 Transcriptional reporter and EMSAs， DNA affinity pull-down assay，dual-luciferase reporter assay，DNA-affinity capture assay， tandem mass spectrometry analysis An enhancer of VLDLR expression and suggest that altered binding of one or more factors bound to rs3780181 alleles decreases enhancer activity and reduces at least VLDLR expression, leading to increased TC and LDL-C. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq An enhancer of VLDLR expression and suggest that altered binding of one or more factors bound to rs3780181 alleles decreases enhancer activity and reduces at least VLDLR expression, leading to increased TC and LDL-C. Immunohistochemical staining An enhancer of VLDLR expression and suggest that altered binding of one or more factors bound to rs3780181 alleles decreases enhancer activity and reduces at least VLDLR expression, leading to increased TC and LDL-C. Transcriptional reporter and EMSAs， DNA affinity pull-down assay，dual-luciferase reporter assay，DNA-affinity capture assay， tandem mass spectrometry analysis VLDLR An enhancer of VLDLR expression and suggest that altered binding of one or more factors bound to rs3780181 alleles decreases enhancer activity and reduces at least VLDLR expression, leading to increased TC and LDL-C. 30445463 chr5 88714221 88716221 MEF2C Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, that do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. human High+Lowthroughput A neuronal enhancer network upstream of MEF2C is compromised in patients with Rett-like characteristics 否 Neurodevelopmental disorders (e.g., Rett like syndrome) Radial glial cell E_02_0388 4Cseq,ATAC-se,RNA isolation, cDNA synthesis,quantitative PCR,4C peak conservation,4C peak ZipperPlot analyses,Luciferase enhancer assays,ATAC-seq Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, that do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, that do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. Immunohistochemical staining Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, that do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. 4Cseq,ATAC-se,RNA isolation, cDNA synthesis,quantitative PCR,4C peak conservation,4C peak ZipperPlot analyses,Luciferase enhancer assays,ATAC-seq MEF2C Mutations in myocyte enhancer factor 2C (MEF2C), an important transcription factor in neurodevelopment, are associated with a Rett-like syndrome. Structural variants (SVs) upstream of MEF2C, that do not disrupt the gene itself, have also been found in patients with a similar phenotype, suggesting that disruption of MEF2C regulatory elements can also cause a Rett-like phenotype. 30442871 chr12 120299714 120301714 SIRT4 E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. human High+Lowthroughput Study of expression analysis of SIRT4 and the coordinate regulation of bovine adipocyte differentiation by SIRT4 and its transcription factors 否 Other bovine adipocytes E_02_0389 qPCR,Immunofluorescence assays,Cell isolation, culture, and transfection,Site-directed mutagenesis,Knock down,EMSAs E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. Immunohistochemical staining E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. qPCR,Immunofluorescence assays,Cell isolation, culture, and transfection,Site-directed mutagenesis,Knock down,EMSAs SIRT4,E2F1,HOXA5,IRF4,CREB1 E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. ;E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. ;E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. ;E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. ;E2F1, CEBPβ, and HOXA5 transcriptionally activate SIRT4 expression, whereas, IRF4, PAX4, and CREB1 transcriptionally repress SIRT4 expression. We further verified that SIRT4 knockdown could affect the ability of these transcription factors to regulate the differentiation of bovine adipocytes. 30427204 chr10 42055300 42057300 Foxo3 Foxo3 promotes cell proliferation and inhibits myotube differentiation in chicken myoblast cells. Therefore, the regulation of Foxo3 could be applied to improve muscle differentiation in commercial poultry. mouse High+Lowthroughput Forkhead box O3 promotes cell proliferation and inhibits myotube differentiation in chicken myoblast cells 否 Other E_02_0390 qRT-PCR，Western blot，Cell imaging，knockdown vector transfection Foxo3 promotes cell proliferation and inhibits myotube differentiation in chicken myoblast cells. Therefore, the regulation of Foxo3 could be applied to improve muscle differentiation in commercial poultry. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Foxo3 promotes cell proliferation and inhibits myotube differentiation in chicken myoblast cells. Therefore, the regulation of Foxo3 could be applied to improve muscle differentiation in commercial poultry. Immunohistochemical staining Foxo3 promotes cell proliferation and inhibits myotube differentiation in chicken myoblast cells. Therefore, the regulation of Foxo3 could be applied to improve muscle differentiation in commercial poultry. qRT-PCR，Western blot，Cell imaging，knockdown vector transfection Foxo3 Foxo3 promotes cell proliferation and inhibits myotube differentiation in chicken myoblast cells. Therefore, the regulation of Foxo3 could be applied to improve muscle differentiation in commercial poultry. 30416963 chr6 34233962 34235962 HMGA1 Entire DNA sequence upstream the transcription start sites is probably involved in vanadate-induced inhibition, the short sequence downstream of position 464 and is sufficient for inhibition. Potential targets of vanadate are the transcription factors FoxO1 and HMGA1, two downstream targets of the insulin signaling pathway which have been shown to mediate the inhibitory effect of insulin on IR gene expression. human High+Lowthroughput Vanadate inhibits transcription of the rat insulin receptor gene via a proximal sequence of the 5'flanking region 否 liver cancer Cancer cell E_02_0391 Cloning，Extraction，Sequence analysis， Entire DNA sequence upstream the transcription start sites is probably involved in vanadate-induced inhibition, the short sequence downstream of position 464 and is sufficient for inhibition. Potential targets of vanadate are the transcription factors FoxO1 and HMGA1, two downstream targets of the insulin signaling pathway which have been shown to mediate the inhibitory effect of insulin on IR gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Entire DNA sequence upstream the transcription start sites is probably involved in vanadate-induced inhibition, the short sequence downstream of position 464 and is sufficient for inhibition. Potential targets of vanadate are the transcription factors FoxO1 and HMGA1, two downstream targets of the insulin signaling pathway which have been shown to mediate the inhibitory effect of insulin on IR gene expression. Immunohistochemical staining Entire DNA sequence upstream the transcription start sites is probably involved in vanadate-induced inhibition, the short sequence downstream of position 464 and is sufficient for inhibition. Potential targets of vanadate are the transcription factors FoxO1 and HMGA1, two downstream targets of the insulin signaling pathway which have been shown to mediate the inhibitory effect of insulin on IR gene expression. Cloning，Extraction，Sequence analysis， HMGA1 Entire DNA sequence upstream the transcription start sites is probably involved in vanadate-induced inhibition, the short sequence downstream of position 464 and is sufficient for inhibition. Potential targets of vanadate are the transcription factors FoxO1 and HMGA1, two downstream targets of the insulin signaling pathway which have been shown to mediate the inhibitory effect of insulin on IR gene expression. 30416088 chr17 85795937 85796217 Gm29418 Over-expression of Gm29418 led to an increase in Six2 mRNA expression levels in a mouse MM cell line. In conclusion, we identified a lncRNA, Gm29418, in nephron progenitor cells that has an enhancer-like function on a key regulatory gene, Six2 mouse Low+High throughput Comprehensive analysis of chromatin signature and transcriptome uncovers functional lncRNAs expressed in nephron progenitor cells 否 -- nephron progenitor cell E_02_0392 ChIP-seq We conducted comprehensive analyses of the chromatin signature and transcriptome by RNA_x0002_seq and ChIP-seq.We found seventeen lncRNAs that were expressed specifically in MM cells with an active chromatin signature, while remaining silenced in a bivalent chromatin state in non-MM cells.Out of these MM specific lncRNAs, we identified a lncRNA, Gm29418, in a distal enhancer region of Six2,a key regulatory gene of MM cells. Enhancer -- ChIP-seq,RNA-seq,qRT-PCR Six2 -- -- -- -- -- -- -- Six2 -- We conducted comprehensive analyses of the chromatin signature and transcriptome by RNA_x0002_seq and ChIP-seq.We found seventeen lncRNAs that were expressed specifically in MM cells with an active chromatin signature, while remaining silenced in a bivalent chromatin state in non-MM cells.Out of these MM specific lncRNAs, we identified a lncRNA, Gm29418, in a distal enhancer region of Six2,a key regulatory gene of MM cells. -- 30414142 chr13 40553554 40555554 FOXO1 We will discuss classical and emerging technologies by which one can understand the role of binding of specific transcription factors in regulation of transcription of FOXO genes. human High+Lowthroughput Identification of Transcription Factor-Binding Sites in the Mouse FOXO1 Promoter 否 E_02_0393 We will discuss classical and emerging technologies by which one can understand the role of binding of specific transcription factors in regulation of transcription of FOXO genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We will discuss classical and emerging technologies by which one can understand the role of binding of specific transcription factors in regulation of transcription of FOXO genes. Immunohistochemical staining We will discuss classical and emerging technologies by which one can understand the role of binding of specific transcription factors in regulation of transcription of FOXO genes. FOXO1 We will discuss classical and emerging technologies by which one can understand the role of binding of specific transcription factors in regulation of transcription of FOXO genes. 30407878 chr12 55739984 55741984 GDF11 GDF11 antagonizes TNF-a–induced inflammation and protects against the development of inflammatory arthritis in mice human High+Lowthroughput GDF11 antagonizes TNF-α-induced inflammation and protects against the development of inflammatory arthritis in mice 否 Inflammatory arthritis in mice E_02_0394 GDF11 antagonizes TNF-a–induced inflammation and protects against the development of inflammatory arthritis in mice Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GDF11 antagonizes TNF-a–induced inflammation and protects against the development of inflammatory arthritis in mice Immunohistochemical staining GDF11 antagonizes TNF-a–induced inflammation and protects against the development of inflammatory arthritis in mice GDF11 GDF11 antagonizes TNF-a–induced inflammation and protects against the development of inflammatory arthritis in mice 30396177 chr5 138462782 138464782 EGR1 Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis. human High+Lowthroughput Early Growth Response 1-Dependent Downregulation of Matrix Metalloproteinase 9 and Mouse Double Minute 2 Attenuates Head and Neck Squamous Cell Carcinoma Metastasis 否 Head and neck squamous cell carcinoma Head and Neck Squamous Cell E_02_0395 TCGA RNAseq,Immunohistochemical analysis, overexpression vector transfection,Quantitative real-time PCR (qPCR),Western blot,Matrigel invasion assay,Promoter–luciferase assay,Chromatin immunoprecipitation (ChIP) analysis Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis. Immunohistochemical staining Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis. TCGA RNAseq,Immunohistochemical analysis, overexpression vector transfection,Quantitative real-time PCR (qPCR),Western blot,Matrigel invasion assay,Promoter–luciferase assay,Chromatin immunoprecipitation (ChIP) analysis EGR1 Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis. 30383452 chr16 69562149 69564149 NFAT5 Whereas originally described as a hypertonicity-responsive transcription factor, these findings identify NFAT5 as a novel molecular determinant of biomechanically induced phenotype changes of VSMCs and wall stress-induced arterial remodeling processes. human High+Lowthroughput Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow- and pressure-induced arterial remodeling in mice 否 Other E_02_0396 Viral transduction,Immunofluorescence analyses,Western blot, Whereas originally described as a hypertonicity-responsive transcription factor, these findings identify NFAT5 as a novel molecular determinant of biomechanically induced phenotype changes of VSMCs and wall stress-induced arterial remodeling processes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Whereas originally described as a hypertonicity-responsive transcription factor, these findings identify NFAT5 as a novel molecular determinant of biomechanically induced phenotype changes of VSMCs and wall stress-induced arterial remodeling processes. Immunohistochemical staining Whereas originally described as a hypertonicity-responsive transcription factor, these findings identify NFAT5 as a novel molecular determinant of biomechanically induced phenotype changes of VSMCs and wall stress-induced arterial remodeling processes. Viral transduction,Immunofluorescence analyses,Western blot, NFAT5 Whereas originally described as a hypertonicity-responsive transcription factor, these findings identify NFAT5 as a novel molecular determinant of biomechanically induced phenotype changes of VSMCs and wall stress-induced arterial remodeling processes. 30380057 chr2 19447848 19449848 Ptf1a Taken together, these data demonstrate substantial transcriptome changes in the Sd mouse, and indicate that the effect of the ERV insertion on Ptf1a expression may be mediated by increased chromatin accessibility at a conserved Ptf1a enhancer. mouse High+Lowthroughput Genome-wide chromatin accessibility and transcriptome profiling show minimal epigenome changes and coordinated transcriptional dysregulation of hedgehog signaling in Danforth's short tail mice 否 Other acinar cell E_02_0397 mRNA-seq,ATAC-seq,GO enrichment,ChIP-seq,X-gal staining, Immunofluorescence Taken together, these data demonstrate substantial transcriptome changes in the Sd mouse, and indicate that the effect of the ERV insertion on Ptf1a expression may be mediated by increased chromatin accessibility at a conserved Ptf1a enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Taken together, these data demonstrate substantial transcriptome changes in the Sd mouse, and indicate that the effect of the ERV insertion on Ptf1a expression may be mediated by increased chromatin accessibility at a conserved Ptf1a enhancer. Immunohistochemical staining Taken together, these data demonstrate substantial transcriptome changes in the Sd mouse, and indicate that the effect of the ERV insertion on Ptf1a expression may be mediated by increased chromatin accessibility at a conserved Ptf1a enhancer. mRNA-seq,ATAC-seq,GO enrichment,ChIP-seq,X-gal staining, Immunofluorescence Ptf1a Taken together, these data demonstrate substantial transcriptome changes in the Sd mouse, and indicate that the effect of the ERV insertion on Ptf1a expression may be mediated by increased chromatin accessibility at a conserved Ptf1a enhancer. 30365070 chr6 125744351 125746351 HEY2 In conclusion, the results demonstrated that miR-98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice. human hippocampal High+Lowthroughput MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice 否 Alzheimer disease Hippocampal neuron E_02_0398 Hematoxylin and eosin (H&E) staining,Immunohistochemistry,TUNEL staining,RT‑qPCR,Western blot, In conclusion, the results demonstrated that miR-98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In conclusion, the results demonstrated that miR-98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice. Immunohistochemical staining In conclusion, the results demonstrated that miR-98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice. Hematoxylin and eosin (H&E) staining,Immunohistochemistry,TUNEL staining,RT‑qPCR,Western blot, HEY2 In conclusion, the results demonstrated that miR-98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice. 30354239 chr11 108113833 108115833 ACAT1 Elimination of ACAT1 in bone marrow-derived cells aggravates cutaneous xanthoma and atherosclerosis. The development of cutaneous xanthoma is induced mainly via the NLRP3 inflammasome activation. human High+Lowthroughput Inflammasome Activation Aggravates Cutaneous Xanthomatosis and Atherosclerosis in ACAT1 (Acyl-CoA Cholesterol Acyltransferase 1) Deficiency in Bone Marrow 否 Cutaneous xanthomatosis and atherosclerosis Mouse peritoneal macrophages E_02_0399 Quantitative Real-Time Polymerase Chain Reaction,ELISA Elimination of ACAT1 in bone marrow-derived cells aggravates cutaneous xanthoma and atherosclerosis. The development of cutaneous xanthoma is induced mainly via the NLRP3 inflammasome activation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Elimination of ACAT1 in bone marrow-derived cells aggravates cutaneous xanthoma and atherosclerosis. The development of cutaneous xanthoma is induced mainly via the NLRP3 inflammasome activation. Immunohistochemical staining Elimination of ACAT1 in bone marrow-derived cells aggravates cutaneous xanthoma and atherosclerosis. The development of cutaneous xanthoma is induced mainly via the NLRP3 inflammasome activation. Quantitative Real-Time Polymerase Chain Reaction,ELISA ACAT1,NLRP3 Elimination of ACAT1 in bone marrow-derived cells aggravates cutaneous xanthoma and atherosclerosis. The development of cutaneous xanthoma is induced mainly via the NLRP3 inflammasome activation.;Elimination of ACAT1 in bone marrow-derived cells aggravates cutaneous xanthoma and atherosclerosis. The development of cutaneous xanthoma is induced mainly via the NLRP3 inflammasome activation. 30349541 chrX 7437025 7439025 Foxp3 CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-c and IL-4 on Foxp3 expression. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments. mouse High+Lowthroughput Regulation of Lymphatic GM-CSF Expression by the E3 Ubiquitin Ligase Cbl-b 否 inflammation regulatory T cell E_02_0400 Retroviral transduction,Intracellular staining,Quantitative real-time PCR,Chromatin immunoprecipitation assays,Bisulfite sequencing,Electrophoretic mobility shift assay CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-c and IL-4 on Foxp3 expression. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-c and IL-4 on Foxp3 expression. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments. Immunohistochemical staining CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-c and IL-4 on Foxp3 expression. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments. Retroviral transduction,Intracellular staining,Quantitative real-time PCR,Chromatin immunoprecipitation assays,Bisulfite sequencing,Electrophoretic mobility shift assay Foxp3 CCAAT/enhancer-binding protein (C/EBP) functions as a safeguard that enhances Treg cell generation by dampening the inhibitory effect of IFN-c and IL-4 on Foxp3 expression. These results establish C/EBP as a new molecular target for enhancing the formation and stability of Treg cells in inflammatory environments. 30349097 chr12 64449530 64451530 TBK1 Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass. human High+Lowthroughput Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic β-cells 否 diabetes Beta cell E_02_0401 Immunohistochemistry, glucose-stimulated insulin secretion (GSIS) assay Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass. Immunohistochemical staining Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass. Immunohistochemistry, glucose-stimulated insulin secretion (GSIS) assay TBK1 Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass. 30333752 chr22 29600833 29602833 NF2 Schwannomas are common, highly morbid, and medically untreatable tumors that can arise in patients with germline as well as somatic mutations in NF2. These mutations most commonly result in the loss of function of the NF2 encoded protein, Merlin. human High+Lowthroughput Trans-Chalcone Attenuates Pain and Inflammation in Experimental Acute Gout Arthritis in Mice 否 Gouty arthritis inflammatory cell E_02_0402 Fluorescence assay,RT-qPCR, Schwannomas are common, highly morbid, and medically untreatable tumors that can arise in patients with germline as well as somatic mutations in NF2. These mutations most commonly result in the loss of function of the NF2 encoded protein, Merlin. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Schwannomas are common, highly morbid, and medically untreatable tumors that can arise in patients with germline as well as somatic mutations in NF2. These mutations most commonly result in the loss of function of the NF2 encoded protein, Merlin. Immunohistochemical staining Schwannomas are common, highly morbid, and medically untreatable tumors that can arise in patients with germline as well as somatic mutations in NF2. These mutations most commonly result in the loss of function of the NF2 encoded protein, Merlin. Fluorescence assay,RT-qPCR, NF2 Schwannomas are common, highly morbid, and medically untreatable tumors that can arise in patients with germline as well as somatic mutations in NF2. These mutations most commonly result in the loss of function of the NF2 encoded protein, Merlin. 30327653 chr19 6884691 6886691 ADGRE1 ADGRE1 mRNA was expressed by macrophages in each species, with inter-species variation both in expression level and response to lipopolysaccharide (LPS) stimulation. human High+Lowthroughput ADGRE1 (EMR1, F4/80) Is a Rapidly-Evolving Gene Expressed in Mammalian Monocyte-Macrophages 否 Other Macrophage E_02_0403 ELISA，Flow Cytometry，Immunohistochemistry，RNA-Seq ADGRE1 mRNA was expressed by macrophages in each species, with inter-species variation both in expression level and response to lipopolysaccharide (LPS) stimulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ADGRE1 mRNA was expressed by macrophages in each species, with inter-species variation both in expression level and response to lipopolysaccharide (LPS) stimulation. Immunohistochemical staining ADGRE1 mRNA was expressed by macrophages in each species, with inter-species variation both in expression level and response to lipopolysaccharide (LPS) stimulation. ELISA，Flow Cytometry，Immunohistochemistry，RNA-Seq ADGRE1 ADGRE1 mRNA was expressed by macrophages in each species, with inter-species variation both in expression level and response to lipopolysaccharide (LPS) stimulation. 30327417 chr16 10440279 10442279 NFAT5 Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity human Low throughput Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5 否 -- macrophage E_02_0404 qChIP We then analyzed peak A and Ciita promoter I by qChIP in NFAT5-deficient or control macrophages for different histone modifications that are enriched in gene enhancers (H3K4me1) or promoters (H3K4me3) and a modification that marks transcribed regions and active enhancers.We observed that peak A region had a slightly higher content in H3K4me1 compared with Ciita promoter I, and this was NFAT5 independent. Enhancer -- ChIP-seq C2ta,EG669998,Gm9475,Mhc2ta -- -- -- AI225870,B130038B15Rik,CAG-8,CAG80,NFATL1,OREBP,TonEBP,mKIAA0827,nfatz qChIP -- -- Ciita Nfat5 ChIP-seq analysis of wild-type and NFAT5-deficient BMDMs showing the position of NFAT5-binding site peak A 47 kb upstream of the Ciita locus. We therefore asked whether NFAT5 bound these regulatory regions. Quantitative chromatin immunoprecipitation (qChIP) with a combination of two polyclonal antibodies to NFAT5 detected its specific binding to promoter I of Ciita and the promoter of H2-Ab both in untreated macrophages as well as in macrophages treated with IFNγ.This result indicated that NFAT5 is a relevant factor to control Ciita expression in macrophages through its myeloid promoter I. Altogether,our analysis of primary myeloid and lymphoid APCs uncovered a selective requirement of NFAT5 in macrophages for expressing CIITA and MHCII. 30325084 chr13 118803388 118805388 Fgf10 Fgf10 is expressed in various tissues and organs, such as the limb bud, heart, inner ear and head mesenchyme. Previous studies identified Fgf10 enhancers for the inner ear and heart. mouse High+Lowthroughput Characterization of cis-regulatory elements for Fgf10 expression in the chick embryo 否 Other Chick LPM cells E_02_0405 Luciferase reporter assay，Quantitative RT-PCR，RT-PCR Fgf10 is expressed in various tissues and organs, such as the limb bud, heart, inner ear and head mesenchyme. Previous studies identified Fgf10 enhancers for the inner ear and heart. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Fgf10 is expressed in various tissues and organs, such as the limb bud, heart, inner ear and head mesenchyme. Previous studies identified Fgf10 enhancers for the inner ear and heart. Immunohistochemical staining Fgf10 is expressed in various tissues and organs, such as the limb bud, heart, inner ear and head mesenchyme. Previous studies identified Fgf10 enhancers for the inner ear and heart. Luciferase reporter assay，Quantitative RT-PCR，RT-PCR Fgf10 Fgf10 is expressed in various tissues and organs, such as the limb bud, heart, inner ear and head mesenchyme. Previous studies identified Fgf10 enhancers for the inner ear and heart. 30321325 chr16 30759122 30761122 RNF40 Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity. human High+Lowthroughput Loss of RNF40 Decreases NF-κB Activity in Colorectal Cancer Cells and Reduces Colitis Burden in Mice 否 colorectal cancer Human colorectal carcinoma cell E_02_0406 siRNA transfection,Cell fractionation,Western blotting,Immunofluorescence,H&E staining and immunohistochemistry (IHC),qRT-PCR Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity. Immunohistochemical staining Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity. siRNA transfection,Cell fractionation,Western blotting,Immunofluorescence,H&E staining and immunohistochemistry (IHC),qRT-PCR RNF40 Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity. 30307955 chr1 145989806 145991806 TXNIP As indicated by our results, tranilast alleviated cGVHD-elicited inflammation and fibrosis by suppressing the expression and/or activation of TXNIP and NF-κB and preventing EMT. human High+Lowthroughput Therapeutic potential of tranilast for the treatment of chronic graft-versus-host disease in mice 否 Chronic graft versus host disease hematopoietic stem cell E_02_0407 Histological analysis and immunohistochemistry,Immunoblotting analysis,Enzyme linked immunosorbent assay (ELISA) As indicated by our results, tranilast alleviated cGVHD-elicited inflammation and fibrosis by suppressing the expression and/or activation of TXNIP and NF-κB and preventing EMT. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq As indicated by our results, tranilast alleviated cGVHD-elicited inflammation and fibrosis by suppressing the expression and/or activation of TXNIP and NF-κB and preventing EMT. Immunohistochemical staining As indicated by our results, tranilast alleviated cGVHD-elicited inflammation and fibrosis by suppressing the expression and/or activation of TXNIP and NF-κB and preventing EMT. Histological analysis and immunohistochemistry,Immunoblotting analysis,Enzyme linked immunosorbent assay (ELISA) TXNIP As indicated by our results, tranilast alleviated cGVHD-elicited inflammation and fibrosis by suppressing the expression and/or activation of TXNIP and NF-κB and preventing EMT. 30295986 chr2 9838078 9840078 Gata3 These studies identify a novel distal enhancer of Gata3 with high activity in lens and indicate that BMP and FGF signaling can up_x005f_x0002_regulate expression of Gata3 in differentiating lens fiber cells through the identified Gata3 enhancer and promoter elements. mouse Low throughput Identification of Novel Gata3 Distal Enhancers Active in Mouse Embryonic Lens 否 -- E_02_0408 Luciferase Reporter Assay,qPCR We next employed a transient transfection assay to test putative Gata3 Enhancers in Gata3-expressing 293T cells using a heterologous TATA promoter that drives Luciferasegene expression. Here we describe the identification of a novel bipartite Gata3 lens-specific Enhancer located ~18 kb upstream from its transcriptional start site. We also found that a 5 kb Gata3 promoter possesses low activity in the lens. Enhancer -- Luciferase Reporter Assay,qPCR Gata-3,jal -- -- -- -- -- -- -- Gata3 -- Here we describe the identification of a novel bipartite Gata3 lens-specific enhancer located 18 kb upstream from its transcriptional start site. We also found that a 5-kb Gata3 promoter possesses low activity in the lens. The bipartite enhancer contains arrays of AP-1, Ets-, and Smad1/5-binding sites as well as binding sites for lensassociated DNA-binding factors. -- 30285846 chr22 19327664 19329664 HIRA Together, our results provide novel insights into the mechanism by which the HIRA complex specificallyrecognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells. human High+Lowthroughput UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at cis-regulatory elements of genes in mouse ES cells 否 Other ES cell E_02_0409 Co-immunoprecipitation，GST pull-down assays，Immunofluorescence，ChIP-qPCR，ChIP-seq，RNA preparation, RT-qPCR and poly(A) RNA-seq Together, our results provide novel insights into the mechanism by which the HIRA complex specificallyrecognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Together, our results provide novel insights into the mechanism by which the HIRA complex specificallyrecognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells. Immunohistochemical staining Together, our results provide novel insights into the mechanism by which the HIRA complex specificallyrecognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells. Co-immunoprecipitation，GST pull-down assays，Immunofluorescence，ChIP-qPCR，ChIP-seq，RNA preparation, RT-qPCR and poly(A) RNA-seq HIRA Together, our results provide novel insights into the mechanism by which the HIRA complex specificallyrecognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells. 30284014 chr7 129609040 129611040 NRF1 Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when NRF1, GABPA or MEF2A were suppressed. human High+Lowthroughput Genome-wide profiling of histone H3K27 acetylation featured fatty acid signalling in pancreatic beta cells in diet-induced obesity in mice 否 Obesity and type 2 diabetes Beta cell E_02_0410 RNA-Seq，ChIP-Seq，qPCR，TSS Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when NRF1, GABPA or MEF2A were suppressed. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when NRF1, GABPA or MEF2A were suppressed. Immunohistochemical staining Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when NRF1, GABPA or MEF2A were suppressed. RNA-Seq，ChIP-Seq，qPCR，TSS NRF1 Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when NRF1, GABPA or MEF2A were suppressed. 30283453 chr21 44283260 44285260 AIRE Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC. human High+Lowthroughput Comprehensively Profiling the Chromatin Architecture of Tissue Restricted Antigen Expression in Thymic Epithelial Cells Over Development 否 Other epithelial cell of thymus E_02_0411 ChIP,Histone ChIP-Seq Analysis,ATAC-Seq,RNA-Seq Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC. Immunohistochemical staining Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC. ChIP,Histone ChIP-Seq Analysis,ATAC-Seq,RNA-Seq AIRE Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC. 30274972 chr4 105143201 105145201 TET2 Hence TET2 plays a critical role in the GC reaction and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals. human High+Lowthroughput TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis 否 B cell lymphoma B cell E_02_0412 ELISA and ELISPOT,Flow cytometry analysis,Histology and immunohistochemistry,Genomic DNA and RNA extraction,DNA seq,quantification of methylation,ChIP,Quantitative real-time PCR,hMeDIP-seq,RNA-seq Hence TET2 plays a critical role in the GC reaction and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hence TET2 plays a critical role in the GC reaction and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals. Immunohistochemical staining Hence TET2 plays a critical role in the GC reaction and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals. ELISA and ELISPOT,Flow cytometry analysis,Histology and immunohistochemistry,Genomic DNA and RNA extraction,DNA seq,quantification of methylation,ChIP,Quantitative real-time PCR,hMeDIP-seq,RNA-seq TET2 Hence TET2 plays a critical role in the GC reaction and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals. 30257211 chr16 67559479 67561479 CTCF The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x005f_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. human High+Lowthroughput Stochastic Gene Choice during Cellular Differentiation 否 Other embryonic stem cell E_02_0413 Single-Cell qRT-PCR,Chromatin Immunoprecipitation,Bisulfite Sequencing The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x005f_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x005f_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. Immunohistochemical staining The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x005f_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. Single-Cell qRT-PCR,Chromatin Immunoprecipitation,Bisulfite Sequencing CTCF The expression frequencycorrelates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in un_x005f_x0002_derstanding the interplay between cellular differenti_x0002_ation and stochastic gene choice. 30245624 chr1 231623939 231625939 DISC1 Overall, our experiments demonstrated implication of DISC1 × D2R protein-protein interactions into mechanisms of cognitive and synaptic plasticity, which help to further understand molecular-cellular mechanisms of APD of the next generation. human High+Lowthroughput Uncoupling DISC1 × D2R Protein-Protein Interactions Facilitates Latent Inhibition in Disc1-L100P Animal Model of Schizophrenia and Enhances Synaptic Plasticity via D2 Receptors 否 Schizophrenia E_02_0414 Overall, our experiments demonstrated implication of DISC1 × D2R protein-protein interactions into mechanisms of cognitive and synaptic plasticity, which help to further understand molecular-cellular mechanisms of APD of the next generation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overall, our experiments demonstrated implication of DISC1 × D2R protein-protein interactions into mechanisms of cognitive and synaptic plasticity, which help to further understand molecular-cellular mechanisms of APD of the next generation. Immunohistochemical staining Overall, our experiments demonstrated implication of DISC1 × D2R protein-protein interactions into mechanisms of cognitive and synaptic plasticity, which help to further understand molecular-cellular mechanisms of APD of the next generation. DISC1 Overall, our experiments demonstrated implication of DISC1 × D2R protein-protein interactions into mechanisms of cognitive and synaptic plasticity, which help to further understand molecular-cellular mechanisms of APD of the next generation. 30232013 chr1 107054092 107056092 PRMT6 Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects. human High+Lowthroughput Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes 否 Other NT2/D1 cell,U2OS cell,HeLa cell,HEK293T cell E_02_0415 Flow Cytometry，RNA Isolation, RT-qPCR, RNA-Seq，ChIP-qPCR， ChIP-Seq Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects. Immunohistochemical staining Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects. Flow Cytometry，RNA Isolation, RT-qPCR, RNA-Seq，ChIP-qPCR， ChIP-Seq PRMT6 Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects. 29421235 chr11 112670302 112672302 Sox9 We identified Tead, Sox9, Smad, Tcf, Meis, Rbpj, and Runx1 as the main cardiac fibroblasts TF families. Our analysis shows that in both cell types, distal enhancers, containing concentrated combinatorial clusters of multiple tissue expressed TFs recognition motifs, are combinatorically clustered around tissue specific genes. This model for tissue specific gene expression in the heart supports the general billboard model for enhancer organization. mouse High+Lowthroughput Analysis of rat cardiac myocytes and fibroblasts identifies combinatorial enhancer organization and transcription factor families 否 Other rat cardiac myocytes ，rat cardiac fibroblasts E_02_0416 Immunofluorescent analysis,ATAC-seq,RNA-seq, ChIP-seq We identified Tead, Sox9, Smad, Tcf, Meis, Rbpj, and Runx1 as the main cardiac fibroblasts TF families. Our analysis shows that in both cell types, distal enhancers, containing concentrated combinatorial clusters of multiple tissue expressed TFs recognition motifs, are combinatorically clustered around tissue specific genes. This model for tissue specific gene expression in the heart supports the general billboard model for enhancer organization. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified Tead, Sox9, Smad, Tcf, Meis, Rbpj, and Runx1 as the main cardiac fibroblasts TF families. Our analysis shows that in both cell types, distal enhancers, containing concentrated combinatorial clusters of multiple tissue expressed TFs recognition motifs, are combinatorically clustered around tissue specific genes. This model for tissue specific gene expression in the heart supports the general billboard model for enhancer organization. Immunohistochemical staining We identified Tead, Sox9, Smad, Tcf, Meis, Rbpj, and Runx1 as the main cardiac fibroblasts TF families. Our analysis shows that in both cell types, distal enhancers, containing concentrated combinatorial clusters of multiple tissue expressed TFs recognition motifs, are combinatorically clustered around tissue specific genes. This model for tissue specific gene expression in the heart supports the general billboard model for enhancer organization. Immunofluorescent analysis,ATAC-seq,RNA-seq, ChIP-seq Sox9,Runx1 We identified Tead, Sox9, Smad, Tcf, Meis, Rbpj, and Runx1 as the main cardiac fibroblasts TF families. Our analysis shows that in both cell types, distal enhancers, containing concentrated combinatorial clusters of multiple tissue expressed TFs recognition motifs, are combinatorically clustered around tissue specific genes. This model for tissue specific gene expression in the heart supports the general billboard model for enhancer organization. ;We identified Tead, Sox9, Smad, Tcf, Meis, Rbpj, and Runx1 as the main cardiac fibroblasts TF families. Our analysis shows that in both cell types, distal enhancers, containing concentrated combinatorial clusters of multiple tissue expressed TFs recognition motifs, are combinatorically clustered around tissue specific genes. This model for tissue specific gene expression in the heart supports the general billboard model for enhancer organization. 29418037 chr6 31572730 31574730 TNF Expression of IL-1 and TNF , pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. human High+Lowthroughput Constitutive overexpression of periostin delays wound healing in mouse skin 否 Other mutant lymphoma cell E_02_0417 Immunohistochemistry,Quantitative RT-PCR Expression of IL-1 and TNF , pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of IL-1 and TNF , pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. Immunohistochemical staining Expression of IL-1 and TNF , pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. Immunohistochemistry,Quantitative RT-PCR TNF Expression of IL-1 and TNF , pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. 29377931 chr17 85989752 85991752 Six2 Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. mouse High+Lowthroughput Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies 否 kidney disease mammalian nephron progenitors E_02_0418 ChIP-seq,4C-seq,Genomic Regions Enrichment of Annotations Tool (GREAT) analysis,Fluorescence-activated cell sorting,RNA-seq,qPCR,Electrophoretic mobility shift assay (EMSA),Immunoprecipitations,Immunoprecipitations Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. Immunohistochemical staining Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. ChIP-seq,4C-seq,Genomic Regions Enrichment of Annotations Tool (GREAT) analysis,Fluorescence-activated cell sorting,RNA-seq,qPCR,Electrophoretic mobility shift assay (EMSA),Immunoprecipitations,Immunoprecipitations Six2 Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. 30218403 chr1 247413468 247415468 NLRP3 Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. human High+Lowthroughput The Beta-Hydroxybutyrate Suppresses the Migration of Glioma Cells by Inhibition of NLRP3 Inflammasome. 否 Gliomas C6 cell E_02_0419 weston blot,GPCR,qPCR Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. Immunohistochemical staining Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. weston blot,GPCR,qPCR NLRP3,FGF2 Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. ;Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. 30217595 chr5 93580158 93582158 NR2F1 NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. human High+Lowthroughput A spontaneous mouse deletion in Mctp1 uncovers a long-range cis-regulatory region crucial for NR2F1 function during inner ear development. 否 deaf sensory hair cell E_02_0420 RNA SEQ, gene knockdown, immunofluorescence staining, RT qPCR NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. Immunohistochemical staining NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. RNA-seq,基因敲降,免疫荧光染色，RT-qPCR NR2F1 NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. 30216693 chr2 132414057 132416057 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). human adipose High+Lowthroughput Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment. 否 Duchenne muscular dystrophy (DMD) satellite cell E_02_0421 Real ‐ time PCR, Weston blot, immunofluorescence staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). Immunohistochemical staining Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). real‐time PCR,weston blot,免疫荧光染色 GPR39 Methods and results Using a multidisciplinary approach, we characterized the ageing related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4 , 8 , and 18 week old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8 week old mdx mice (n = 5/group). 30214582 chr6 31572964 31574964 TNF The activation of NF-κB promotes tumor necrosis factor (TNF)-α to produce VEGF and positively regulate the expression of mRNA and proteins in the VEGF pathway (21). human High+Lowthroughput Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor-κB and vascular endothelial growth factor. 否 Hepatocellular carcinoma, tumour HCC cell E_02_0422 Immunohistochemistry (IHC), Weston blot The activation of NF-κB promotes tumor necrosis factor (TNF)-α to produce VEGF and positively regulate the expression of mRNA and proteins in the VEGF pathway (21). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The activation of NF-κB promotes tumor necrosis factor (TNF)-α to produce VEGF and positively regulate the expression of mRNA and proteins in the VEGF pathway (21). Immunohistochemical staining The activation of NF-κB promotes tumor necrosis factor (TNF)-α to produce VEGF and positively regulate the expression of mRNA and proteins in the VEGF pathway (21). 免疫组化(IHC),weston blot TNF The activation of NF-κB promotes tumor necrosis factor (TNF)-α to produce VEGF and positively regulate the expression of mRNA and proteins in the VEGF pathway (21). 30209133 chr22 39516890 39518890 ATF4 We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. human High+Lowthroughput The CDK9-cyclin T1 complex mediates saturated fatty acid-induced vascular calcification by inducing expression of the transcription factor CHOP 否 Vascular calcification smooth muscle cell E_02_0423 QRT PCR, Weston blot, gene knockdown We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. Immunohistochemical staining We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. qRT-PCR,weston blot,基因敲降 ATF4,CDK9 We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. ;We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. 30208322 chr1 247413632 247415632 NLRP3 Emerging evidence suggests that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes plays a role in the pathogenesis of liver diseases (Szabo and Csak, 2012; Szabo and Petrasek, 2015). Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. human High+Lowthroughput FXR Inhibits Endoplasmic Reticulum Stress-Induced NLRP3 Inflammasome in Hepatocytes and Ameliorates Liver Injury 否 Non alcoholic fatty liver disease, inflammation, liver fibrosis hepatocyte E_02_0424 qRT-PCR,weston blot Emerging evidence suggests that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes plays a role in the pathogenesis of liver diseases (Szabo and Csak, 2012; Szabo and Petrasek, 2015). Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Emerging evidence suggests that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes plays a role in the pathogenesis of liver diseases (Szabo and Csak, 2012; Szabo and Petrasek, 2015). Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. Immunohistochemical staining Emerging evidence suggests that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes plays a role in the pathogenesis of liver diseases (Szabo and Csak, 2012; Szabo and Petrasek, 2015). Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. qRT-PCR,weston blot NLRP3,TXNIP Emerging evidence suggests that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes plays a role in the pathogenesis of liver diseases (Szabo and Csak, 2012; Szabo and Petrasek, 2015). Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. ;Emerging evidence suggests that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes plays a role in the pathogenesis of liver diseases (Szabo and Csak, 2012; Szabo and Petrasek, 2015). Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. 30206934 chr20 6765006 6767006 BMP2 Not only gene expression was affected, tension force was also able to induce ATP release, which subse- quently could promote osteogenesis by osteoblasts (Kariya et al., 2015; Sun et al., 2013). This promoting effect was proposed to be due to a stimulated expression of BMP2, 4, and 5 (Ayala Peña, Scolaro, &Santillán, 2013). human High+Lowthroughput Cyclic tensile force stimulates BMP9 synthesis and in vitro mineralization by human periodontal ligament cells 否 periodontal ligament cell E_02_0425 RT‐PCR Not only gene expression was affected, tension force was also able to induce ATP release, which subse- quently could promote osteogenesis by osteoblasts (Kariya et al., 2015; Sun et al., 2013). This promoting effect was proposed to be due to a stimulated expression of BMP2, 4, and 5 (Ayala Peña, Scolaro, &Santillán, 2013). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Not only gene expression was affected, tension force was also able to induce ATP release, which subse- quently could promote osteogenesis by osteoblasts (Kariya et al., 2015; Sun et al., 2013). This promoting effect was proposed to be due to a stimulated expression of BMP2, 4, and 5 (Ayala Peña, Scolaro, &Santillán, 2013). Immunohistochemical staining Not only gene expression was affected, tension force was also able to induce ATP release, which subse- quently could promote osteogenesis by osteoblasts (Kariya et al., 2015; Sun et al., 2013). This promoting effect was proposed to be due to a stimulated expression of BMP2, 4, and 5 (Ayala Peña, Scolaro, &Santillán, 2013). RT‐PCR BMP2 Not only gene expression was affected, tension force was also able to induce ATP release, which subse- quently could promote osteogenesis by osteoblasts (Kariya et al., 2015; Sun et al., 2013). This promoting effect was proposed to be due to a stimulated expression of BMP2, 4, and 5 (Ayala Peña, Scolaro, &Santillán, 2013). 30205834 chr14 92041650 92043650 ATXN3 Methods We first examined a role for intracellular astrocytic responses in a Drosophila model for Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease), a disease caused by expansion of the polyglutamine (polyQ) stretch in the ATXN3 gene. human High+Lowthroughput Inhibition of NF-κB in astrocytes is sufficient to delay neurodegeneration induced by proteotoxicity in neurons 否 Neurodegenerative diseases, Alzheimer's disease Astrocyte E_02_0426 RT qPCR, Weston BOT, gene knockdown Methods We first examined a role for intracellular astrocytic responses in a Drosophila model for Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease), a disease caused by expansion of the polyglutamine (polyQ) stretch in the ATXN3 gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Methods We first examined a role for intracellular astrocytic responses in a Drosophila model for Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease), a disease caused by expansion of the polyglutamine (polyQ) stretch in the ATXN3 gene. Immunohistochemical staining Methods We first examined a role for intracellular astrocytic responses in a Drosophila model for Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease), a disease caused by expansion of the polyglutamine (polyQ) stretch in the ATXN3 gene. RT-qPCR,weston bot,基因敲降 ATXN3 Methods We first examined a role for intracellular astrocytic responses in a Drosophila model for Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease), a disease caused by expansion of the polyglutamine (polyQ) stretch in the ATXN3 gene. 30203098 chr12 102392859 102394859 IGF1 In the present study, fermented corn-soybean meal significantly improved average daily gain and gain:food ratio (P < 0.05). Fermented feed (FF) significantly increased insulin-like growth factor 1 (IGF1) transcription in liver (P < 0.05). human High+Lowthroughput Fermented corn-soybean meal elevated IGF1 levels in grower-finisher pigs 否 E_02_0427 weston blot,Real-time PCR In the present study, fermented corn-soybean meal significantly improved average daily gain and gain:food ratio (P < 0.05). Fermented feed (FF) significantly increased insulin-like growth factor 1 (IGF1) transcription in liver (P < 0.05). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the present study, fermented corn-soybean meal significantly improved average daily gain and gain:food ratio (P < 0.05). Fermented feed (FF) significantly increased insulin-like growth factor 1 (IGF1) transcription in liver (P < 0.05). Immunohistochemical staining In the present study, fermented corn-soybean meal significantly improved average daily gain and gain:food ratio (P < 0.05). Fermented feed (FF) significantly increased insulin-like growth factor 1 (IGF1) transcription in liver (P < 0.05). weston blot,Real-time PCR IGF1 In the present study, fermented corn-soybean meal significantly improved average daily gain and gain:food ratio (P < 0.05). Fermented feed (FF) significantly increased insulin-like growth factor 1 (IGF1) transcription in liver (P < 0.05). 30201766 chr22 35603362 35605362 MB It was proposed that the Drosophila amnesiac gene (amn) is required for consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the fly center for olfactory learning and memory (Waddell et al., 2000). human High+Lowthroughput Amnesiac Is Required in the Adult Mushroom Body for Memory Formation 否 Amnesia E_02_0428 Immunofluorescence staining, qPCR It was proposed that the Drosophila amnesiac gene (amn) is required for consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the fly center for olfactory learning and memory (Waddell et al., 2000). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It was proposed that the Drosophila amnesiac gene (amn) is required for consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the fly center for olfactory learning and memory (Waddell et al., 2000). Immunohistochemical staining It was proposed that the Drosophila amnesiac gene (amn) is required for consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the fly center for olfactory learning and memory (Waddell et al., 2000). 免疫荧光染色, qPCR MB It was proposed that the Drosophila amnesiac gene (amn) is required for consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the fly center for olfactory learning and memory (Waddell et al., 2000). 30200840 chr2 38740810 38742810 SRSF7 Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2 within exon 6 to single nucleotide resolution and reveals that the combined activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. human High+Lowthroughput Characterization of cis-acting elements that control oscillating alternative splicing 否 N2Acell E_02_0429 RNA-Seq,RT-PCR, Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2 within exon 6 to single nucleotide resolution and reveals that the combined activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2 within exon 6 to single nucleotide resolution and reveals that the combined activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. Immunohistochemical staining Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2 within exon 6 to single nucleotide resolution and reveals that the combined activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. RNA-Seq,RT-PCR, SRSF7 Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2 within exon 6 to single nucleotide resolution and reveals that the combined activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. 30200414 chr18 55219748 55221748 TCF4 Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. human High+Lowthroughput Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells 否 Colorectal cancer, adenomatous colorectal polyposis TA cell E_02_0430 ChIP-seq,qRT-PCR,weston blot Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. Immunohistochemical staining Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. ChIP-seq,qRT-PCR,weston blot TCF4,LEF1 Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. ;Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. 30199902 chr10 88951016 88953016 FAS Lipid synthesis pro- teins such as fatty acid synthase (FAS) and sterol regulatory ele-ment-binding protein (SREBP) are involved in fatty acid and cho- lesterol synthesis, and contribute toward lipid homeostasis. human High+Lowthroughput 2,6-Dimethoxy-1,4-benzoquinone Inhibits 3T3-L1 Adipocyte Differentiation via Regulation of AMPK and mTORC1 否 Obesity E_02_0431 weston blot Lipid synthesis pro- teins such as fatty acid synthase (FAS) and sterol regulatory ele-ment-binding protein (SREBP) are involved in fatty acid and cho- lesterol synthesis, and contribute toward lipid homeostasis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lipid synthesis pro- teins such as fatty acid synthase (FAS) and sterol regulatory ele-ment-binding protein (SREBP) are involved in fatty acid and cho- lesterol synthesis, and contribute toward lipid homeostasis. Immunohistochemical staining Lipid synthesis pro- teins such as fatty acid synthase (FAS) and sterol regulatory ele-ment-binding protein (SREBP) are involved in fatty acid and cho- lesterol synthesis, and contribute toward lipid homeostasis. weston blot FAS Lipid synthesis pro- teins such as fatty acid synthase (FAS) and sterol regulatory ele-ment-binding protein (SREBP) are involved in fatty acid and cho- lesterol synthesis, and contribute toward lipid homeostasis. 30196018 chr11 27652477 27654477 BDNF Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV phosphorylation levels, thereby rescuing the decreased levels of cAMP response element- binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling in the OBX DG. human High+Lowthroughput T-type calcium channel enhancer SAK3 produces anti-depressant-like effects by promoting adult hippocampal neurogenesis in olfactory bulbectomized mice 否 depression neural progenitor cell E_02_0432 qPCR,weston blot Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV phosphorylation levels, thereby rescuing the decreased levels of cAMP response element- binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling in the OBX DG. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV phosphorylation levels, thereby rescuing the decreased levels of cAMP response element- binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling in the OBX DG. Immunohistochemical staining Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV phosphorylation levels, thereby rescuing the decreased levels of cAMP response element- binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling in the OBX DG. qPCR,weston blot BDNF Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV phosphorylation levels, thereby rescuing the decreased levels of cAMP response element- binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling in the OBX DG. 30195779 chrX 103771144 103773144 PLP1 DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20 alternative splicing away from the PLP1 form toward DM20 cause the allelic X-linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2 (SPG2), and hypomyelination of early myelinating structures (HEMS). human High+Lowthroughput Morpholino Antisense Oligomers as a Potential Therapeutic Option for the Correction of Alternative Splicing in PMD, SPG2, and HEMS 否 Spastic paraplegia Oligodendrocytes E_02_0433 RT-PCR DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20 alternative splicing away from the PLP1 form toward DM20 cause the allelic X-linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2 (SPG2), and hypomyelination of early myelinating structures (HEMS). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20 alternative splicing away from the PLP1 form toward DM20 cause the allelic X-linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2 (SPG2), and hypomyelination of early myelinating structures (HEMS). Immunohistochemical staining DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20 alternative splicing away from the PLP1 form toward DM20 cause the allelic X-linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2 (SPG2), and hypomyelination of early myelinating structures (HEMS). RT-PCR PLP1 DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20 alternative splicing away from the PLP1 form toward DM20 cause the allelic X-linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2 (SPG2), and hypomyelination of early myelinating structures (HEMS). 30195603 chr12 6531538 6533538 GAPDH Conclusions: Our findings reveal GAPDH/Siah1 signaling cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2 with the potential to treat ischemic SCI by targeting this pathway. human High+Lowthroughput Inhibiting a spinal cord signaling pathway protects against ischemia injury in rats 否 Ischemic spinal cord injury leukocyte E_02_0434 Weston blot, CO immunoprecipitation, ELISA Conclusions: Our findings reveal GAPDH/Siah1 signaling cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2 with the potential to treat ischemic SCI by targeting this pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conclusions: Our findings reveal GAPDH/Siah1 signaling cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2 with the potential to treat ischemic SCI by targeting this pathway. Immunohistochemical staining Conclusions: Our findings reveal GAPDH/Siah1 signaling cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2 with the potential to treat ischemic SCI by targeting this pathway. weston blot,共同免疫沉淀法,酶联免疫吸附法 GAPDH Conclusions: Our findings reveal GAPDH/Siah1 signaling cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2 with the potential to treat ischemic SCI by targeting this pathway. 30195387 chr8 81475654 81477654 FABP4 Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. human High+Lowthroughput Diazinon exposure activated transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) and induced adipogenesis in 3T3-L1 preadipocytes 否 Obesity 3T3‑L1 adipocytes E_02_0435 RT-PCR, immunofluorescence light staining, Western blot Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. Immunohistochemical staining Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. RT-PCR,免疫荧光光染色,Western Blot FABP4,FASN Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. ;Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. 30191953 chr3 181709352 181711352 SOX2 Overexpression of miR 302/367 cluster in MDA MB 231 and SK BR 3 breast cancer cells upregulated expression of miR 302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. human High+Lowthroughput Vitamin C counteracts miR-302/367-induced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity 否 mammary cancer breast cancer cell E_02_0436 Flow cytometry, real ‐ time PCR, Western blot Overexpression of miR 302/367 cluster in MDA MB 231 and SK BR 3 breast cancer cells upregulated expression of miR 302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overexpression of miR 302/367 cluster in MDA MB 231 and SK BR 3 breast cancer cells upregulated expression of miR 302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. Immunohistochemical staining Overexpression of miR 302/367 cluster in MDA MB 231 and SK BR 3 breast cancer cells upregulated expression of miR 302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. 流式细胞术,real‐time PCR,westoon blot SOX2 Overexpression of miR 302/367 cluster in MDA MB 231 and SK BR 3 breast cancer cells upregulated expression of miR 302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. 30187766 chr9 117701087 117703087 TLR4 Results: We identified significantly decreased STC1 expression in TLR4 knockout mouse lungs and primary lung endothelium isolated from TLR4 knockout mice. Overexpression of STC1 was associated with endothelial cytoprotection while decreased or insufficient expression was associated with increased oxidant-induced injury and death. human High+Lowthroughput Endothelial Stanniocalcin 1 Maintains Mitochondrial Bioenergetics and Prevents Oxidant-Induced Lung Injury via Toll-Like Receptor 4 否 Acute lung injury (ALI) endothelial cell E_02_0437 RT-PCR, Weston blot, immunofluorescence light staining, gene knockdown Results: We identified significantly decreased STC1 expression in TLR4 knockout mouse lungs and primary lung endothelium isolated from TLR4 knockout mice. Overexpression of STC1 was associated with endothelial cytoprotection while decreased or insufficient expression was associated with increased oxidant-induced injury and death. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Results: We identified significantly decreased STC1 expression in TLR4 knockout mouse lungs and primary lung endothelium isolated from TLR4 knockout mice. Overexpression of STC1 was associated with endothelial cytoprotection while decreased or insufficient expression was associated with increased oxidant-induced injury and death. Immunohistochemical staining Results: We identified significantly decreased STC1 expression in TLR4 knockout mouse lungs and primary lung endothelium isolated from TLR4 knockout mice. Overexpression of STC1 was associated with endothelial cytoprotection while decreased or insufficient expression was associated with increased oxidant-induced injury and death. RT-PCR,weston blot,免疫荧光光染色,基因敲降 TLR4,STC1 Results: We identified significantly decreased STC1 expression in TLR4 knockout mouse lungs and primary lung endothelium isolated from TLR4 knockout mice. Overexpression of STC1 was associated with endothelial cytoprotection while decreased or insufficient expression was associated with increased oxidant-induced injury and death.; Results: We identified significantly decreased STC1 expression in TLR4 knockout mouse lungs and primary lung endothelium isolated from TLR4 knockout mice. Overexpression of STC1 was associated with endothelial cytoprotection while decreased or insufficient expression was associated with increased oxidant-induced injury and death. 30186385 chr7 148804832 148806832 EZH2 Additionally, predictions with TargetScan software indicated that the 3 -untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. human High+Lowthroughput MicroRNA-101-3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9 否 Retinoblastoma Y79 cell E_02_0438 RT qPCR, Weston blot, MTT assay, flow cytometry, statistical analysis Additionally, predictions with TargetScan software indicated that the 3 -untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Additionally, predictions with TargetScan software indicated that the 3 -untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. Immunohistochemical staining Additionally, predictions with TargetScan software indicated that the 3 -untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. RT-qPCR,weston blot,MTT assay,流式细胞术,统计分析 EZH2,HDAC9 Additionally, predictions with TargetScan software indicated that the 3 -untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. ;Additionally, predictions with TargetScan software indicated that the 3 -untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. 30185805 chr6 124838893 124840893 Cd4 Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. mouse High+Lowthroughput Stage-specific epigenetic regulation of CD4 expression by coordinated enhancer elements during T cell development 否 T cell E_02_0439 Flow cytometry, statistical analysis, real time quantitative PCR Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. Immunohistochemical staining Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. 流式细胞术,统计分析,Real-time quantitative PCR Cd4,TET1,TET3 Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells.; Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells.; Here we show that two stage-specific Cd4 cis-elements, the pre- viously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway.Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. 30176159 chr9 36830723 36832723 PAX5 Epstein-Barr virus (EBV) expresses an abundant nuclear noncoding RNA called EBER2, which interacts with and acts as a guide RNA for the host transcription factor PAX5. human High+Lowthroughput Identification of host RNAs that interact with EBV noncoding RNA EBER2 否 E_02_0440 qRT-PCR,RNA-seq,ChIP-seq Epstein-Barr virus (EBV) expresses an abundant nuclear noncoding RNA called EBER2, which interacts with and acts as a guide RNA for the host transcription factor PAX5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Epstein-Barr virus (EBV) expresses an abundant nuclear noncoding RNA called EBER2, which interacts with and acts as a guide RNA for the host transcription factor PAX5. Immunohistochemical staining Epstein-Barr virus (EBV) expresses an abundant nuclear noncoding RNA called EBER2, which interacts with and acts as a guide RNA for the host transcription factor PAX5. qRT-PCR,RNA-seq,ChIP-seq PAX5 Epstein-Barr virus (EBV) expresses an abundant nuclear noncoding RNA called EBER2, which interacts with and acts as a guide RNA for the host transcription factor PAX5. 30173509 chr10 88950916 88952916 FAS The antibodies for phospho-AMP-activated protein kinase alpha (p-AMPKα,73 Thr 172), AMPKα, phospho-acetyl-CoA carboxylase (p-ACC, Ser 79), ACC, fatty acid74 synthase (FAS), elongation of very long-chain fatty acids protein 6 (ELOVL 6), stearoyl-CoA75 desaturase-1 (SCD1), peroxisome proliferator-activated receptor gamma (PPAR-γ),76 CCAAT/enhancer-binding protein alpha (C/EBP-α), TATA-binding protein (TBP), and β-77 actin were from Cell Signaling Technology (Danvers, MA, USA). human High+Lowthroughput Antiobesity Effect of Tricin, a Methylated Cereal Flavone, in High-Fat-Diet-Induced Obese Mice 否 Obesity, diabetes, hypertension, CVD fat cell E_02_0441 Statistical analysis, Weston blot The antibodies for phospho-AMP-activated protein kinase alpha (p-AMPKα,73 Thr 172), AMPKα, phospho-acetyl-CoA carboxylase (p-ACC, Ser 79), ACC, fatty acid74 synthase (FAS), elongation of very long-chain fatty acids protein 6 (ELOVL 6), stearoyl-CoA75 desaturase-1 (SCD1), peroxisome proliferator-activated receptor gamma (PPAR-γ),76 CCAAT/enhancer-binding protein alpha (C/EBP-α), TATA-binding protein (TBP), and β-77 actin were from Cell Signaling Technology (Danvers, MA, USA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The antibodies for phospho-AMP-activated protein kinase alpha (p-AMPKα,73 Thr 172), AMPKα, phospho-acetyl-CoA carboxylase (p-ACC, Ser 79), ACC, fatty acid74 synthase (FAS), elongation of very long-chain fatty acids protein 6 (ELOVL 6), stearoyl-CoA75 desaturase-1 (SCD1), peroxisome proliferator-activated receptor gamma (PPAR-γ),76 CCAAT/enhancer-binding protein alpha (C/EBP-α), TATA-binding protein (TBP), and β-77 actin were from Cell Signaling Technology (Danvers, MA, USA). Immunohistochemical staining The antibodies for phospho-AMP-activated protein kinase alpha (p-AMPKα,73 Thr 172), AMPKα, phospho-acetyl-CoA carboxylase (p-ACC, Ser 79), ACC, fatty acid74 synthase (FAS), elongation of very long-chain fatty acids protein 6 (ELOVL 6), stearoyl-CoA75 desaturase-1 (SCD1), peroxisome proliferator-activated receptor gamma (PPAR-γ),76 CCAAT/enhancer-binding protein alpha (C/EBP-α), TATA-binding protein (TBP), and β-77 actin were from Cell Signaling Technology (Danvers, MA, USA). 统计分析,weston blot FAS,GPAM The antibodies for phospho-AMP-activated protein kinase alpha (p-AMPKα,73 Thr 172), AMPKα, phospho-acetyl-CoA carboxylase (p-ACC, Ser 79), ACC, fatty acid74 synthase (FAS), elongation of very long-chain fatty acids protein 6 (ELOVL 6), stearoyl-CoA75 desaturase-1 (SCD1), peroxisome proliferator-activated receptor gamma (PPAR-γ),76 CCAAT/enhancer-binding protein alpha (C/EBP-α), TATA-binding protein (TBP), and β-77 actin were from Cell Signaling Technology (Danvers, MA, USA).;The antibodies for phospho-AMP-activated protein kinase alpha (p-AMPKα,73 Thr 172), AMPKα, phospho-acetyl-CoA carboxylase (p-ACC, Ser 79), ACC, fatty acid74 synthase (FAS), elongation of very long-chain fatty acids protein 6 (ELOVL 6), stearoyl-CoA75 desaturase-1 (SCD1), peroxisome proliferator-activated receptor gamma (PPAR-γ),76 CCAAT/enhancer-binding protein alpha (C/EBP-α), TATA-binding protein (TBP), and β-77 actin were from Cell Signaling Technology (Danvers, MA, USA). 30169732 chr7 16913181 16915181 AHR Using MC-deficient KitW-sh/W-sh mice and Mas-TRECK mice, which carries a diphtheria toxin (DT)-induced MC deletion system based on il4 enhancer elements, we demonstrate here that MCs are involved in the induction of house dust mite (HDM)-induced AHR. human High+Lowthroughput Allergin-1 on mast cells suppresses house dust mite-induced airway hyperresponsiveness in mice 否 asthma mast cell E_02_0442 Degranulation assay, flow cytometry, ELISA Using MC-deficient KitW-sh/W-sh mice and Mas-TRECK mice, which carries a diphtheria toxin (DT)-induced MC deletion system based on il4 enhancer elements, we demonstrate here that MCs are involved in the induction of house dust mite (HDM)-induced AHR. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using MC-deficient KitW-sh/W-sh mice and Mas-TRECK mice, which carries a diphtheria toxin (DT)-induced MC deletion system based on il4 enhancer elements, we demonstrate here that MCs are involved in the induction of house dust mite (HDM)-induced AHR. Immunohistochemical staining Using MC-deficient KitW-sh/W-sh mice and Mas-TRECK mice, which carries a diphtheria toxin (DT)-induced MC deletion system based on il4 enhancer elements, we demonstrate here that MCs are involved in the induction of house dust mite (HDM)-induced AHR. Degranulation assay,流式细胞术,ELISA法 AHR Using MC-deficient KitW-sh/W-sh mice and Mas-TRECK mice, which carries a diphtheria toxin (DT)-induced MC deletion system based on il4 enhancer elements, we demonstrate here that MCs are involved in the induction of house dust mite (HDM)-induced AHR. 30166330 chr13 83649673 83651673 Mef2c Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor. mouse High+Lowthroughput Tbx1 represses Mef2c gene expression and is correlated with histone 3 deacetylation of the anterior heart field enhancer 否 22q11.2 deletion syndrome myoblast cell E_02_0443 Immunofluorescence and alkaline phosphatase activity assay, QRT PCR, CO IP, statistical analysis Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor. Immunohistochemical staining Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor. Immunofluorescence and alkaline phosphatase activity assay,qRT-PCR,Co-IP,统计分析 Mef2c,Tbx1 Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor.;Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor. 30160785 chr6 43168442 43170442 SRF The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor-bearing mice. human High+Lowthroughput Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5 否 Colon cancer LS174T cell E_02_0444 Weston blot, immunofluorescence light staining, statistical analysis The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor-bearing mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor-bearing mice. Immunohistochemical staining The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor-bearing mice. weston blot,免疫荧光光染色,统计分析 SRF The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor-bearing mice. 30158339 chr4 70515658 70517658 AMTN AMTN-deficient mice have a hypo- mineralized inner enamel and structural defects in the outer enamel due to delayed expression of kallikrein-4 (8). During JE regeneration after gingivectomy, ODAM is first expressed at the leading edge of the wound and AMTN expression appears later, suggesting ODAM and AMTN have coordinated tasks at the cell-tooth interface (9). AMTN can promote hydroxyapatite mineralizati. human High+Lowthroughput IL-1β and TNF-α regulate mouse amelotin gene transcription in gingival epithelial cells 否 tumour ameloblast E_02_0445 Real time polymerase chain reaction (PCR), Weston blot, luciferase assays, gel shift assays, chromatin immunoprecipitation (chip) assays, statistical analysis AMTN-deficient mice have a hypo- mineralized inner enamel and structural defects in the outer enamel due to delayed expression of kallikrein-4 (8). During JE regeneration after gingivectomy, ODAM is first expressed at the leading edge of the wound and AMTN expression appears later, suggesting ODAM and AMTN have coordinated tasks at the cell-tooth interface (9). AMTN can promote hydroxyapatite mineralizati. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq AMTN-deficient mice have a hypo- mineralized inner enamel and structural defects in the outer enamel due to delayed expression of kallikrein-4 (8). During JE regeneration after gingivectomy, ODAM is first expressed at the leading edge of the wound and AMTN expression appears later, suggesting ODAM and AMTN have coordinated tasks at the cell-tooth interface (9). AMTN can promote hydroxyapatite mineralizati. Immunohistochemical staining AMTN-deficient mice have a hypo- mineralized inner enamel and structural defects in the outer enamel due to delayed expression of kallikrein-4 (8). During JE regeneration after gingivectomy, ODAM is first expressed at the leading edge of the wound and AMTN expression appears later, suggesting ODAM and AMTN have coordinated tasks at the cell-tooth interface (9). AMTN can promote hydroxyapatite mineralizati. Real-time polymerase chain reaction (PCR),weston blot,Luciferase assays,Gel shift assays,Chromatin immunoprecipitation (ChIP) assays,统计分析 AMTN AMTN-deficient mice have a hypo- mineralized inner enamel and structural defects in the outer enamel due to delayed expression of kallikrein-4 (8). During JE regeneration after gingivectomy, ODAM is first expressed at the leading edge of the wound and AMTN expression appears later, suggesting ODAM and AMTN have coordinated tasks at the cell-tooth interface (9). AMTN can promote hydroxyapatite mineralizati. 30158147 chr19 47816826 47818826 CRX Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. human High+Lowthroughput A massively parallel reporter assay reveals context-dependent activity of homeodomain binding sites in vivo 否 B cell E_02_0446 PCR,ChIP-seq,CRE-seq assay Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. Immunohistochemical staining Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. PCR,ChIP-seq,CRE-seq assay CRX,TF Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. ;Cone-rod homeobox (CRX) is a paired-like homeodomain transcription factor (TF) and a master regulator of photoreceptor development in vertebrates. 30157475 chr7 148804409 148806409 EZH2 RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. human High+Lowthroughput SNHG6 Promotes Tumor Growth via Repression of P21 in Colorectal Cancer 否 colorectal cancer Human colorectal carcinoma cell E_02_0447 Real time PCR, immunohistochemistry, Weston blot, chromatin immunoprecipitation (chip) assay, and flow cytometry RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. Immunohistochemical staining RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. real-time PCR ,免疫组化,weston blot,染色质免疫沉淀(ChIP)测定,流式细胞术 EZH2,SNHG6 RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. ;RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. 30155966 chr2 239045155 239047155 HDAC4 HDAC4 enhancer DNA methylation data were obtained from a previous MethylRAD seq. human High+Lowthroughput Correlation between HDAC4 enhancer DNA methylation and mRNA expression during palatal fusion induced by all-trans retinoic acid 是 epithelial cell E_02_0448 MS ‐ PCR, real ‐ time PCR, statistical analysis, methylrad ‐ seq HDAC4 enhancer DNA methylation data were obtained from a previous MethylRAD seq. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HDAC4 enhancer DNA methylation data were obtained from a previous MethylRAD seq. Immunohistochemical staining HDAC4 enhancer DNA methylation data were obtained from a previous MethylRAD seq. MS‐PCR,real‐time PCR,统计分析,methylRAD-seq HDAC4 HDAC4 enhancer DNA methylation data were obtained from a previous MethylRAD seq. 30154946 chr17 44900435 44902435 GFAP In the same way, we observed an increment in interleukin-1β, TNF-α, and GFAP, indicative of exacerbated inflammatory processes by the combination of MS and Aβ1 42. human High+Lowthroughput Metabolic Syndrome Exacerbates the Recognition Memory Impairment and Oxidative-Inflammatory Response in Rats with an Intrahippocampal Injection of Amyloid Beta 1-42 否 Alzheimer's disease (AD), atherosclerosis, cardiovascular disease, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), obesity microglial cell E_02_0449 Immunofluorescence staining, statistical analysis, PCR In the same way, we observed an increment in interleukin-1β, TNF-α, and GFAP, indicative of exacerbated inflammatory processes by the combination of MS and Aβ1 42. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the same way, we observed an increment in interleukin-1β, TNF-α, and GFAP, indicative of exacerbated inflammatory processes by the combination of MS and Aβ1 42. Immunohistochemical staining In the same way, we observed an increment in interleukin-1β, TNF-α, and GFAP, indicative of exacerbated inflammatory processes by the combination of MS and Aβ1 42. 免疫荧光染色,统计分析,PCR GFAP In the same way, we observed an increment in interleukin-1β, TNF-α, and GFAP, indicative of exacerbated inflammatory processes by the combination of MS and Aβ1 42. 30154726 chr10 88950948 88952948 FAS The mRNA expression of CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS), FAS activity, and the content of glycerol and triglyceride (TG) were decreased in the muscle by 509.6 and 1007.5 mg/kg VC diets. human High+Lowthroughput Investigation of the Lipid-Lowering Effect of Vitamin C Through GSK-3β/β-Catenin Signaling in Zebrafish 否 Atherosclerosis, coronary heart disease, obesity ZF4 cell E_02_0450 Real time PCR, Weston blot, statistical analysis, and immunofluorescence staining The mRNA expression of CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS), FAS activity, and the content of glycerol and triglyceride (TG) were decreased in the muscle by 509.6 and 1007.5 mg/kg VC diets. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The mRNA expression of CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS), FAS activity, and the content of glycerol and triglyceride (TG) were decreased in the muscle by 509.6 and 1007.5 mg/kg VC diets. Immunohistochemical staining The mRNA expression of CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS), FAS activity, and the content of glycerol and triglyceride (TG) were decreased in the muscle by 509.6 and 1007.5 mg/kg VC diets. real-time PCR,weston blot,统计分析,免疫荧光染色 FAS The mRNA expression of CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS), FAS activity, and the content of glycerol and triglyceride (TG) were decreased in the muscle by 509.6 and 1007.5 mg/kg VC diets. 30153568 chr5 88714138 88716138 MEF2C Furthermore, there were no statistically significant differences in cell viability, metabolic activity, population doubling time, and myocyte enhancer factor 2 (MEF2C) expression between cell cultures established from freshly harvested and one year-stored frozen tissue specimens. human High+Lowthroughput Establishment of primary myoblast cell cultures from cryopreserved skeletal muscle biopsies to serve as a tool in related research & development studies 否 Neuromuscular disorders myocyte E_02_0451 Real time RT-PCR, immunofluorescence staining, statistical analysis Furthermore, there were no statistically significant differences in cell viability, metabolic activity, population doubling time, and myocyte enhancer factor 2 (MEF2C) expression between cell cultures established from freshly harvested and one year-stored frozen tissue specimens. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, there were no statistically significant differences in cell viability, metabolic activity, population doubling time, and myocyte enhancer factor 2 (MEF2C) expression between cell cultures established from freshly harvested and one year-stored frozen tissue specimens. Immunohistochemical staining Furthermore, there were no statistically significant differences in cell viability, metabolic activity, population doubling time, and myocyte enhancer factor 2 (MEF2C) expression between cell cultures established from freshly harvested and one year-stored frozen tissue specimens. real-time RT-PCR,免疫荧光染色,统计分析 MEF2C Furthermore, there were no statistically significant differences in cell viability, metabolic activity, population doubling time, and myocyte enhancer factor 2 (MEF2C) expression between cell cultures established from freshly harvested and one year-stored frozen tissue specimens. 30151761 chr8 22111886 22113886 HR Prior to the genome editing era, the conventional knock-in strategy based on homologous recombination (HR) was the only option avail- able, but it had limitations in mouse embryonic stem cells because intrinsic HR at a target site occurs with extremely low frequency in somatic cells. human High+Lowthroughput A Simple Knock-In System for Xenopus via Microhomology Mediated End Joining Repair 否 embryonic stem cell E_02_0452 PCR, gene knockdown Prior to the genome editing era, the conventional knock-in strategy based on homologous recombination (HR) was the only option avail- able, but it had limitations in mouse embryonic stem cells because intrinsic HR at a target site occurs with extremely low frequency in somatic cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Prior to the genome editing era, the conventional knock-in strategy based on homologous recombination (HR) was the only option avail- able, but it had limitations in mouse embryonic stem cells because intrinsic HR at a target site occurs with extremely low frequency in somatic cells. Immunohistochemical staining Prior to the genome editing era, the conventional knock-in strategy based on homologous recombination (HR) was the only option avail- able, but it had limitations in mouse embryonic stem cells because intrinsic HR at a target site occurs with extremely low frequency in somatic cells. PCR,基因敲降 HR Prior to the genome editing era, the conventional knock-in strategy based on homologous recombination (HR) was the only option avail- able, but it had limitations in mouse embryonic stem cells because intrinsic HR at a target site occurs with extremely low frequency in somatic cells. 30149809 chr13 63009830 63011830 Fbp1 However, functional studies of cis-regulatory elements have been restricted to a small number of sequences that were originally identified by promoter analysis of ecdysone-induced genes. For example, Hsp27, Eip28/29, Fbp1, and Sgs-4 are induced directly by ecdysone and contain an EcRE in their basal promoter region [36 38]. mouse High+Lowthroughput The genome-wide transcriptional regulatory landscape of ecdysone in the silkworm 否 embryonic cell E_02_0453 RNA-seq,ChIP-seq,PCR However, functional studies of cis-regulatory elements have been restricted to a small number of sequences that were originally identified by promoter analysis of ecdysone-induced genes. For example, Hsp27, Eip28/29, Fbp1, and Sgs-4 are induced directly by ecdysone and contain an EcRE in their basal promoter region [36 38]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, functional studies of cis-regulatory elements have been restricted to a small number of sequences that were originally identified by promoter analysis of ecdysone-induced genes. For example, Hsp27, Eip28/29, Fbp1, and Sgs-4 are induced directly by ecdysone and contain an EcRE in their basal promoter region [36 38]. Immunohistochemical staining However, functional studies of cis-regulatory elements have been restricted to a small number of sequences that were originally identified by promoter analysis of ecdysone-induced genes. For example, Hsp27, Eip28/29, Fbp1, and Sgs-4 are induced directly by ecdysone and contain an EcRE in their basal promoter region [36 38]. RNA-seq,ChIP-seq,PCR Fbp1 However, functional studies of cis-regulatory elements have been restricted to a small number of sequences that were originally identified by promoter analysis of ecdysone-induced genes. For example, Hsp27, Eip28/29, Fbp1, and Sgs-4 are induced directly by ecdysone and contain an EcRE in their basal promoter region [36 38]. 30149019 chr8 18388409 18390409 NAT2 Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p<0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p<0.001). human High+Lowthroughput Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1 是 rs1041983,rs1801280,rs1799930,rs1799929,rs1208,rs1799931 Cancer, type 2 diabetes CD3+ cell E_02_0454 Statistical analysis, PCR Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p<0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p<0.001). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p<0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p<0.001). Immunohistochemical staining Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p<0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p<0.001). 统计分析,PCR NAT2,SIRT1 Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p<0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p<0.001). ;Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p<0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p<0.001). 30148699 chr6 41733756 41735756 PGC However, the levels of other mitochon- drial transcription factors (mtTF) such as PPAR-c coactivator (PGC)-1a and mtTFA were decreased by 32% and 35%, re- spectively, relative to untreated 3T3-L1 cells, although only the latter was statistically significant (Fig. 5B D). human High+Lowthroughput Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 Cell Extracts Inhibit Adipogenesis in 3T3-L1 and HepG2 Cells 否 Obesity 3T3-L1 cell E_02_0455 PCR, statistical analysis However, the levels of other mitochon- drial transcription factors (mtTF) such as PPAR-c coactivator (PGC)-1a and mtTFA were decreased by 32% and 35%, re- spectively, relative to untreated 3T3-L1 cells, although only the latter was statistically significant (Fig. 5B D). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, the levels of other mitochon- drial transcription factors (mtTF) such as PPAR-c coactivator (PGC)-1a and mtTFA were decreased by 32% and 35%, re- spectively, relative to untreated 3T3-L1 cells, although only the latter was statistically significant (Fig. 5B D). Immunohistochemical staining However, the levels of other mitochon- drial transcription factors (mtTF) such as PPAR-c coactivator (PGC)-1a and mtTFA were decreased by 32% and 35%, re- spectively, relative to untreated 3T3-L1 cells, although only the latter was statistically significant (Fig. 5B D). PCR,统计分析 PGC However, the levels of other mitochon- drial transcription factors (mtTF) such as PPAR-c coactivator (PGC)-1a and mtTFA were decreased by 32% and 35%, re- spectively, relative to untreated 3T3-L1 cells, although only the latter was statistically significant (Fig. 5B D). 30146478 chr11 111838889 111839334 SOX9 SRY-box 9 (SOX9) is a master transcription factor that regulates cartilage development. CRISPR/dCas9-ChIP-mass spectrometry analysis further implicated STAT3 in acting at the enhancer to regulate SOX9 expression. human Low+High throughput Combinatorial CRISPR/Cas9 Approach to Elucidate a Far-Upstream Enhancer Complex for Tissue-Specific Sox9 Expression 否 -- chondroblast E_02_0456 ChIP-qPCR We next performed the ChIP-qPCR using anti-H3K4me1 and H3K27ac antibody in all five regions and found that RCSE regions were significantly enriched in both H3K4me1 and H3K27ac ChIP, suggesting the potential enhancer. Enhancer 3C PCR 2010306G03Rik,AV220920,mKIAA4243 TG mice with the Sox9 promoter and 43 RCSE region.These data suggest that the RCSE region functions as a costal- and sternum cartilage-specific Enhancer. Transgenic mice TG mice with the Sox9 promoter and 43 RCSE region.These data suggest that the RCSE region functions as a costal- and sternum cartilage-specific Enhancer. 1110034C02Rik,AW109958,Aprf Luciferase Reporter Assay,Immunostaining -- -- Sox9,Sox9,Sox9,Sox9 Stat3,Stat3,Stat3,Stat3 These data suggest that there is a long-range interaction between the Sox9 promoter and RCSE region in primary chondrocytes.;These data suggest that there is a long-range interaction between the Sox9 promoter and RCSE region in primary chondrocytes.;These data suggest that there is a long-range interaction between the Sox9 promoter and RCSE region in primary chondrocytes.;These data suggest that there is a long-range interaction between the Sox9 promoter and RCSE region in primary chondrocytes. Furthermore, transcription factors that regulate Sox9 expres sion were screened using a CRISPR/Cas9-chromatin immuno precipitation (ChIP)-mass spectrometry (MS) system targeting the RCSE region in chondrocytes; signal transducer and acti vator of transcription 3 (Stat3) was identified as a transacting fac tor for the Sox9 Enhancer.;Furthermore, transcription factors that regulate Sox9 expres sion were screened using a CRISPR/Cas9-chromatin immuno precipitation (ChIP)-mass spectrometry (MS) system targeting the RCSE region in chondrocytes; signal transducer and acti vator of transcription 3 (Stat3) was identified as a transacting fac tor for the Sox9 Enhancer.;Furthermore, transcription factors that regulate Sox9 expres sion were screened using a CRISPR/Cas9-chromatin immuno precipitation (ChIP)-mass spectrometry (MS) system targeting the RCSE region in chondrocytes; signal transducer and acti vator of transcription 3 (Stat3) was identified as a transacting fac tor for the Sox9 Enhancer.;Furthermore, transcription factors that regulate Sox9 expres sion were screened using a CRISPR/Cas9-chromatin immuno precipitation (ChIP)-mass spectrometry (MS) system targeting the RCSE region in chondrocytes; signal transducer and acti vator of transcription 3 (Stat3) was identified as a transacting fac tor for the Sox9 Enhancer. 30146411 chr16 48121715 48123715 Dppa2 Hernandez et al. identify chromatin-associated factors Dppa2 and Dppa4 as the key components mediating the reset of somatic chromatin to a pluripotent configuration. mouse High+Lowthroughput Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to Pluripotency 否 fibroblast E_02_0457 Flow cytometry, immunofluorescence light staining, PCR, RNA SEQ, chip seq Hernandez et al. identify chromatin-associated factors Dppa2 and Dppa4 as the key components mediating the reset of somatic chromatin to a pluripotent configuration. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hernandez et al. identify chromatin-associated factors Dppa2 and Dppa4 as the key components mediating the reset of somatic chromatin to a pluripotent configuration. Immunohistochemical staining Hernandez et al. identify chromatin-associated factors Dppa2 and Dppa4 as the key components mediating the reset of somatic chromatin to a pluripotent configuration. 流式细胞术,免疫荧光光染色,PCR,RNA-seq ,ChIP-Seq Dppa2,Dppa4 Hernandez et al. identify chromatin-associated factors Dppa2 and Dppa4 as the key components mediating the reset of somatic chromatin to a pluripotent configuration.;Hernandez et al. identify chromatin-associated factors Dppa2 and Dppa4 as the key components mediating the reset of somatic chromatin to a pluripotent configuration. 30146317 chr15 76897064 76899064 Mb Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). mouse High+Lowthroughput The Evf2 Ultraconserved Enhancer lncRNA Functionally and Spatially Organizes Megabase Distant Genes in the Developing Forebrain 否 E_02_0458 QRT PCR, chipseq, statistical analysis, immunofluorescence staining Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). Immunohistochemical staining Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). qRT-PCR, ChIPseq,统计分析,免疫荧光染色 Mb,Lsm8,Akr1b8,Shh Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). ;Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). ;Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). ;Gene regulation requires selective targeting of DNA regulatory enhancers over megabase (Mb) distances. Transgene expression of Evf2 activates Lsm8 (12Mb distant), but fails to repress Akr1b8, supporting trans-activation and long-range cis repression. Early studies showed regulatory interactions between the sonic hedgehog (Shh) limb Enh (ZRS) and the Shh gene, despite 1Mb distance (Lettice et al., 2003). 30146162 chr5 69232175 69234175 CDK7 We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. human High+Lowthroughput Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models 否 leukemia leukemic cell E_02_0459 RT-PCR,ChIP-seq,weston blot We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. Immunohistochemical staining We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. RT-PCR,ChIP-seq,weston blot CDK7,CDK9 We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis.;We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. 30143575 chr9 973683 975683 DMRT3 We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016). human High+Lowthroughput DMRT5, DMRT3, and EMX2 Cooperatively Repress Gsx2 at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors 否 Telencephalic developmental defects progenitor cell E_02_0460 RNA SEQ, QRT PCR, statistical analysis, immunofluorescence staining, gene knockdown We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016). Immunohistochemical staining We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016). RNA-seq,qRT-PCR,统计分析,免疫荧光染色,基因敲降 DMRT3,GSX2,DMRTA2 We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016).;We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016).;We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Related to this study, a loss-of-function mutation in the human DMRT5/DMRTA2 gene has been found to be associated with microcephaly (Urquhart et al., 2016). 30139998 chr20 30244800 30316534 RNF2 Here, we show that RNF2, encoding RING1B, and canonical PRC1 (cPRC1) genes are overexpressed in breast cancer. BMI1, encoding for PCGF4, is the best studied PRC1 gene in cancer to date. human Low+High throughput Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms 否 Breast Cancer mammary gland epithelial cell E_02_0461 ChIP-qPCR,ChIP-seq,Luciferase Reporter Assay In contrast to the broad RING1B ChIP-seq signals in pluripotent cells, RING1B peaks in the breast cell lines were narrow, resembling ChIP-seq signals of transcription factors. Therefore, we assessed whether RING1B is recruited to specific transcription factor-binding sites at SEs. Super-Enhancer -- qRT-PCR BCL-XL/S,BCL2L,BCLX,Bcl-X,PPP1R52 RING1B regulates Enhancer activity and gene transcription not only by promoting the expression of oncogenes but also by regulating chromatin accessibility. ATAC-seq RING1B was recruited to regions targeted by transcription factors and its depletion deregulated breast cancer signaling pathways as well as FOXA1 and ERα localization to chromatin, we next hypothesized that RING1B regulates transcriptional programs in breast cancer by orchestrating chromatin accessibility. To test this, we performed transposase-accessible chromatin sequencing (ATAC-seq)35 in RING1B-depleted cells.These results indicate that RING1B depletion affects chromatin accessibility at enhancer regions. BAP-1,BAP1,DING,HIPI3,RING1B,RING2 ChIP-qPCR -- -- BCL2L1,BCL2L1,BCL2L1 RNF2,RNF2,RNF2 Indeed,we observed RING1B recruitment at SE regions near BCL2L1 in MDA-MB-231 and ESR1 in T47D23.;Indeed,we observed RING1B recruitment at SE regions near BCL2L1 in MDA-MB-231 and ESR1 in T47D23.;Indeed,we observed RING1B recruitment at SE regions near BCL2L1 in MDA-MB-231 and ESR1 in T47D23. RING1B, H3K27me3 and H3K27ac ChIP-qPCR of RIN1GB-containing enhancers in control and RING1B-depleted T47D cells. IgG antibody was used as a negative control. As additional control, RING1B ChIP-qPCR were performed using a different RING1B antibody from the one used for ChIP-seq.;RING1B, H3K27me3 and H3K27ac ChIP-qPCR of RIN1GB-containing enhancers in control and RING1B-depleted T47D cells. IgG antibody was used as a negative control. As additional control, RING1B ChIP-qPCR were performed using a different RING1B antibody from the one used for ChIP-seq.;RING1B, H3K27me3 and H3K27ac ChIP-qPCR of RIN1GB-containing enhancers in control and RING1B-depleted T47D cells. IgG antibody was used as a negative control. As additional control, RING1B ChIP-qPCR were performed using a different RING1B antibody from the one used for ChIP-seq. 30139328 chr18 38066274 38068274 Hdac3 Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. mouse High+Lowthroughput Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation 否 leukemia K562 cell E_02_0462 PCR, pro SEQ, gro SEQ, nascent RNA sequencing analysis, chip seq Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. Immunohistochemical staining Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. PCR,PRO-seq,GRO-seq,新生RNA测序分析,ChIP-seq Hdac3 Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. 30138574 chr1 161763471 161765471 ATF6 Furthermore, 4-PBA diminished the expression32 of ERS markers (GRP78, CHOP, PERK, ATF6 and IRE1α) in vital organs of AP rats. human High+Lowthroughput Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis 否 acute pancreatitis Beta cell E_02_0463 Real time PCR, immunofluorescence staining, statistical analysis Furthermore, 4-PBA diminished the expression32 of ERS markers (GRP78, CHOP, PERK, ATF6 and IRE1α) in vital organs of AP rats. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, 4-PBA diminished the expression32 of ERS markers (GRP78, CHOP, PERK, ATF6 and IRE1α) in vital organs of AP rats. Immunohistochemical staining Furthermore, 4-PBA diminished the expression32 of ERS markers (GRP78, CHOP, PERK, ATF6 and IRE1α) in vital organs of AP rats. real-time PCR,免疫荧光染色,统计分析 ATF6 Furthermore, 4-PBA diminished the expression32 of ERS markers (GRP78, CHOP, PERK, ATF6 and IRE1α) in vital organs of AP rats. 30137413 chr21 37362767 37364767 DYRK1A DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. human High+Lowthroughput DYRK1A interacts with histone acetyl transferase p300 and CBP and localizes to enhancers 否 Mental retardation, microcephaly E_02_0464 Chip SEQ, RT qPCR, statistical analysis, Weston blot, gene knockdown DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. Immunohistochemical staining DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. ChIP-Seq,RT-qPCR,统计分析,weston blot,基因敲降 DYRK1A DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. 30135326 chr8 132864317 132866317 TG Rg1 significantly reduced liver weight, serum alanine aminotransferase (A LT), aspartate aminotransferase (AST), triglyceride (TG), liver fr ee fatty acids (FFAs) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. human High+Lowthroughput Ginsenoside Rg1 Protects against Non-alcoholic Fatty Liver Disease by Ameliorating Lipid Peroxidation, Endoplasmic Reticulum Stress, and Inflammasome Activation 否 Non alcoholic fatty liver disease (NaF LD), liver fibrosis, cirrhosis, hepatocellular carcinoma B cell E_02_0465 QPCR, ELISA, Weston blot, statistical analysis Rg1 significantly reduced liver weight, serum alanine aminotransferase (A LT), aspartate aminotransferase (AST), triglyceride (TG), liver fr ee fatty acids (FFAs) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Rg1 significantly reduced liver weight, serum alanine aminotransferase (A LT), aspartate aminotransferase (AST), triglyceride (TG), liver fr ee fatty acids (FFAs) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. Immunohistochemical staining Rg1 significantly reduced liver weight, serum alanine aminotransferase (A LT), aspartate aminotransferase (AST), triglyceride (TG), liver fr ee fatty acids (FFAs) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. qPCR,ELISA,weston blot,统计分析 TG Rg1 significantly reduced liver weight, serum alanine aminotransferase (A LT), aspartate aminotransferase (AST), triglyceride (TG), liver fr ee fatty acids (FFAs) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. 30132536 chr6 31572566 31574566 TNF TRAIL has reduced toxicicity compared with other members of the tumor necrosis factor (TNF) protein family, such as TNFα and Fas ligand (CD95L) (3). Pre-clinical trials have determined that TRAIL effectively inhibits tumor growth without inducing toxicity in both mice and non-human primates (4,5). human High+Lowthroughput 3?Bromopyruvate sensitizes human breast cancer cells to TRAIL?induced apoptosis via the phosphorylated AMPK?mediated upregulation of DR5 否 mammary cancer MCF-7 cell E_02_0466 ATP quantification, Weston blot, statistical analysis TRAIL has reduced toxicicity compared with other members of the tumor necrosis factor (TNF) protein family, such as TNFα and Fas ligand (CD95L) (3). Pre-clinical trials have determined that TRAIL effectively inhibits tumor growth without inducing toxicity in both mice and non-human primates (4,5). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TRAIL has reduced toxicicity compared with other members of the tumor necrosis factor (TNF) protein family, such as TNFα and Fas ligand (CD95L) (3). Pre-clinical trials have determined that TRAIL effectively inhibits tumor growth without inducing toxicity in both mice and non-human primates (4,5). Immunohistochemical staining TRAIL has reduced toxicicity compared with other members of the tumor necrosis factor (TNF) protein family, such as TNFα and Fas ligand (CD95L) (3). Pre-clinical trials have determined that TRAIL effectively inhibits tumor growth without inducing toxicity in both mice and non-human primates (4,5). ATP quantification,weston blot,统计分析 TNF TRAIL has reduced toxicicity compared with other members of the tumor necrosis factor (TNF) protein family, such as TNFα and Fas ligand (CD95L) (3). Pre-clinical trials have determined that TRAIL effectively inhibits tumor growth without inducing toxicity in both mice and non-human primates (4,5). 30131420 chr12 106988606 106990606 CRY1 he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. human High+Lowthroughput Photoexcited CRYPTOCHROME1 Interacts with Dephosphorylated BES1 to Regulate Brassinosteroid Signaling and Photomorphogenesis in Arabidopsis 否 E_02_0467 BiFC Assays,Co-IP Assays,RT-qPCR,ChIP-qPCR,RNA-Seq,weston blot he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. Immunohistochemical staining he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. BiFC Assays,Co-IP Assays,RT-qPCR,ChIP-qPCR,RNA-Seq,weston blot CRY1,CRY2,COP1 he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. ;he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. ;he signaling mechanism by which Arabidopsis thaliana cryptochromes CRY1 and CRY2 promote photomorphogenesis involves direct interactions with COP1, a RING motif-containing E3 ubiquitin ligase, and its enhancer SPA1. 30131250 chr7 148804336 148806336 EZH2 Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. human High+Lowthroughput microRNA-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant cell proliferation in human glioma 否 Gliomas Glioma cell E_02_0468 qRT-PCR,weston blot, Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. Immunohistochemical staining Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. qRT-PCR,weston blot, EZH2,PHF19 Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a.;Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. 30130256 chr11 98040271 98042271 Med1 Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. mouse High+Lowthroughput Super-enhancers maintain renin-expressing cell identity and memory to preserve multi-system homeostasis 否 As4.1 cell E_02_0469 QRT PCR, ATAC SEQ, chip SEQ, RNA SEQ, statistical analysis Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. Immunohistochemical staining Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. qRT-PCR,ATAC-Seq,ChIP-Seq,RNA-Seq,统计分析 Med1 Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. 30127357 chr17 71648774 71650774 Smchd1 Structural maintenance of chromosomes hinge domain contain- ing 1 (Smchd1) is a noncanonical SMC protein12 that is similar to the canonical SMC proteins13 15 in that it dimerizes and interacts with nucleic acids through its hinge domain 16,17 . At all Smchd1 targets, chromosome conformation at differ- ent scales plays a role in regulating gene expression. mouse High+Lowthroughput Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters 是 293 cell E_02_0470 Chip SEQ, immunofluorescence staining, RT qPCR, Weston blot Structural maintenance of chromosomes hinge domain contain- ing 1 (Smchd1) is a noncanonical SMC protein12 that is similar to the canonical SMC proteins13 15 in that it dimerizes and interacts with nucleic acids through its hinge domain 16,17 . At all Smchd1 targets, chromosome conformation at differ- ent scales plays a role in regulating gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Structural maintenance of chromosomes hinge domain contain- ing 1 (Smchd1) is a noncanonical SMC protein12 that is similar to the canonical SMC proteins13 15 in that it dimerizes and interacts with nucleic acids through its hinge domain 16,17 . At all Smchd1 targets, chromosome conformation at differ- ent scales plays a role in regulating gene expression. Immunohistochemical staining Structural maintenance of chromosomes hinge domain contain- ing 1 (Smchd1) is a noncanonical SMC protein12 that is similar to the canonical SMC proteins13 15 in that it dimerizes and interacts with nucleic acids through its hinge domain 16,17 . At all Smchd1 targets, chromosome conformation at differ- ent scales plays a role in regulating gene expression. ChIP-seq,免疫荧光染色,RT-qPCR,weston blot Smchd1 Structural maintenance of chromosomes hinge domain contain- ing 1 (Smchd1) is a noncanonical SMC protein12 that is similar to the canonical SMC proteins13 15 in that it dimerizes and interacts with nucleic acids through its hinge domain 16,17 . At all Smchd1 targets, chromosome conformation at differ- ent scales plays a role in regulating gene expression. 30127245 chr3 49826074 49828074 TRAIP TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. human High+Lowthroughput In Vitro Inhibitory Mechanism Effect of TRAIP on the Function of TRAF2 Revealed by Characterization of Interaction Domains 否 B cell E_02_0471 Real time PCR, mals, native PAGE shift assay TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. Immunohistochemical staining TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. Real-Time PCR,MALS,Native-PAGE转移分析 TRAIP,TRAF2,TRAF1 TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. ;TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. ;TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling. 30126893 chr10 8042438 8044438 GATA3 Haploid deficiency of the human GATA3 gene leads to a dominantly inherited condition known as HDR (hypoparathyroidism, neural sensory deafness, and renal defect) syndrome (12), underscoring a prominent role for GATA3 in specifying normal developmental programing in the affected tissues. human High+Lowthroughput A Gata3 3' Distal Otic Vesicle Enhancer Directs Inner Ear-Specific Gata3 Expression 是 Neurosensory deafness E_02_0472 PCR,Histological analysis Haploid deficiency of the human GATA3 gene leads to a dominantly inherited condition known as HDR (hypoparathyroidism, neural sensory deafness, and renal defect) syndrome (12), underscoring a prominent role for GATA3 in specifying normal developmental programing in the affected tissues. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Haploid deficiency of the human GATA3 gene leads to a dominantly inherited condition known as HDR (hypoparathyroidism, neural sensory deafness, and renal defect) syndrome (12), underscoring a prominent role for GATA3 in specifying normal developmental programing in the affected tissues. Immunohistochemical staining Haploid deficiency of the human GATA3 gene leads to a dominantly inherited condition known as HDR (hypoparathyroidism, neural sensory deafness, and renal defect) syndrome (12), underscoring a prominent role for GATA3 in specifying normal developmental programing in the affected tissues. PCR,Histological analysis GATA3 Haploid deficiency of the human GATA3 gene leads to a dominantly inherited condition known as HDR (hypoparathyroidism, neural sensory deafness, and renal defect) syndrome (12), underscoring a prominent role for GATA3 in specifying normal developmental programing in the affected tissues. 30126161 chr8 84014206 84016206 Ucp1 H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. mouse adipose High+Lowthroughput β-adrenergic Receptor Stimulation Revealed a Novel Regulatory Pathway via Suppressing Histone Deacetylase 3 to Induce Uncoupling Protein 1 Expression in Mice Beige Adipocyte 否 Obesity E_02_0473 Real time PCR, chromatin immunoprecipitation (chip), statistical analysis, Weston blot H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. Immunohistochemical staining H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. real-time PCR,Chromatin Immunoprecipitation (ChIP) ,统计分析,weston blot Ucp1 H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. 30125982 chr10 30705623 30707623 Hey2 Hairy and enhancer of split related with YRPW motif 2 (Hey2), also known as cardiovascular helix loop helix factor 1 (CHF1), is a member of the hairy and enhancer of split related (HESR) family of basic helix loop helix (bHLH) type transcription factors.22 mouse High+Lowthroughput microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis 否 Chronic periapical periodontitis (CAP) MC3T3-E1 cell E_02_0474 Real ‐ time PCR, ELISA, Weston blot, chromatin immunoprecipitation (chip) Hairy and enhancer of split related with YRPW motif 2 (Hey2), also known as cardiovascular helix loop helix factor 1 (CHF1), is a member of the hairy and enhancer of split related (HESR) family of basic helix loop helix (bHLH) type transcription factors.22 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Hairy and enhancer of split related with YRPW motif 2 (Hey2), also known as cardiovascular helix loop helix factor 1 (CHF1), is a member of the hairy and enhancer of split related (HESR) family of basic helix loop helix (bHLH) type transcription factors.22 Immunohistochemical staining Hairy and enhancer of split related with YRPW motif 2 (Hey2), also known as cardiovascular helix loop helix factor 1 (CHF1), is a member of the hairy and enhancer of split related (HESR) family of basic helix loop helix (bHLH) type transcription factors.22 Real‐time PCR,ELISA,weston blot,染色质免疫沉淀(ChIP) Hey2 Hairy and enhancer of split related with YRPW motif 2 (Hey2), also known as cardiovascular helix loop helix factor 1 (CHF1), is a member of the hairy and enhancer of split related (HESR) family of basic helix loop helix (bHLH) type transcription factors.22 30125275 chr17 42310564 42312564 STAT3 Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. human High+Lowthroughput The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR 否 A549 cell E_02_0475 ELISA, Weston blot, statistical analysis, immunofluorescence light staining Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. Immunohistochemical staining Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. ELISA,weston blot,统计分析,免疫荧光光染色 STAT3 Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. 30124855 chr1 145667850 145669850 PDZK1 siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. human High+Lowthroughput A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression 是 rs1967017,rs1471633 hyperuricemia HEK293 cell E_02_0476 Quantitative PCR, immunoblot analysis, chip PCR, statistical analysis, Weston blot siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Immunohistochemical staining siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Quantitative PCR,Immunoblot analysis, ChIP-PCR,统计分析,weston blot PDZK1,HNF4A siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. ;siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. 30122536 chr8 144288649 144290649 HSF1 We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins. human High+Lowthroughput Architectural Proteins and Pluripotency Factors Cooperate to Orchestrate the Transcriptional Response of hESCs to Temperature Stress 否 embryonic stem cell E_02_0477 EU-seq,HiChIP,ChIP-Seq,ATAC-seq,APA metaplot analysis We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins. Immunohistochemical staining We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins. EU-seq,HiChIP,ChIP-Seq,ATAC-seq,APA metaplot analysis HSF1,NANOG,KLF4,RAD21 We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins.;We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins.;We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins.;We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4, accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins. 30119690 chr16 86422446 86426834 FOXF1 Conclusions Our study elucidates a novel cascade mediated by AP-1 and FOXF1 that regulates oncogene-induced senescence and further demonstrates the power of CRISPR-based functional genomic screens in deciphering the function of non-coding regulatory elements in the genome. human Low+High throughput Functional CRISPR screen identifies AP1-associated enhancer regulating FOXF1 to modulate oncogene-induced senescence 否 -- E_02_0478 ChIP-seq,Luciferase Reporter Assay,CRISPR/Cas9 Notably, two of these five sgRNAs,sgRNAs-AP169 and sgRNA-AP171, are independent sgRNAs that target the same enhancer region,hence increasing the confidence that these are true-positive hits. ENCODE ChIP-seq data confirmed a strong binding of both FOS and JUN to this region. Enhancer CRISPR/Cas9 qRT-PCR ACDMPV,FKHL5,FREAC1 We identify FOXF1 as the gene regulated by this enhancer and demonstrate that FOXF1 mediates EnhAP1-OIS1 effect on the senescence phenotype. qRT-PCR,Western blot the physical interactions between EnhAP1-OIS1 and the promoter region of FOXF1 were significantly stronger , suggesting a robust transcriptional regulation of EnhAP1-OIS1. AP-1,AP1,c-Jun,cJUN,p39 CRISPR/Cas9,Luciferase Reporter Assay -- -- FOXF1 JUN Furthermore,we identified FOXF1 as the tar_x0002_get gene of this Enhancer and demonstrated that it regu_x0002_lates the senescence phenotype. We thus constructed a CRISPR-Cas9 sgRNA library designed to target senescence-induced Enhancers that are putatively regulated by AP-1 and used it in a functional screen.That screen was confined to regions that are directly bound by p53 as detected by p53 chromatin immunoprecipitation-sequencing (ChIP-seq) analysis and therefore missed Enhancers that are critical for OIS enforcement and are regulated by other TFs, in either a p53-dependent or -independent manner. 30115916 chr1 175705483 175707483 Exo1 Although, we previously confirmed that the overexpression of exonuclease 1 (Exo1) enhanced the efficiency of PITCh knock-in9, we attempted to enhance the efficiency further to secure robust gene knock-ins at various genomic loci. We newly identified CtIP as a strong MMEJ enhancer by genetic screening (Supplementary Fig. 1). mouse High+Lowthroughput Biased genome editing using the local accumulation of DSB repair molecules system 是 stem cell E_02_0479 Flow cytometry, statistical analysis, gene knockdown, immunofluorescence staining Although, we previously confirmed that the overexpression of exonuclease 1 (Exo1) enhanced the efficiency of PITCh knock-in9, we attempted to enhance the efficiency further to secure robust gene knock-ins at various genomic loci. We newly identified CtIP as a strong MMEJ enhancer by genetic screening (Supplementary Fig. 1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Although, we previously confirmed that the overexpression of exonuclease 1 (Exo1) enhanced the efficiency of PITCh knock-in9, we attempted to enhance the efficiency further to secure robust gene knock-ins at various genomic loci. We newly identified CtIP as a strong MMEJ enhancer by genetic screening (Supplementary Fig. 1). Immunohistochemical staining Although, we previously confirmed that the overexpression of exonuclease 1 (Exo1) enhanced the efficiency of PITCh knock-in9, we attempted to enhance the efficiency further to secure robust gene knock-ins at various genomic loci. We newly identified CtIP as a strong MMEJ enhancer by genetic screening (Supplementary Fig. 1). 流式细胞术,统计分析,基因敲降,免疫荧光染色 Exo1 Although, we previously confirmed that the overexpression of exonuclease 1 (Exo1) enhanced the efficiency of PITCh knock-in9, we attempted to enhance the efficiency further to secure robust gene knock-ins at various genomic loci. We newly identified CtIP as a strong MMEJ enhancer by genetic screening (Supplementary Fig. 1). 30110655 chrX 20724142 20726142 Syn1 The six elements included the human cytomegalovirus immediate early core promoter element (hCPE), three synthetic enhancer element (SEE1, SEE2, Syn1), human cytomegalovirus immediate early enhancer (hCMV-IEE), and a regulatory element isolated from CHO-K1 genomic DNA (C77). mouse High+Lowthroughput Enhanced transgene expression using cis-acting elements combined with the EF1 promoter in a mammalian expression system 否 E_02_0480 ELISA, real time (q) PCR analyses, statistical analysis The six elements included the human cytomegalovirus immediate early core promoter element (hCPE), three synthetic enhancer element (SEE1, SEE2, Syn1), human cytomegalovirus immediate early enhancer (hCMV-IEE), and a regulatory element isolated from CHO-K1 genomic DNA (C77). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The six elements included the human cytomegalovirus immediate early core promoter element (hCPE), three synthetic enhancer element (SEE1, SEE2, Syn1), human cytomegalovirus immediate early enhancer (hCMV-IEE), and a regulatory element isolated from CHO-K1 genomic DNA (C77). Immunohistochemical staining The six elements included the human cytomegalovirus immediate early core promoter element (hCPE), three synthetic enhancer element (SEE1, SEE2, Syn1), human cytomegalovirus immediate early enhancer (hCMV-IEE), and a regulatory element isolated from CHO-K1 genomic DNA (C77). ELISA,Real-time (q)PCR analyses,统计分析 Syn1 The six elements included the human cytomegalovirus immediate early core promoter element (hCPE), three synthetic enhancer element (SEE1, SEE2, Syn1), human cytomegalovirus immediate early enhancer (hCMV-IEE), and a regulatory element isolated from CHO-K1 genomic DNA (C77). 30109252 chr20 5112272 5114272 PCNA PCNA human High+Lowthroughput Gankyrin Promotes Tumor-Suppressor Protein Degradation to Drive Hepatocyte Proliferation 否 Hepatocellular carcinoma Huh6 cell E_02_0481 RT-PCR, Weston blot, statistical analysis PCNA Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PCNA Immunohistochemical staining PCNA RT-PCR,weston blot,统计分析 PCNA PCNA 30107177 chr10 101128610 101130610 TLX1 Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. human High+Lowthroughput Cooperative Enhancer Activation by TLX1 and STAT5 Drives Development of NUP214-ABL1/TLX1-Positive T Cell Acute Lymphoblastic Leukemia 否 T-cell acute lymphoblastic leukemia E_02_0482 QRT PCR, RNA SEQ, chip SEQ, fast ATAC SEQ, Weston blot, flow cytometry, statistical analysis Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. Immunohistochemical staining Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. qRT-PCR,RNA-seq,ChIP-seq,Fast-ATAC-seq,weston blot,流式细胞术,统计分析 TLX1,MYC,BCL2 Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. ;Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. ;Our data show that TLX1 and STAT5 directly cooperate at the transcriptional level through activation of enhancer regions of key proto-oncogenes such as MYC and BCL2. 30106596 chr5 88714837 88716837 MEF2C MEF2 (myocyte enhancer factor 2) is a transcription factor that regulates multiple genes that are important during cardiovascular development and for vascular homeostasis (1), with MEF2C known to play a crucial role in regulating endothelial integrity, survival, and angiogenesis (2). Some of the results of these studies have been previously reported in the form of an abstract (5). Methods To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a tamoxifen-responsive Cdh5 promoter driven Cre recombinase crossed to mice with Mef2cfl/fl alleles (henceforth called Mef2cECKO mice) (6, 7). human High+Lowthroughput Therapeutic Engagement of the Histone Deacetylase IIA-Myocyte Enhancer Factor 2 Axis Improves Experimental Pulmonary Hypertension 否 Pulmonary arterial hypertension endothelial cell E_02_0483 Flow cytometry, immunofluorescence light staining MEF2 (myocyte enhancer factor 2) is a transcription factor that regulates multiple genes that are important during cardiovascular development and for vascular homeostasis (1), with MEF2C known to play a crucial role in regulating endothelial integrity, survival, and angiogenesis (2). Some of the results of these studies have been previously reported in the form of an abstract (5). Methods To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a tamoxifen-responsive Cdh5 promoter driven Cre recombinase crossed to mice with Mef2cfl/fl alleles (henceforth called Mef2cECKO mice) (6, 7). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEF2 (myocyte enhancer factor 2) is a transcription factor that regulates multiple genes that are important during cardiovascular development and for vascular homeostasis (1), with MEF2C known to play a crucial role in regulating endothelial integrity, survival, and angiogenesis (2). Some of the results of these studies have been previously reported in the form of an abstract (5). Methods To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a tamoxifen-responsive Cdh5 promoter driven Cre recombinase crossed to mice with Mef2cfl/fl alleles (henceforth called Mef2cECKO mice) (6, 7). Immunohistochemical staining MEF2 (myocyte enhancer factor 2) is a transcription factor that regulates multiple genes that are important during cardiovascular development and for vascular homeostasis (1), with MEF2C known to play a crucial role in regulating endothelial integrity, survival, and angiogenesis (2). Some of the results of these studies have been previously reported in the form of an abstract (5). Methods To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a tamoxifen-responsive Cdh5 promoter driven Cre recombinase crossed to mice with Mef2cfl/fl alleles (henceforth called Mef2cECKO mice) (6, 7). 流式细胞术,免疫荧光光染色 MEF2C MEF2 (myocyte enhancer factor 2) is a transcription factor that regulates multiple genes that are important during cardiovascular development and for vascular homeostasis (1), with MEF2C known to play a crucial role in regulating endothelial integrity, survival, and angiogenesis (2). Some of the results of these studies have been previously reported in the form of an abstract (5). Methods To investigate the role of endothelial MEF2 function in the pathogenesis of PH, we generated adult mice with inducible, endothelial-specific deletion of the Mef2c allele, using a tamoxifen-responsive Cdh5 promoter driven Cre recombinase crossed to mice with Mef2cfl/fl alleles (henceforth called Mef2cECKO mice) (6, 7). 30103943 chr14 100776331 100778331 MEG3 Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteo- genesis of hDFSCs. human Osteogenic High+Lowthroughput Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway 否 Dental follicle cells E_02_0484 Gene knockdown, fish, QRT PCR, Weston blot, chromatin immunoprecipitation (chip) - PCR assay, statistical analysis Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteo- genesis of hDFSCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteo- genesis of hDFSCs. Immunohistochemical staining Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteo- genesis of hDFSCs. 基因敲降,FISH, qRT-PCR,weston blot,Chromatin immunoprecipitation (ChIP)-PCR assay,统计分析 MEG3,EZH2 Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteo- genesis of hDFSCs.;Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively regulated osteo- genesis of hDFSCs. 30100087 chr12 1968286 1970286 CACNA1C Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. human High+Lowthroughput Characterization of a Human-Specific Tandem Repeat Associated with Bipolar Disorder and Schizophrenia 是 rs2007044,rs1006737,rs4765905,rs4765913 Bipolar disorder (BD), schizophrenia (SCZ) E_02_0485 Southern blot,PacBio,PCR Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. Immunohistochemical staining Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. Southern blot,PacBio,PCR CACNA1C Genome-wide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. 30099761 chr3 13476946 13478946 HDAC11 Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor- mediated upregulation of TSC2 is unclear. human High+Lowthroughput Upregulation of C/EBPβ and TSC2 by an HDAC inhibitor CG200745 protects heart from DOCA-induced hypertrophy 否 hypertension neural cell E_02_0486 QRT PCR, chromatin immunoprecipitation (chip) assay, Weston blot, statistical analysis Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor- mediated upregulation of TSC2 is unclear. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor- mediated upregulation of TSC2 is unclear. Immunohistochemical staining Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor- mediated upregulation of TSC2 is unclear. qRT-PCR,染色质免疫沉淀(ChIP)测定,weston blot,统计分析 HDAC11,TSC2 Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor- mediated upregulation of TSC2 is unclear.;Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor- mediated upregulation of TSC2 is unclear. 30099093 chr17 42697287 42699287 EZH1 Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. human High+Lowthroughput EZH1 is an antipsychotic-sensitive epigenetic modulator of social and motivational behavior that is dysregulated in schizophrenia 否 Schizophrenia HEK-293 cells E_02_0487 qRT-PCR,RNA seq,weston blot Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. Immunohistochemical staining Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. qRT-PCR,RNA seq,weston blot EZH1 Moreover, the polycomb-associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated in the PFC of schizophrenics. 30098338 chr2 113096632 113098632 IL1RN We specifically targeted regions approximately 4kb, 8kb and 24kb from the IL1RN promoter that do not contain any feature of a regulatory element based on ENCODE H3K27ac and transcription factor ChIP-Seq data (Fig. 1b, Fig.S1a). human High+Lowthroughput Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells 否 cancer K562 cell E_02_0488 Chip qPCR, RT qPCR, chromatin immunoprecipitation reaction, 3-C assay, chip SEQ, DNase - seq We specifically targeted regions approximately 4kb, 8kb and 24kb from the IL1RN promoter that do not contain any feature of a regulatory element based on ENCODE H3K27ac and transcription factor ChIP-Seq data (Fig. 1b, Fig.S1a). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We specifically targeted regions approximately 4kb, 8kb and 24kb from the IL1RN promoter that do not contain any feature of a regulatory element based on ENCODE H3K27ac and transcription factor ChIP-Seq data (Fig. 1b, Fig.S1a). Immunohistochemical staining We specifically targeted regions approximately 4kb, 8kb and 24kb from the IL1RN promoter that do not contain any feature of a regulatory element based on ENCODE H3K27ac and transcription factor ChIP-Seq data (Fig. 1b, Fig.S1a). ChIP-qPCR, RT-qPCR,染色质免疫沉淀反应,3-C Assay,ChIP-Seq,DNase- seq IL1RN We specifically targeted regions approximately 4kb, 8kb and 24kb from the IL1RN promoter that do not contain any feature of a regulatory element based on ENCODE H3K27ac and transcription factor ChIP-Seq data (Fig. 1b, Fig.S1a). 30098214 chr14 100235593 100237593 YY1 Ei and E3 are both required for Igκ gene rearrangement during early stages of B cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3 and Ed. The transcription factor YY1 affects the expression of many genes involved in B cell development, probably by mediating interactions between their enhancers and promoters.Herein, we found that YY1 binds to the E3 enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3 enhancer. human High+Lowthroughput YY1 binds to the E3' enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications 否 B cell E_02_0489 RT ‐ PCR, Weston blot, flow cytometry, statistical analysis, chromatin immunoprecipitation assays, gene knockdown Ei and E3 are both required for Igκ gene rearrangement during early stages of B cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3 and Ed. The transcription factor YY1 affects the expression of many genes involved in B cell development, probably by mediating interactions between their enhancers and promoters.Herein, we found that YY1 binds to the E3 enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3 enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ei and E3 are both required for Igκ gene rearrangement during early stages of B cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3 and Ed. The transcription factor YY1 affects the expression of many genes involved in B cell development, probably by mediating interactions between their enhancers and promoters.Herein, we found that YY1 binds to the E3 enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3 enhancer. Immunohistochemical staining Ei and E3 are both required for Igκ gene rearrangement during early stages of B cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3 and Ed. The transcription factor YY1 affects the expression of many genes involved in B cell development, probably by mediating interactions between their enhancers and promoters.Herein, we found that YY1 binds to the E3 enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3 enhancer. RT‐PCR,weston blot,流式细胞术,统计分析,Chromatin immunoprecipitation assays,基因敲降 YY1,TCF3 Ei and E3 are both required for Igκ gene rearrangement during early stages of B cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3 and Ed. The transcription factor YY1 affects the expression of many genes involved in B cell development, probably by mediating interactions between their enhancers and promoters.Herein, we found that YY1 binds to the E3 enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3 enhancer. ;Ei and E3 are both required for Igκ gene rearrangement during early stages of B cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3 and Ed. The transcription factor YY1 affects the expression of many genes involved in B cell development, probably by mediating interactions between their enhancers and promoters.Herein, we found that YY1 binds to the E3 enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3 enhancer. 30096897 chr1 180629337 180631337 XPR1 The E-MLVs use the CAT-1 receptor [4], and all X/P-MLVs use the XPR1 receptor [5,6,7]. There are functionally distinct XPR1 variants in the genus Mus, but the majority of mouse strains carry Xpr1n, which allows for the infection of P-MLVs but not X-MLVs [8]. human High+Lowthroughput Xenotropic Mouse Gammaretroviruses Isolated from Pre-Leukemic Tissues Include a Recombinant 否 leukemia E_02_0490 PCR The E-MLVs use the CAT-1 receptor [4], and all X/P-MLVs use the XPR1 receptor [5,6,7]. There are functionally distinct XPR1 variants in the genus Mus, but the majority of mouse strains carry Xpr1n, which allows for the infection of P-MLVs but not X-MLVs [8]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The E-MLVs use the CAT-1 receptor [4], and all X/P-MLVs use the XPR1 receptor [5,6,7]. There are functionally distinct XPR1 variants in the genus Mus, but the majority of mouse strains carry Xpr1n, which allows for the infection of P-MLVs but not X-MLVs [8]. Immunohistochemical staining The E-MLVs use the CAT-1 receptor [4], and all X/P-MLVs use the XPR1 receptor [5,6,7]. There are functionally distinct XPR1 variants in the genus Mus, but the majority of mouse strains carry Xpr1n, which allows for the infection of P-MLVs but not X-MLVs [8]. PCR XPR1 The E-MLVs use the CAT-1 receptor [4], and all X/P-MLVs use the XPR1 receptor [5,6,7]. There are functionally distinct XPR1 variants in the genus Mus, but the majority of mouse strains carry Xpr1n, which allows for the infection of P-MLVs but not X-MLVs [8]. 30085311 chr19 19142788 19144788 MEF2B Broiler growth is related to skeletal muscle develop- ment which is regulated by myogenic regulatory factors including myogenic differentiation factor 1 (MyoD1), myogenic factor 5 (Myf5), muscle regulator 4 (MRF4), myogenin (MyoG), myocyte enhancer factor 2 family of transcription factors (MEF2A, B, C, D), as well as myostatin (MSTN) (Hennebry et al., 2009; Townley-Tilson et al., 2010). human High+Lowthroughput Betaine improves the growth performance and muscle growth of partridge shank broiler chickens via altering myogenic gene expression and insulin-like growth factor-1 signaling pathway 否 C2C12 cell E_02_0491 Real time PCR, IGF-1 enzyme linked immunosorbent assay, Western blot, and statistical analysis Broiler growth is related to skeletal muscle develop- ment which is regulated by myogenic regulatory factors including myogenic differentiation factor 1 (MyoD1), myogenic factor 5 (Myf5), muscle regulator 4 (MRF4), myogenin (MyoG), myocyte enhancer factor 2 family of transcription factors (MEF2A, B, C, D), as well as myostatin (MSTN) (Hennebry et al., 2009; Townley-Tilson et al., 2010). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Broiler growth is related to skeletal muscle develop- ment which is regulated by myogenic regulatory factors including myogenic differentiation factor 1 (MyoD1), myogenic factor 5 (Myf5), muscle regulator 4 (MRF4), myogenin (MyoG), myocyte enhancer factor 2 family of transcription factors (MEF2A, B, C, D), as well as myostatin (MSTN) (Hennebry et al., 2009; Townley-Tilson et al., 2010). Immunohistochemical staining Broiler growth is related to skeletal muscle develop- ment which is regulated by myogenic regulatory factors including myogenic differentiation factor 1 (MyoD1), myogenic factor 5 (Myf5), muscle regulator 4 (MRF4), myogenin (MyoG), myocyte enhancer factor 2 family of transcription factors (MEF2A, B, C, D), as well as myostatin (MSTN) (Hennebry et al., 2009; Townley-Tilson et al., 2010). real-time PCR,IGF-1 Enzyme-Linked Immunosorbent Assay,western blot,统计分析 MEF2B,Myf5 Broiler growth is related to skeletal muscle develop- ment which is regulated by myogenic regulatory factors including myogenic differentiation factor 1 (MyoD1), myogenic factor 5 (Myf5), muscle regulator 4 (MRF4), myogenin (MyoG), myocyte enhancer factor 2 family of transcription factors (MEF2A, B, C, D), as well as myostatin (MSTN) (Hennebry et al., 2009; Townley-Tilson et al., 2010). ;Broiler growth is related to skeletal muscle develop- ment which is regulated by myogenic regulatory factors including myogenic differentiation factor 1 (MyoD1), myogenic factor 5 (Myf5), muscle regulator 4 (MRF4), myogenin (MyoG), myocyte enhancer factor 2 family of transcription factors (MEF2A, B, C, D), as well as myostatin (MSTN) (Hennebry et al., 2009; Townley-Tilson et al., 2010). 30084829 chr14 100776351 100778351 MEG3 In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. human High+Lowthroughput The Dysregulation of the DLK1-MEG3 Locus in Islets From Patients With Type 2 Diabetes Is Mimicked by Targeted Epimutation of Its Promoter With TALE-DNMT Constructs 是 rs3783355 Type 2 diabetes mellitus (T2DM) E_02_0492 ChIP-PCR,4C-Seq,RT-PCR In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. Immunohistochemical staining In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. ChIP-PCR,4C-Seq,RT-PCR MEG3,FOXA2,PDX1 In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. ;In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. ;In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse βTC6 β-cells results in decreased transcription of the maternal transcripts associated with this locus. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. 30082728 chr8 115405258 115407258 TRPS1 We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. human High+Lowthroughput TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells 否 Colon cancer, breast cancer mammary gland epithelial cell E_02_0493 QRT PCR, Western blot, chromatin immunoprecipitation (chip), chip SEQ, 4C SEQ, ATAC SEQ, immunofluorescence staining, statistical analysis We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. Immunohistochemical staining We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. qRT-PCR,western blot,染色质免疫沉淀(ChIP),ChIP-Seq,4C-Seq,ATAC-Seq,免疫荧光染色,统计分析 TRPS1 We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. 30081710 chr6 114617420 114619420 Atg7 Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression. mouse High+Lowthroughput Autophagy controls neonatal myogenesis by regulating the GH-IGF1 system through a NFE2L2- and DDIT3-mediated mechanism 否 C2C12 cell E_02_0494 RT qPCR, Western blot, immunofluorescence staining, statistical analysis Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression. Immunohistochemical staining Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression. RT-qPCR,western blot,免疫荧光染色,统计分析 Atg7,NFE2L2 Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression.;Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions. When we disrupted autophagy, NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) accumulated in muscle and nSCs and negatively modulated DDIT3/CHOP (DNA-damage inducible transcript 3) expression. 30081225 chr5 122060306 122062306 LOX Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/ 21/ 1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. human High+Lowthroughput The effects of subacute inhaled multi-walled carbon nanotube exposure on signaling pathways associated with cholesterol transport and inflammatory markers in the vasculature of wild-type mice 否 Atherosclerosis, coronary artery disease (CAD) B cell E_02_0495 RT-PCR, immunofluorescence staining Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/ 21/ 1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/ 21/ 1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. Immunohistochemical staining Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/ 21/ 1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. RT-PCR,免疫荧光染色 LOX Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/ 21/ 1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. 30080426 chr8 63165731 63167731 YTHDF3 Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. human High+Lowthroughput Expression of circular RNAs during C2C12 myoblast differentiation and prediction of coding potential based on the number of open reading frames and N6-methyladenosine motifs 否 Hepatocellular carcinoma C2C12 cell E_02_0496 QRT-PCR, statistical analysis Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. Immunohistochemical staining Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. QRT-PCR,统计分析 YTHDF3,Myh1,Myh7 Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. ;Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. ;Recently, it was reported that m6A motif was sufficient to drive translation initiation in circRNAs; and m6A motif-driven translation required eukaryotic translation initiation factor 4 gamma 2 (eIF4G2) and m6A reader YTH domain family protein 3 (YTHDF3) in human cells [21]. Myh is divided into different subtypes, and Myh1 is the signature gene of fast-twitch muscle fibers [26], while Myh7 is important for slow-twitch muscle fibers [27]. 30077771 chr4 94934152 94936152 Jun Differential Jun binding near transcription start sites. A) Bar plot showing the proportion of differentially- and commonly-bound Jun sites within 2kb of a TSS whose associated genes are upregulated (left) or downregulated (right) 7 days after sciatic nerve axotomy. mouse High+Lowthroughput The effect of Jun dimerization on neurite outgrowth and motif binding 否 Spinal cord injury HEK E_02_0497 Chip qPCR, chipseq, rnaseq, immunofluorescence staining Differential Jun binding near transcription start sites. A) Bar plot showing the proportion of differentially- and commonly-bound Jun sites within 2kb of a TSS whose associated genes are upregulated (left) or downregulated (right) 7 days after sciatic nerve axotomy. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Differential Jun binding near transcription start sites. A) Bar plot showing the proportion of differentially- and commonly-bound Jun sites within 2kb of a TSS whose associated genes are upregulated (left) or downregulated (right) 7 days after sciatic nerve axotomy. Immunohistochemical staining Differential Jun binding near transcription start sites. A) Bar plot showing the proportion of differentially- and commonly-bound Jun sites within 2kb of a TSS whose associated genes are upregulated (left) or downregulated (right) 7 days after sciatic nerve axotomy. ChIP-qPCR,ChIPseq,RNAseq ,免疫荧光染色 Jun Differential Jun binding near transcription start sites. A) Bar plot showing the proportion of differentially- and commonly-bound Jun sites within 2kb of a TSS whose associated genes are upregulated (left) or downregulated (right) 7 days after sciatic nerve axotomy. 30076309 chr14 100235442 100237442 YY1 The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33. human High+Lowthroughput Regulation of miR-181a expression in T cell aging 否 Chicken pox T cell E_02_0498 Chip PCR, RNA SEQ, ATAC SEQ, statistical analysis, Western blot The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33. Immunohistochemical staining The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33. ChIP-PCR,RNA-seq,ATAC-seq,统计分析,western blot YY1,DUSP6,PTPN22,DUSP5,PTEN The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33.;The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33.;The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33.;The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33.;The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Functionally, it is an intrinsic regulator of the TCR activation threshold by controlling the expression of the cytoplasmic DUSP6 and other negative feedback pathways including PTPN22, SHP2, DUSP5, and SIRT129 31. In addition, a reduced expression of PTEN and associated effects on the AKT-mTORC1 pathways have been described in one, although not confirmed in a second miR-181a/b1-deficient mouse32,33. 30076153 chr11 64724349 64726349 RASGRP2 rASGrp2 activated rAp-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. human Synovial High+Lowthroughput Ectopic RASGRP2 (CalDAG-GEFI) expression in rheumatoid synovium contributes to the development of destructive arthritis 否 Rheumatoid arthritis (RA) Jurkat cell E_02_0499 Real time QRT PCR, Western blot, immunofluorescence staining, immunohistochemistry rASGrp2 activated rAp-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq rASGrp2 activated rAp-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. Immunohistochemical staining rASGrp2 activated rAp-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. real-time qRT-PCR,western blot,免疫荧光染色,免疫组化 RASGRP2 rASGrp2 activated rAp-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. 30071596 chr12 6531860 6533860 GAPDH Another antibody was used to detect GAPDH to confirm equivalent protein loading. human High+Lowthroughput Model Senescent Microglia Induce Disease Related Changes in α-Synuclein Expression and Activity 否 Tumour, Alzheimer's disease (AD) C8-B4 cell E_02_0500 RT-PCR, Western blot, statistical analysis Another antibody was used to detect GAPDH to confirm equivalent protein loading. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Another antibody was used to detect GAPDH to confirm equivalent protein loading. Immunohistochemical staining Another antibody was used to detect GAPDH to confirm equivalent protein loading. RT-PCR,western blot,统计分析 GAPDH Another antibody was used to detect GAPDH to confirm equivalent protein loading. 30066891 chr7 148804782 148806782 EZH2 Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3). The central factors for regulating autophagy are adenosine monophosphate (AMP) kinase (AMPK) and mammalian target of rapamycin (mTOR). human High+Lowthroughput miR?92b promotes autophagy and suppresses viability and invasion in breast cancer by targeting EZH2 否 mammary cancer COS7 cells E_02_0501 Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3). The central factors for regulating autophagy are adenosine monophosphate (AMP) kinase (AMPK) and mammalian target of rapamycin (mTOR). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3). The central factors for regulating autophagy are adenosine monophosphate (AMP) kinase (AMPK) and mammalian target of rapamycin (mTOR). Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3). The central factors for regulating autophagy are adenosine monophosphate (AMP) kinase (AMPK) and mammalian target of rapamycin (mTOR). GFP-LC3 analyses,western blot,RT-qPCR,统计分析 EZH2 Enhancer of zeste homolog 2 (EZH2) is the core enzymatic subunit of polycomb repressor complex 2 and is responsible for the trimethylation of histone 3 on lysine 27 (H3K27me3). The central factors for regulating autophagy are adenosine monophosphate (AMP) kinase (AMPK) and mammalian target of rapamycin (mTOR). 30061199 chr7 34815866 34817866 Cebpa Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Introduction The C/EBPα basic region-leucine zipper transcription factor (TF) regulates myeloid development and transformation (1). Cebpa / mice manifest neonatal lethality due to hypoglycemia, with marked neutropenia but no reduction in splenic B220+ B cells or thymic CD4+ or CD8+ T cells (2). mouse High+Lowthroughput Progression from the Common Lymphoid Progenitor to B/Myeloid PreproB and ProB Precursors during B Lymphopoiesis Requires C/EBPα 否 E_02_0502 Flow cytometry, statistical analysis, PCR Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Introduction The C/EBPα basic region-leucine zipper transcription factor (TF) regulates myeloid development and transformation (1). Cebpa / mice manifest neonatal lethality due to hypoglycemia, with marked neutropenia but no reduction in splenic B220+ B cells or thymic CD4+ or CD8+ T cells (2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Introduction The C/EBPα basic region-leucine zipper transcription factor (TF) regulates myeloid development and transformation (1). Cebpa / mice manifest neonatal lethality due to hypoglycemia, with marked neutropenia but no reduction in splenic B220+ B cells or thymic CD4+ or CD8+ T cells (2). Immunohistochemical staining Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Introduction The C/EBPα basic region-leucine zipper transcription factor (TF) regulates myeloid development and transformation (1). Cebpa / mice manifest neonatal lethality due to hypoglycemia, with marked neutropenia but no reduction in splenic B220+ B cells or thymic CD4+ or CD8+ T cells (2). 流式细胞术,统计分析,PCR Cebpa,TF Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Introduction The C/EBPα basic region-leucine zipper transcription factor (TF) regulates myeloid development and transformation (1). Cebpa / mice manifest neonatal lethality due to hypoglycemia, with marked neutropenia but no reduction in splenic B220+ B cells or thymic CD4+ or CD8+ T cells (2).;Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Introduction The C/EBPα basic region-leucine zipper transcription factor (TF) regulates myeloid development and transformation (1). Cebpa / mice manifest neonatal lethality due to hypoglycemia, with marked neutropenia but no reduction in splenic B220+ B cells or thymic CD4+ or CD8+ T cells (2). 30058478 chr9 107482373 107484373 KLF4 By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions. human High+Lowthroughput Analysis of KLF4 regulated genes in cancer cells reveals a role of DNA methylation in promoter- enhancer interactions 否 Malignant brain tumors glioblastoma multiforme E_02_0503 Statistical analysis of quantitative mass spectrometry, quantitative real-time PCR, Western blot, chromatin immunoprecipitation PCR (chip) - PCR, statistical analysis By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions. Immunohistochemical staining By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions. 定量质谱统计分析,Quantitative real-time PCR,western blot,Chromatin immunoprecipitation PCR (ChIP)-PCR,统计分析 KLF4,BLK,LMO7 By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions.;By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions.;By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions. 30057145 chr1 212683365 212685365 BATF3 RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. human High+Lowthroughput Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma 否 Adult T cell leukemia / lymphoma (ATLL) Adult T-Cell Leukemia/Lymphoma E_02_0504 Q-RT-PCR, chip SEQ, crispr-cas9 screening, immunoblot analysis, Western blot RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. Immunohistochemical staining RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. Q-RT-PCR,ChIP-seq,CRISPR-Cas9筛析,Immunoblot Analysis,western blot BATF3,MYC RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression.;RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. 30057115 chr3 133743395 133745395 TF The cistromes include functional enhancer sites, where TF binding leads to regulation of gene transcription over large genomic distances (Levine et al., 2014). human High+Lowthroughput Diet-Induced Circadian Enhancer Remodeling Synchronizes Opposing Hepatic Lipid Metabolic Processes 否 Obesity (DIO), type 2 diabetes, cardiovascular disease, hypertension, cancer E_02_0505 GRO-seq,Western Blot,ChIP-seq The cistromes include functional enhancer sites, where TF binding leads to regulation of gene transcription over large genomic distances (Levine et al., 2014). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The cistromes include functional enhancer sites, where TF binding leads to regulation of gene transcription over large genomic distances (Levine et al., 2014). Immunohistochemical staining The cistromes include functional enhancer sites, where TF binding leads to regulation of gene transcription over large genomic distances (Levine et al., 2014). GRO-seq,Western Blot,ChIP-seq TF The cistromes include functional enhancer sites, where TF binding leads to regulation of gene transcription over large genomic distances (Levine et al., 2014). 30055251 chr10 96186235 96188235 BLNK Functional studies involving BLNK were first car- ried out in chicken BLNK-deficient DT40 cells, which exhibited the abolishment of phospholipase C-γ2 (PLC-γ2) tyrosine phosphorylation, a calcium mobilization defect, and impaired activation of c-Jun N- terminal kinase (JNK) [4]. After SYK phosphorylates several critical tyrosines (Y72, Y84, Y96, Y178, and Y189), BLNK provides docking sites for intracellular sig- naling molecules including guanine nucleotide exchange factors (VAV), non-catalytic region of tyrosine kinase (NCK), Bruton's tyrosine kinase (BTK), and phospholipase Cγ (PLCγ) [1 3]. human High+Lowthroughput Identification and functional analysis of grouper (Epinephelus coioides) B-cell linker protein BLNK 否 HEK293T E_02_0506 Western blot, immunofluorescence staining Functional studies involving BLNK were first car- ried out in chicken BLNK-deficient DT40 cells, which exhibited the abolishment of phospholipase C-γ2 (PLC-γ2) tyrosine phosphorylation, a calcium mobilization defect, and impaired activation of c-Jun N- terminal kinase (JNK) [4]. After SYK phosphorylates several critical tyrosines (Y72, Y84, Y96, Y178, and Y189), BLNK provides docking sites for intracellular sig- naling molecules including guanine nucleotide exchange factors (VAV), non-catalytic region of tyrosine kinase (NCK), Bruton's tyrosine kinase (BTK), and phospholipase Cγ (PLCγ) [1 3]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Functional studies involving BLNK were first car- ried out in chicken BLNK-deficient DT40 cells, which exhibited the abolishment of phospholipase C-γ2 (PLC-γ2) tyrosine phosphorylation, a calcium mobilization defect, and impaired activation of c-Jun N- terminal kinase (JNK) [4]. After SYK phosphorylates several critical tyrosines (Y72, Y84, Y96, Y178, and Y189), BLNK provides docking sites for intracellular sig- naling molecules including guanine nucleotide exchange factors (VAV), non-catalytic region of tyrosine kinase (NCK), Bruton's tyrosine kinase (BTK), and phospholipase Cγ (PLCγ) [1 3]. Immunohistochemical staining Functional studies involving BLNK were first car- ried out in chicken BLNK-deficient DT40 cells, which exhibited the abolishment of phospholipase C-γ2 (PLC-γ2) tyrosine phosphorylation, a calcium mobilization defect, and impaired activation of c-Jun N- terminal kinase (JNK) [4]. After SYK phosphorylates several critical tyrosines (Y72, Y84, Y96, Y178, and Y189), BLNK provides docking sites for intracellular sig- naling molecules including guanine nucleotide exchange factors (VAV), non-catalytic region of tyrosine kinase (NCK), Bruton's tyrosine kinase (BTK), and phospholipase Cγ (PLCγ) [1 3]. Western blot,免疫荧光染色 BLNK Functional studies involving BLNK were first car- ried out in chicken BLNK-deficient DT40 cells, which exhibited the abolishment of phospholipase C-γ2 (PLC-γ2) tyrosine phosphorylation, a calcium mobilization defect, and impaired activation of c-Jun N- terminal kinase (JNK) [4]. After SYK phosphorylates several critical tyrosines (Y72, Y84, Y96, Y178, and Y189), BLNK provides docking sites for intracellular sig- naling molecules including guanine nucleotide exchange factors (VAV), non-catalytic region of tyrosine kinase (NCK), Bruton's tyrosine kinase (BTK), and phospholipase Cγ (PLCγ) [1 3]. 30051352 chrX 53079604 53081604 TSPYL2 Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). Our group has shown that TSPYL2 directly regulates the transcription of genes for NMDA receptor subunits 2A (Grin2a) and 2B (Grin2b) in mice [9]. human High+Lowthroughput TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons 否 Neuroblastoma E_02_0507 Western blot, immunocytochemistry, hybridization to peptide arrays, chip SEQ, RT qPCR, chip PCR, statistical analysis Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). Our group has shown that TSPYL2 directly regulates the transcription of genes for NMDA receptor subunits 2A (Grin2a) and 2B (Grin2b) in mice [9]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). Our group has shown that TSPYL2 directly regulates the transcription of genes for NMDA receptor subunits 2A (Grin2a) and 2B (Grin2b) in mice [9]. Immunohistochemical staining Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). Our group has shown that TSPYL2 directly regulates the transcription of genes for NMDA receptor subunits 2A (Grin2a) and 2B (Grin2b) in mice [9]. Western Blot,Immunocytochemistry,Hybridization to Peptide Arrays,ChIP-seq,RT-qPCR,ChIP-PCR,统计分析 TSPYL2,EZH2 Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). Our group has shown that TSPYL2 directly regulates the transcription of genes for NMDA receptor subunits 2A (Grin2a) and 2B (Grin2b) in mice [9].;Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. To identify other genes regulated by TSPYL2, here, we showed that Tspyl2 knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). Our group has shown that TSPYL2 directly regulates the transcription of genes for NMDA receptor subunits 2A (Grin2a) and 2B (Grin2b) in mice [9]. 30046953 chr8 94246601 94248601 GEM Our results showed that most of the bulk impurities had been removed, and PA-GRFT could capture PRRSV onto GEM particles. human High+Lowthroughput Surface-displayed porcine reproductive and respiratory syndrome virus from cell culture onto gram-positive enhancer matrix particles 否 Respiratory syndrome MARC-145 cell E_02_0508 SDS-PAGE,western blot Our results showed that most of the bulk impurities had been removed, and PA-GRFT could capture PRRSV onto GEM particles. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our results showed that most of the bulk impurities had been removed, and PA-GRFT could capture PRRSV onto GEM particles. Immunohistochemical staining Our results showed that most of the bulk impurities had been removed, and PA-GRFT could capture PRRSV onto GEM particles. SDS-PAGE,western blot GEM Our results showed that most of the bulk impurities had been removed, and PA-GRFT could capture PRRSV onto GEM particles. 30045748 chr13 55970191 55972191 Pitx1 Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. mouse High+Lowthroughput Functional characterization of enhancer evolution in the primate lineage 是 HepG2 cell E_02_0509 Starr SEQ, chip SEQ, PCR, gene knockdown Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. Immunohistochemical staining Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. STARR-seq,ChIP-seq,PCR,基因敲降 Pitx1,MCM6 Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14].;Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. 30044535 chr2 135836643 135838643 MCM6 Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. human Marrow adipose High+Lowthroughput A Lox/CHOP-10 crosstalk governs osteogenic and adipogenic cell fate by MSCs 否 Obesity, osteoporosis stromal cell of bone marrow E_02_0510 Western blot,Q‐PCR Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. Immunohistochemical staining Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. Western blot,Q‐PCR MCM6 Examples of the former include fruitful investigations of how specific enhancers underlie phenotypic changes, e.g. cis-regulatory changes of the yellow locus affecting Drosophila pigmentation [10, 11], recurrent deletions of a Pitx1 enhancer resulting in the loss of pelvic armor in stickleback [12], and recurrent SNPs in the intron of MCM6, resulting in lactase persistence in humans [13, 14]. 30043530 chr6 16296402 16298402 ATXN1 Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. human High+Lowthroughput Astroglia contribute to the pathogenesis of spinocerebellar ataxia Type 1 (SCA1) in a biphasic, stage-of-disease specific manner 否 Spinocerebellar ataxia type 1 (SCA1), amyotrophic lateral sclerosis (ALS), Huntington's disease (hd), Parkinson's disease, multiple system atrophy (MSA) Astrocyte E_02_0511 Rotarod analysis, quantitative analysis of immunofluorescent staining, Western blot, RT qPCR, statistical analysis Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. Immunohistochemical staining Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. Rotarod analysis,Quantitative Analysis of immunofluorescent staining,Western blot,RT-qPCR,统计分析 ATXN1 Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. 30038553 chr18 59216984 59218984 GRP GRP, glucose-regulated protein 78 kDa. human High+Lowthroughput Tauroursodeoxycholic Acid Alleviates H(2)O(2)-Induced Oxidative Stress and Apoptosis via Suppressing Endoplasmic Reticulum Stress in Neonatal Rat Cardiomyocytes 否 Acute myocardial infarction (MI) cardiac muscle cell (sensu Arthopoda) E_02_0512 Enzyme linked immunosorbent assay, Western blot, flow cytometry, statistical analysis GRP, glucose-regulated protein 78 kDa. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GRP, glucose-regulated protein 78 kDa. Immunohistochemical staining GRP, glucose-regulated protein 78 kDa. Enzyme-Linked Immunosorbent Assay,Western Blot,流式细胞术,统计分析 GRP GRP, glucose-regulated protein 78 kDa. 30037904 chrX 71530600 71532600 OGT Here, we demonstrate the existence of a homeostatic mechanism involving mutual regulation of the O-GlcNAc cycling enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) at the transcriptional level. human High+Lowthroughput Transcriptional regulation of O-GlcNAc homeostasis is disrupted in pancreatic cancer 否 Cancer, diabetes, cardiovascular, neurodegenerative disease, pancreatic cancer PDAC cell E_02_0513 RT–qPCR,ChIP-seq,western blot Here, we demonstrate the existence of a homeostatic mechanism involving mutual regulation of the O-GlcNAc cycling enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) at the transcriptional level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we demonstrate the existence of a homeostatic mechanism involving mutual regulation of the O-GlcNAc cycling enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) at the transcriptional level. Immunohistochemical staining Here, we demonstrate the existence of a homeostatic mechanism involving mutual regulation of the O-GlcNAc cycling enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) at the transcriptional level. RT–qPCR,ChIP-seq,western blot OGT Here, we demonstrate the existence of a homeostatic mechanism involving mutual regulation of the O-GlcNAc cycling enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) at the transcriptional level. 30037417 chr4 186066455 186068455 TLR3 Poly I:C is a synthetic analog of double-stranded RNA which is present in some viruses and is a TLR3 agonist. human High+Lowthroughput Comparison of immunogenicity, efficacy and transcriptome changes of inactivated rabies virus vaccine with different adjuvants 否 rabies BHK-21 cell E_02_0514 ELISA, RFFIT, RT qPCR, statistical analysis Poly I:C is a synthetic analog of double-stranded RNA which is present in some viruses and is a TLR3 agonist. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Poly I:C is a synthetic analog of double-stranded RNA which is present in some viruses and is a TLR3 agonist. Immunohistochemical staining Poly I:C is a synthetic analog of double-stranded RNA which is present in some viruses and is a TLR3 agonist. ELISA,RFFIT,RT-qPCR,统计分析 TLR3 Poly I:C is a synthetic analog of double-stranded RNA which is present in some viruses and is a TLR3 agonist. 30035248 chr8 11673642 11675642 GATA4 GATA4 is a zinc finger transcription factor that is a pioneer factor in various tissues and regulates tissue specific gene regulation. To determine if Runx2 is a direct target of GATA4, chromatin immunoprecipitation (ChIP) was performed, and it demonstrated that GATA4 is recruited to the two Runx2 promoters and an enhancer region. human Skeletal High+Lowthroughput GATA4 Directly Regulates Runx2 Expression and Osteoblast Differentiation 否 cementoblast E_02_0515 Immunohistochemistry, RNA in situ (rnascope), quantitative PCR, statistical analysis GATA4 is a zinc finger transcription factor that is a pioneer factor in various tissues and regulates tissue specific gene regulation. To determine if Runx2 is a direct target of GATA4, chromatin immunoprecipitation (ChIP) was performed, and it demonstrated that GATA4 is recruited to the two Runx2 promoters and an enhancer region. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GATA4 is a zinc finger transcription factor that is a pioneer factor in various tissues and regulates tissue specific gene regulation. To determine if Runx2 is a direct target of GATA4, chromatin immunoprecipitation (ChIP) was performed, and it demonstrated that GATA4 is recruited to the two Runx2 promoters and an enhancer region. Immunohistochemical staining GATA4 is a zinc finger transcription factor that is a pioneer factor in various tissues and regulates tissue specific gene regulation. To determine if Runx2 is a direct target of GATA4, chromatin immunoprecipitation (ChIP) was performed, and it demonstrated that GATA4 is recruited to the two Runx2 promoters and an enhancer region. Immunohistochemistry,RNA in situ (RNAscope),Quantitative PCR,统计分析 GATA4,Runx2 GATA4 is a zinc finger transcription factor that is a pioneer factor in various tissues and regulates tissue specific gene regulation. To determine if Runx2 is a direct target of GATA4, chromatin immunoprecipitation (ChIP) was performed, and it demonstrated that GATA4 is recruited to the two Runx2 promoters and an enhancer region. ;GATA4 is a zinc finger transcription factor that is a pioneer factor in various tissues and regulates tissue specific gene regulation. To determine if Runx2 is a direct target of GATA4, chromatin immunoprecipitation (ChIP) was performed, and it demonstrated that GATA4 is recruited to the two Runx2 promoters and an enhancer region. 30033119 chr8 38291071 38304326 TF Enhancer function requires transcription factor (TF) binding and correlates with histone modifications. Although active enhancers associate with TFs, only a minority of regions marked by NANOG, OCT4, H3K27ac, and H3K4me1 function as enhancers, with activity markedly changing under naive versus primed culture conditions. human Low+High throughput Functional Dissection of the Enhancer Repertoire in Human Embryonic Stem Cells 否 -- Embryonic stem cell E_02_0516 ChIP-STARR-seq Visual inspection of selected genomic regions illustrates the broad spectrum of enhancer activity measured by ChIP-STARR-seq. For instance, ChIP-seq for NANOG indicates two strong binding sites up- and downstream of SOX2, but only the downstream binding site resulted in ChIP-STARR-seq RNA in excess of plasmid abundance. Super-Enhancer CRISPR/Cas9 Luciferase Reporter Assay,qRT-PCR BFGFR,CD331,CEK,ECCL,FGFBR,FGFR-1,FLG,FLT-2,FLT2,HBGFR,HH2,HRTFDS,KAL2,N-SAM,OGD,bFGF-R-1 Although transposable elements associate with putative enhancers, only some exhibit activity. Luciferase Reporter Assay,CRISPR/Cas9 Luciferase assays confirmed spatially restricted Enhancer activity of DNA in the neighborhood of the central active region of the FGFR1 SE OCT3,OCT4,OTF-3,OTF3,OTF4,Oct-3,Oct-4,ANOP3,MCOPS3,NANOG ChIP-qPCR -- -- FGFR1,FGFR1 POU5F1 ,POU5F1 Luciferase assays confirmed spatially restricted Enhancer activity of DNA in the neighborhood of the central active region of the FGFR1 SE.;Luciferase assays confirmed spatially restricted Enhancer activity of DNA in the neighborhood of the central active region of the FGFR1 SE. To investigate the functional potential of enhancers in ESCs, we first focused on primed H9 ESCs (Figures S1A and S1B) and performed ChIP for NANOG, OCT4, H3K4me1 and H3K27ac.ChIP-qPCR and ChIP-seq were similar to previous results (Figures S1C and 1D).Applying this threshold to regions bound by NANOG, OCT4, H3K4me1, H3K27ac, or combinations of these factors indicates that only a minority of ChIP-seq peaks showed enhancer activity (Figure 2D and S3C), with regions bound by OCT4 having the highest proportion of high activity enhancers.;To investigate the functional potential of enhancers in ESCs, we first focused on primed H9 ESCs (Figures S1A and S1B) and performed ChIP for NANOG, OCT4, H3K4me1 and H3K27ac.ChIP-qPCR and ChIP-seq were similar to previous results (Figures S1C and 1D).Applying this threshold to regions bound by NANOG, OCT4, H3K4me1, H3K27ac, or combinations of these factors indicates that only a minority of ChIP-seq peaks showed enhancer activity (Figure 2D and S3C), with regions bound by OCT4 having the highest proportion of high activity enhancers. 30031062 chr8 66917733 66919733 SNHG6 Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6]. human High+Lowthroughput Long noncoding RNA SNHG6 regulates p21 expression via activation of the JNK pathway and regulation of EZH2 in gastric cancer cells 否 gastric cancer GC cell E_02_0517 QRT PCR, immunohistochemical staining, Western blot, rna-fish, statistical analysis Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6]. Immunohistochemical staining Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6]. qRT-PCR,Immunohistochemical staining,western blot,RNA-FISH,统计分析 SNHG6,EZH2,H19,XIST Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6].;Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6].;Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6].;Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. H19 and XIST, the first two non-coding RNAs (ncRNAs), are found to lack large open reading frames and the capability to produce identifiable protein products [4-6]. 30031040 chr10 88950934 88952934 FAS PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. Previously, PFASs, particularly PFOS and perfluorooctanoic acid (PFOA), were reported to promote adipogenesis in 3T3-L1 adipocytes with increased expression of adipogenic genes, including CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) (Watkins et al. 2015, Yamamoto et al. human High+Lowthroughput Perfluorobutanesulfonic acid (PFBS) potentiates adipogenesis of 3T3-L1 adipocytes 否 3T3‑L1 adipocytes E_02_0518 Q-PCR, MTT assay, immunoblotting, Western blot PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. Previously, PFASs, particularly PFOS and perfluorooctanoic acid (PFOA), were reported to promote adipogenesis in 3T3-L1 adipocytes with increased expression of adipogenic genes, including CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) (Watkins et al. 2015, Yamamoto et al. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. Previously, PFASs, particularly PFOS and perfluorooctanoic acid (PFOA), were reported to promote adipogenesis in 3T3-L1 adipocytes with increased expression of adipogenic genes, including CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) (Watkins et al. 2015, Yamamoto et al. Immunohistochemical staining PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. Previously, PFASs, particularly PFOS and perfluorooctanoic acid (PFOA), were reported to promote adipogenesis in 3T3-L1 adipocytes with increased expression of adipogenic genes, including CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) (Watkins et al. 2015, Yamamoto et al. q-PCR,MTT法,Immunoblotting,western blot FAS,FABP4 PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. Previously, PFASs, particularly PFOS and perfluorooctanoic acid (PFOA), were reported to promote adipogenesis in 3T3-L1 adipocytes with increased expression of adipogenic genes, including CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) (Watkins et al. 2015, Yamamoto et al.;PFBS treatments significantly increased the protein and mRNA levels of the master transcription factors in adipocyte differentiation; CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), along with acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), the key proteins in lipogenesis. Previously, PFASs, particularly PFOS and perfluorooctanoic acid (PFOA), were reported to promote adipogenesis in 3T3-L1 adipocytes with increased expression of adipogenic genes, including CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) (Watkins et al. 2015, Yamamoto et al. 30030400 chr7 148804570 148806570 EZH2 Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1. human High+Lowthroughput EZH2 Methyltransferase Activity Controls Pten Expression and mTOR Signaling during Fear Memory Reconsolidation 否 E_02_0519 ELISA, real-time PCR, Wesern blot, statistical analysis Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1. Immunohistochemical staining Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1. ELISA,real-time PCR,wesern blot,统计分析 EZH2,PTEN,PDPK1 Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1.;Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1.;Here, we found that in male rats retrieval of a contextual fear memory transiently increased Enhancer of Zeste Homolog 2 (EZH2) levels along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, which correlated with decreased levels of phosphatase and tensin homolog (PTEN), a potent inhibitor of AKT mTOR-dependent signaling in the hippocampus. Further experiments found increased H3K27me3 levels and DNA methylation across the Pten promoter and coding regions, indicating transcriptional silencing of the Pten gene. In this pathway, PI3K phosphorylates phosphatidylinositol(3,4,5)-trisphosphate (PIP3), which regulates the phosphorylation of AKT through PDPK1. 30029004 chr1 50020990 50022990 ELAVL4 Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008). human High+Lowthroughput HuD Is a Neural Translation Enhancer Acting on mTORC1-Responsive Genes and Counteracted by the Y3 Small Non-coding RNA 否 Neuroblastoma, amyotrophic lateral sclerosis (ALS) NSC-34 cell E_02_0520 RT qPCR, immunofluorescence staining, RNA SEQ, pol SEQ, northern, Western blot, statistical analysis Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008). Immunohistochemical staining Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008). RT-qPCR,免疫荧光染色,RNA-Seq,POL-Seq,Northern,western blot,统计分析 ELAVL4,ELAVL2,ELAVL1 Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008).;Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008).;Object name is fx1.jpg Go to: Introduction The intensively studied RNA-binding protein (RBP) human antigen D (HuD)/embryonic lethal, abnormal vision like 4 (ELAVL4) is predominantly expressed in differentiated neurons, as are the other neuronal members (nELAV) of the ELAV family, HuB (ELAVL2) and HuC (ELAVL3). In contrast, HuR (ELAVL1) is ubiquitously expressed (Pascale et al., 2008). 30026272 chr9 32544664 32546664 Ets1 Approach and Results We screened various combinations of transcription factors, including Myocd, Mef2C, Mef2B, Mkl1, Gata4, Gata5, Gata6, Ets1, and their corresponding carboxyterminal fusions to the transactivation domain of MyoD indicated by *-, for their effects on reprogramming mouse embryonic fibroblasts (MEFs) and human adult dermal fibroblasts (hFBs) to the smooth muscle cell fate as determined by the expression of specific markers. mouse High+Lowthroughput Direct Reprogramming of Fibroblasts Into Smooth Muscle-Like Cells With Defined Transcription Factors-Brief Report 否 inflammation smooth muscle cell E_02_0521 QRT PCR, immunofluorescence staining, statistical analysis Approach and Results We screened various combinations of transcription factors, including Myocd, Mef2C, Mef2B, Mkl1, Gata4, Gata5, Gata6, Ets1, and their corresponding carboxyterminal fusions to the transactivation domain of MyoD indicated by *-, for their effects on reprogramming mouse embryonic fibroblasts (MEFs) and human adult dermal fibroblasts (hFBs) to the smooth muscle cell fate as determined by the expression of specific markers. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Approach and Results We screened various combinations of transcription factors, including Myocd, Mef2C, Mef2B, Mkl1, Gata4, Gata5, Gata6, Ets1, and their corresponding carboxyterminal fusions to the transactivation domain of MyoD indicated by *-, for their effects on reprogramming mouse embryonic fibroblasts (MEFs) and human adult dermal fibroblasts (hFBs) to the smooth muscle cell fate as determined by the expression of specific markers. Immunohistochemical staining Approach and Results We screened various combinations of transcription factors, including Myocd, Mef2C, Mef2B, Mkl1, Gata4, Gata5, Gata6, Ets1, and their corresponding carboxyterminal fusions to the transactivation domain of MyoD indicated by *-, for their effects on reprogramming mouse embryonic fibroblasts (MEFs) and human adult dermal fibroblasts (hFBs) to the smooth muscle cell fate as determined by the expression of specific markers. qRT-PCR,免疫荧光染色,统计分析 Ets1,Gata4 Approach and Results We screened various combinations of transcription factors, including Myocd, Mef2C, Mef2B, Mkl1, Gata4, Gata5, Gata6, Ets1, and their corresponding carboxyterminal fusions to the transactivation domain of MyoD indicated by *-, for their effects on reprogramming mouse embryonic fibroblasts (MEFs) and human adult dermal fibroblasts (hFBs) to the smooth muscle cell fate as determined by the expression of specific markers.;Approach and Results We screened various combinations of transcription factors, including Myocd, Mef2C, Mef2B, Mkl1, Gata4, Gata5, Gata6, Ets1, and their corresponding carboxyterminal fusions to the transactivation domain of MyoD indicated by *-, for their effects on reprogramming mouse embryonic fibroblasts (MEFs) and human adult dermal fibroblasts (hFBs) to the smooth muscle cell fate as determined by the expression of specific markers. 30021904 chr4 26160604 26162604 RBPJ We demonstrate that EBNA2 can activate IRF4 and miR-155HG expression through specific upstream enhancers that are dependent on the Notch signaling transcription factor RBPJ, a known binding partner of EBNA2. human High+Lowthroughput Enhancer Control of MicroRNA miR-155 Expression in Epstein-Barr Virus-Infected B Cells 否 Malignancy B cell E_02_0522 SDS-PAGE and Western blotting,ChIP-QPCR,RT-QPCR,western blot We demonstrate that EBNA2 can activate IRF4 and miR-155HG expression through specific upstream enhancers that are dependent on the Notch signaling transcription factor RBPJ, a known binding partner of EBNA2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate that EBNA2 can activate IRF4 and miR-155HG expression through specific upstream enhancers that are dependent on the Notch signaling transcription factor RBPJ, a known binding partner of EBNA2. Immunohistochemical staining We demonstrate that EBNA2 can activate IRF4 and miR-155HG expression through specific upstream enhancers that are dependent on the Notch signaling transcription factor RBPJ, a known binding partner of EBNA2. SDS-PAGE and Western blotting,ChIP-QPCR,RT-QPCR,western blot RBPJ We demonstrate that EBNA2 can activate IRF4 and miR-155HG expression through specific upstream enhancers that are dependent on the Notch signaling transcription factor RBPJ, a known binding partner of EBNA2. 30021842 chr17 72118219 72120219 SOX9 SOX9 controls cell lineage fate and differentiation in major biological processes. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9. human High+Lowthroughput SOX9 is dispensable for the initiation of epigenetic remodeling and the activation of marker genes at the onset of chondrogenesis 否 Osteoarthritis chondroblast E_02_0523 RNA-seq,qRT-PCR,ChIP-seq SOX9 controls cell lineage fate and differentiation in major biological processes. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SOX9 controls cell lineage fate and differentiation in major biological processes. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9. Immunohistochemical staining SOX9 controls cell lineage fate and differentiation in major biological processes. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9. RNA-seq,qRT-PCR,ChIP-seq SOX9,Myh14 SOX9 controls cell lineage fate and differentiation in major biological processes. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9.;SOX9 controls cell lineage fate and differentiation in major biological processes. By profiling the whole transcriptome and the whole epigenome of wild-type and Sox9-deficient mouse embryo limb buds, we uncover multiple structural and regulatory genes, including Fam101a, Myh14, Sema3c and Sema3d, as specific markers of precartilaginous condensation, and we provide evidence of their direct transactivation by SOX9. 30018722 chr9 104777916 104779916 ABCA1 Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. human High+Lowthroughput Apolipoprotein B-100 peptide 210 antibody inhibits atherosclerosis by regulation of macrophages that phagocytize oxidized lipid 否 atherosclerosis macrophage E_02_0524 ELISA, Western blot, immunohistochemistry, flow cytometry, immunofluorescence staining, oil-red-O staining, statistical analysis Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Immunohistochemical staining Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. ELISA,Western blot,Immunohistochemistry,流式细胞术,免疫荧光染色,Oil-red-O staining,统计分析 ABCA1 Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. 30017589 chr13 30108722 30109111 GRHL2 Here, we show the transcription factor GRHL2 is necessary and sufficient to activate an epithelial subset of enhancers as naïve embryonic stem cells (ESCs) transition into formative epiblast-like cells (EpiLCs). human Low+High throughput GRHL2-Dependent Enhancer Switching Maintains a Pluripotent Stem Cell Transcriptional Subnetwork after Exit from Naive Pluripotency 否 -- stem cell E_02_0525 ChIP-seq Our findings were corroborated by H3K4me1 and H3K27ac ChIP-seq data from an alternative na?ve-to-formative differentiation system. As a control, we found little change in these marks at SMC1 sites common to both states. These results indicate that GRHL2 binding correlates with full enhancer activation, suggesting a role for GRHL2 not only in regulation of cohesin binding, but also in regulation of other crucial steps in enhancer activation.Together, these results suggest that our SMC1 ChIP-seq data reflect changing enhancer activity and that cohesin binding at enhancers is highly dynamic during the ESC to EpiLC transition. Enhancer CRISPR/Cas9 ChIP-seq,qRT-PCR 2300002E22Rik,5730453H04Rik,AA407887,AA407888,AW109828,DP,rul GRHL2 therefore control over a subset of the naive network via Enhancer switching to maintain expression of epithelial genes upon exit from naive pluripotency ChIP-seq Together,these results suggest that our SMC1 ChIP-seq data reflect changing Enhancer activity and that cohesin binding at Enhancers is highly dynamic during the ESC to EpiLC transition. 0610015A08Rik,BOM,Tcfcp2l3,clft3 ChIP-seq,ATAC-seq -- -- Dsp,Dsp,Dsp,Dsp Grhl2,Grhl2,Grhl2,Grhl2 We then assessed the effects of each Enhancer deletion on Dsp expression in ES cells and EpiLCs by qRT-PCR.Indeed, we found that deletion of one or both KLF4-bound enhancers led to a significant reduction in Dsp expression in ESCs but had no effect in EpiLCs(Figure 6B). Conversely, deletion of the GRHL2-bound enhancer resulted in significantly reduced Dsp expression in the EpiLC state but had no effect in ESCs (Figure 6B). We observed similar state-specific reductions in target gene expression with deletions of the KLF4-bound and GRHL2-bound enhancers at the Cdh1 and Jam1 loci (Figure 6C and D, S6A and B).;We then assessed the effects of each Enhancer deletion on Dsp expression in ES cells and EpiLCs by qRT-PCR.Indeed, we found that deletion of one or both KLF4-bound enhancers led to a significant reduction in Dsp expression in ESCs but had no effect in EpiLCs(Figure 6B). Conversely, deletion of the GRHL2-bound enhancer resulted in significantly reduced Dsp expression in the EpiLC state but had no effect in ESCs (Figure 6B). We observed similar state-specific reductions in target gene expression with deletions of the KLF4-bound and GRHL2-bound enhancers at the Cdh1 and Jam1 loci (Figure 6C and D, S6A and B).;We then assessed the effects of each Enhancer deletion on Dsp expression in ES cells and EpiLCs by qRT-PCR.Indeed, we found that deletion of one or both KLF4-bound enhancers led to a significant reduction in Dsp expression in ESCs but had no effect in EpiLCs(Figure 6B). Conversely, deletion of the GRHL2-bound enhancer resulted in significantly reduced Dsp expression in the EpiLC state but had no effect in ESCs (Figure 6B). We observed similar state-specific reductions in target gene expression with deletions of the KLF4-bound and GRHL2-bound enhancers at the Cdh1 and Jam1 loci (Figure 6C and D, S6A and B).;We then assessed the effects of each Enhancer deletion on Dsp expression in ES cells and EpiLCs by qRT-PCR.Indeed, we found that deletion of one or both KLF4-bound enhancers led to a significant reduction in Dsp expression in ESCs but had no effect in EpiLCs(Figure 6B). Conversely, deletion of the GRHL2-bound enhancer resulted in significantly reduced Dsp expression in the EpiLC state but had no effect in ESCs (Figure 6B). We observed similar state-specific reductions in target gene expression with deletions of the KLF4-bound and GRHL2-bound enhancers at the Cdh1 and Jam1 loci (Figure 6C and D, S6A and B). Given the strong association between GRHL2 binding and various events in enhancer activation, we asked whether GRHL2 binding is necessary for each of these events. To address this question, we assessed levels of each active enhancer mark in wildtype and GHRL2 KO EpiLCs by performing ATAC-seq and ChIP-seq for H3K4me1, H3K27ac, and SMC1. There was a strong reduction in all active enhancer marks (chromatin accessibility, H3K4me1, H3K27ac, and SMC1 levels) at GRHL2 sites in GRHL2 KO EpiLCs, suggesting a near complete block in enhancer activation in the absence of GRHL2. Together, these results indicate an absolute requirement for GRHL2 for enhancer activation specifically at its target sites.;Given the strong association between GRHL2 binding and various events in enhancer activation, we asked whether GRHL2 binding is necessary for each of these events. To address this question, we assessed levels of each active enhancer mark in wildtype and GHRL2 KO EpiLCs by performing ATAC-seq and ChIP-seq for H3K4me1, H3K27ac, and SMC1. There was a strong reduction in all active enhancer marks (chromatin accessibility, H3K4me1, H3K27ac, and SMC1 levels) at GRHL2 sites in GRHL2 KO EpiLCs, suggesting a near complete block in enhancer activation in the absence of GRHL2. Together, these results indicate an absolute requirement for GRHL2 for enhancer activation specifically at its target sites.;Given the strong association between GRHL2 binding and various events in enhancer activation, we asked whether GRHL2 binding is necessary for each of these events. To address this question, we assessed levels of each active enhancer mark in wildtype and GHRL2 KO EpiLCs by performing ATAC-seq and ChIP-seq for H3K4me1, H3K27ac, and SMC1. There was a strong reduction in all active enhancer marks (chromatin accessibility, H3K4me1, H3K27ac, and SMC1 levels) at GRHL2 sites in GRHL2 KO EpiLCs, suggesting a near complete block in enhancer activation in the absence of GRHL2. Together, these results indicate an absolute requirement for GRHL2 for enhancer activation specifically at its target sites.;Given the strong association between GRHL2 binding and various events in enhancer activation, we asked whether GRHL2 binding is necessary for each of these events. To address this question, we assessed levels of each active enhancer mark in wildtype and GHRL2 KO EpiLCs by performing ATAC-seq and ChIP-seq for H3K4me1, H3K27ac, and SMC1. There was a strong reduction in all active enhancer marks (chromatin accessibility, H3K4me1, H3K27ac, and SMC1 levels) at GRHL2 sites in GRHL2 KO EpiLCs, suggesting a near complete block in enhancer activation in the absence of GRHL2. Together, these results indicate an absolute requirement for GRHL2 for enhancer activation specifically at its target sites. 30014220 chr16 69184468 69186468 SNTB2 The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. In vitro data suppose a function of the syntrophins in stabilizing ATP-binding cassette transporter A1 (ABCA1), a major regulator of serum cholesterol levels [8]. human adipose High+Lowthroughput The utrophin-beta 2 syntrophin complex regulates adipocyte lipid droplet size independent of adipogenesis 否 inflammation 3T3‑L1 adipocytes E_02_0526 Western blot, immunofluorescence staining, gene knockdown The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. In vitro data suppose a function of the syntrophins in stabilizing ATP-binding cassette transporter A1 (ABCA1), a major regulator of serum cholesterol levels [8]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. In vitro data suppose a function of the syntrophins in stabilizing ATP-binding cassette transporter A1 (ABCA1), a major regulator of serum cholesterol levels [8]. Immunohistochemical staining The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. In vitro data suppose a function of the syntrophins in stabilizing ATP-binding cassette transporter A1 (ABCA1), a major regulator of serum cholesterol levels [8]. western blot,免疫荧光染色,基因敲降 SNTB2,ABCA1 The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. In vitro data suppose a function of the syntrophins in stabilizing ATP-binding cassette transporter A1 (ABCA1), a major regulator of serum cholesterol levels [8].;The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. In vitro data suppose a function of the syntrophins in stabilizing ATP-binding cassette transporter A1 (ABCA1), a major regulator of serum cholesterol levels [8]. 30012865 chr11 5279732 5280272 USF1 This site is occupied by transcription factors USF1, USF2, EGR1, MafK, and NF-E2 in the human erythroleukemia cell line K562 and exhibits histone modifications typical for enhancers. human Low+High throughput Identification of a Novel Enhancer/Chromatin Opening Element Associated with High-Level γ-Globin Gene Expression 是 Erythrocytic Leukemia erythrocyte E_02_0527 ChIP-seq We generated a synthetic zinc finger DNA-binding domain (ZF) targeting the HBG-4kb HS. The HBG-4kb ZF interacted with the target site in vitro and in the context of cells with high affinity and specificity. Enhancer -- PCR HBG-T1,TNCY the HBG-4kb HS site is important for fetal globin production and suggest that it may act by opening chromatin in a directional manner. CRISPR/Cas9 Expression of the adult β-globin, the embryonic -globin, and the GATA1 genes was not affected by the HBG-4kb ZF. Delivery of the Control ZF did not cause any change in expression of the γ-globin, β-globin, -globin, or GATA1 genes. FCHL,FCHL1,HYPLIP1,MLTF,MLTFI,UEF,bHLHb11,FIP,bHLHb12,AT225,G0S30,KROX-24,NGFI-A,TIS8,ZIF-268,ZNF225,NFE2U,P18,NF-E2,p45 ChIP -- -- HBG2,HBG2,HBG2 USF1,USF2,EGR1,MAFK,NFE2,USF1,USF2,EGR1,MAFK,NFE2,USF1,USF2,EGR1,MAFK,NFE2 The regions that we analyzed were the HBG-4kb HS,a 327 region located 4 kb upstream (HBG-8kb) or 1 and 2 kb downstream(HBG-3kb and HBG-2kb) of 328 the HBG-4kb HS,the Gγ-(HBG2) and Aγ-(HBG1) globin gene promoter regions.;The regions that we analyzed were the HBG-4kb HS,a 327 region located 4 kb upstream (HBG-8kb) or 1 and 2 kb downstream(HBG-3kb and HBG-2kb) of 328 the HBG-4kb HS,the Gγ-(HBG2) and Aγ-(HBG1) globin gene promoter regions.;The regions that we analyzed were the HBG-4kb HS,a 327 region located 4 kb upstream (HBG-8kb) or 1 and 2 kb downstream(HBG-3kb and HBG-2kb) of 328 the HBG-4kb HS,the Gγ-(HBG2) and Aγ-(HBG1) globin gene promoter regions. Reduced binding of transcription factors with the HBG-4kb HS in K562 cells expressing the HBG-4kb ZF. K562 cells (Untreated) or K562 cells exposed to 500 nM HBG-4kb ZF for 12 h were subjected to ChIP using antibodies specific for EGR1, USF1, USF2, NF-E2 (p45), MafK, or the negative control, IgG.;Reduced binding of transcription factors with the HBG-4kb HS in K562 cells expressing the HBG-4kb ZF. K562 cells (Untreated) or K562 cells exposed to 500 nM HBG-4kb ZF for 12 h were subjected to ChIP using antibodies specific for EGR1, USF1, USF2, NF-E2 (p45), MafK, or the negative control, IgG.;Reduced binding of transcription factors with the HBG-4kb HS in K562 cells expressing the HBG-4kb ZF. K562 cells (Untreated) or K562 cells exposed to 500 nM HBG-4kb ZF for 12 h were subjected to ChIP using antibodies specific for EGR1, USF1, USF2, NF-E2 (p45), MafK, or the negative control, IgG. 30012153 chr7 96478877 96480877 SEM1 Some other endogenous amyloid aggregates that increase HIV-1 infectivity, including the PAP N-proximal fragment (PAP85 120) and semenogelins (SEM1 and SEM2), have been identified in human semen [7, 8], which may explain the discrepancy between the low infectiousness of HIV in vitro and its observed efficient sexual transmission. human High+Lowthroughput Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity 否 HIV TZM-b1 cell E_02_0528 MTT assay, WB assay, SPR analysis, flow cytometry, statistical analysis, immunofluorescence staining Some other endogenous amyloid aggregates that increase HIV-1 infectivity, including the PAP N-proximal fragment (PAP85 120) and semenogelins (SEM1 and SEM2), have been identified in human semen [7, 8], which may explain the discrepancy between the low infectiousness of HIV in vitro and its observed efficient sexual transmission. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Some other endogenous amyloid aggregates that increase HIV-1 infectivity, including the PAP N-proximal fragment (PAP85 120) and semenogelins (SEM1 and SEM2), have been identified in human semen [7, 8], which may explain the discrepancy between the low infectiousness of HIV in vitro and its observed efficient sexual transmission. Immunohistochemical staining Some other endogenous amyloid aggregates that increase HIV-1 infectivity, including the PAP N-proximal fragment (PAP85 120) and semenogelins (SEM1 and SEM2), have been identified in human semen [7, 8], which may explain the discrepancy between the low infectiousness of HIV in vitro and its observed efficient sexual transmission. MTT法,WB assay,,SPR analysis,流式细胞术,统计分析,免疫荧光染色 SEM1 Some other endogenous amyloid aggregates that increase HIV-1 infectivity, including the PAP N-proximal fragment (PAP85 120) and semenogelins (SEM1 and SEM2), have been identified in human semen [7, 8], which may explain the discrepancy between the low infectiousness of HIV in vitro and its observed efficient sexual transmission. 30010625 chr13 27917694 27919694 PDX1 BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. human Tumor High+Lowthroughput The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis 是 Pancreatic ductal adenocarcinoma (PDA) acinar cell E_02_0529 Immunohistochemistry,ChIP-seq,RT-PCR,ChIP qPCR BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. Immunohistochemical staining BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. Immunohistochemistry,ChIP-seq,RT-PCR,ChIP qPCR PDX1,SOX9 BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. ;BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. 30008319 chr4 129406952 129408952 Hdac1 The complex combines two enzymatic activities in the form of class I lysine deacetylation, encoded by the Hdac1 and 2 proteins, with the Swi/Snf-type ATPase and nucleosome remodeling of Chd4. mouse High+Lowthroughput The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression 否 E_02_0530 Chip SEQ, RNA SEQ, mnase SEQ, mnase qPCR, statistical analysis, Western blot The complex combines two enzymatic activities in the form of class I lysine deacetylation, encoded by the Hdac1 and 2 proteins, with the Swi/Snf-type ATPase and nucleosome remodeling of Chd4. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The complex combines two enzymatic activities in the form of class I lysine deacetylation, encoded by the Hdac1 and 2 proteins, with the Swi/Snf-type ATPase and nucleosome remodeling of Chd4. Immunohistochemical staining The complex combines two enzymatic activities in the form of class I lysine deacetylation, encoded by the Hdac1 and 2 proteins, with the Swi/Snf-type ATPase and nucleosome remodeling of Chd4. ChIP-seq,RNA-seq,MNase-seq,MNase qPCR,统计分析,western blot Hdac1 The complex combines two enzymatic activities in the form of class I lysine deacetylation, encoded by the Hdac1 and 2 proteins, with the Swi/Snf-type ATPase and nucleosome remodeling of Chd4. 30008316 chr1 160536893 160537651 INTS13 The control of cell fate is an epigenetic process initiated by transcription factors (TFs) that recognize DNA motifs and recruit activator complexes and transcriptional machineries to chromatin. Here we show that INTS13 functions as an independent sub-module and targets enhancers through Early Growth Response (EGR1/2) TFs and their co-factor NAB2. Independent depletion of INTS13, EGR1 or NAB2 impairs monocytic differentiation of cell lines and primary human progenitors. human Low+High throughput Targeted Enhancer Activation by a Subunit of the Integrator Complex 否 -- HL-60 E_02_0531 ChIP-seq,ChIP-qPCR Notably, INTS11-gained regions were largely enriched for proximal promoters(62.2%), mirroring the known RNAPII-associated activity of the complex, and displayed robust binding of INTS13 as well. Conversely, INTS13-gained regions were largely found distal from the TSS of protein-coding genes (82.5%) and only partially overlapped with INTS11. Enhancer CRISPR/Cas9,3C qRT-PCR LY9B,SLAMF5,hCD84,mCD84 -- -- -- ASUN,C12orf11,GCT1,Mat89Bb,NET48,SPATA30,AT225,G0S30,KROX-24,NGFI-A,TIS8,ZIF-268,ZNF225,MADER Immunoprecipitation,Colony-forming Unit (CFU) Assay -- -- CD84,CD84,CD84 INTS13,EGR1,NAB2,INTS13,EGR1,NAB2,INTS13,EGR1,NAB2 We performed chromosome conformation capture (3C) on the enhancer of CSF1R to infer the consequences of INTS13 depletion on genome architecture. During differentiation of HL-60 cells, we detected a robust interaction between the intronic enhancer of CSF1R and the proximal promoter, as compared to other regions within the CSF1R gene or with the promoter of neighboring genes.;We performed chromosome conformation capture (3C) on the enhancer of CSF1R to infer the consequences of INTS13 depletion on genome architecture. During differentiation of HL-60 cells, we detected a robust interaction between the intronic enhancer of CSF1R and the proximal promoter, as compared to other regions within the CSF1R gene or with the promoter of neighboring genes.;We performed chromosome conformation capture (3C) on the enhancer of CSF1R to infer the consequences of INTS13 depletion on genome architecture. During differentiation of HL-60 cells, we detected a robust interaction between the intronic enhancer of CSF1R and the proximal promoter, as compared to other regions within the CSF1R gene or with the promoter of neighboring genes. Immunoprecipitation of INTS13 in undifferentiated (CTRL) and differentiated (PMA) HL-60 cells confirms the interaction between INTS13 and NAB2 after PMA treatment.Colony-forming unit (CFU) assay of cord blood derived CD34+ cells infected with shRNAs against NAB2 and EGR1 shows that the number of monocytic/macrophagic colonies is significantly reduced in both NAB2- and EGR1-depleted cells when compared to control.;Immunoprecipitation of INTS13 in undifferentiated (CTRL) and differentiated (PMA) HL-60 cells confirms the interaction between INTS13 and NAB2 after PMA treatment.Colony-forming unit (CFU) assay of cord blood derived CD34+ cells infected with shRNAs against NAB2 and EGR1 shows that the number of monocytic/macrophagic colonies is significantly reduced in both NAB2- and EGR1-depleted cells when compared to control.;Immunoprecipitation of INTS13 in undifferentiated (CTRL) and differentiated (PMA) HL-60 cells confirms the interaction between INTS13 and NAB2 after PMA treatment.Colony-forming unit (CFU) assay of cord blood derived CD34+ cells infected with shRNAs against NAB2 and EGR1 shows that the number of monocytic/macrophagic colonies is significantly reduced in both NAB2- and EGR1-depleted cells when compared to control. 30006306 chr7 148804160 148806160 EZH2 The gene and protein expression of polycomb repressor13 proteins B cell specific moloney murine leukemia virus integration site 1 (BMI-1) and14 enhancer of zeste homolog 2 (EZH2) was significantly over expressed with enhanced15 trimethylation of H3K27 and ubiquitination of H2AK119. human High+Lowthroughput Aflatoxin B(1) induced multiple epigenetic modulators in human epithelial cell lines 否 leukemia HaCaT cell E_02_0532 MTT assay, quantitative real-time polymerase chain reaction, Western blot, and statistical analysis The gene and protein expression of polycomb repressor13 proteins B cell specific moloney murine leukemia virus integration site 1 (BMI-1) and14 enhancer of zeste homolog 2 (EZH2) was significantly over expressed with enhanced15 trimethylation of H3K27 and ubiquitination of H2AK119. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The gene and protein expression of polycomb repressor13 proteins B cell specific moloney murine leukemia virus integration site 1 (BMI-1) and14 enhancer of zeste homolog 2 (EZH2) was significantly over expressed with enhanced15 trimethylation of H3K27 and ubiquitination of H2AK119. Immunohistochemical staining The gene and protein expression of polycomb repressor13 proteins B cell specific moloney murine leukemia virus integration site 1 (BMI-1) and14 enhancer of zeste homolog 2 (EZH2) was significantly over expressed with enhanced15 trimethylation of H3K27 and ubiquitination of H2AK119. MTT法,quantitative real-time polymerase chain reaction,Western blot,统计分析 EZH2 The gene and protein expression of polycomb repressor13 proteins B cell specific moloney murine leukemia virus integration site 1 (BMI-1) and14 enhancer of zeste homolog 2 (EZH2) was significantly over expressed with enhanced15 trimethylation of H3K27 and ubiquitination of H2AK119. 30003124 chr12 25202764 25204764 KRAS Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. human High+Lowthroughput E47 Governs the MYC-CDKN1B/p27(KIP1)-RB Network to Growth Arrest PDA Cells Independent of CDKN2A/p16(INK4A) and Wild-Type p53 否 Pancreatic ductal adenocarcinoma (PDA) E_02_0533 RNA SEQ, cell cycle PCR array analysis, flow cytometry, statistical analysis Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. Immunohistochemical staining Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. RNA-Seq,Cell-Cycle PCR Array Analysis,流式细胞术,统计分析 KRAS,MYC,CDKN2A,SMAD4 Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. ;Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. ;Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. ;Background & Aims Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16INK4A, and SMAD4, drive progression of pancreatic ductal adenocarcinoma (PDA).Overexpression of MYC and deregulation of retinoblastoma (RB) further promote cell proliferation and make identifying a means to therapeutically alter cell-cycle control pathways in PDA a significant challenge. 30002127 chr19 33297216 33299216 CEBPA Lack of, aberrant or suboptimal C/EBPα activity can result from genomic mutations in the CEBPA gene,8 transcriptional suppression originating from promoter hypermethylation, or functional inactivation by phosphorylation. human High+Lowthroughput Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells 否 Acute myeloid leukemia HL-60 E_02_0534 Western blot, real time PCR, statistical analysis Lack of, aberrant or suboptimal C/EBPα activity can result from genomic mutations in the CEBPA gene,8 transcriptional suppression originating from promoter hypermethylation, or functional inactivation by phosphorylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Lack of, aberrant or suboptimal C/EBPα activity can result from genomic mutations in the CEBPA gene,8 transcriptional suppression originating from promoter hypermethylation, or functional inactivation by phosphorylation. Immunohistochemical staining Lack of, aberrant or suboptimal C/EBPα activity can result from genomic mutations in the CEBPA gene,8 transcriptional suppression originating from promoter hypermethylation, or functional inactivation by phosphorylation. Western blot,Real-Time PCR,统计分析 CEBPA Lack of, aberrant or suboptimal C/EBPα activity can result from genomic mutations in the CEBPA gene,8 transcriptional suppression originating from promoter hypermethylation, or functional inactivation by phosphorylation. 30002061 chr21 43049901 43051901 CBS Since laminar flow-induced CSE suppression is lost in areas of disturbed flow, we wanted to know whether this led to the elevation of H2S and its metabolites. human High+Lowthroughput Cystathionine γ-Lyase Modulates Flow-Dependent Vascular Remodeling 否 atherosclerosis endothelial cell E_02_0535 Immunoblotting, QRT PCR, immunocytochemistry, statistical analysis Since laminar flow-induced CSE suppression is lost in areas of disturbed flow, we wanted to know whether this led to the elevation of H2S and its metabolites. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Since laminar flow-induced CSE suppression is lost in areas of disturbed flow, we wanted to know whether this led to the elevation of H2S and its metabolites. Immunohistochemical staining Since laminar flow-induced CSE suppression is lost in areas of disturbed flow, we wanted to know whether this led to the elevation of H2S and its metabolites. Immunoblotting,qRT-PCR,Immunocytochemistry,统计分析 CBS Since laminar flow-induced CSE suppression is lost in areas of disturbed flow, we wanted to know whether this led to the elevation of H2S and its metabolites. 29995890 chr15 90963074 90965074 PRC1 Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability. human High+Lowthroughput Cyclin G and the Polycomb Repressive complexes PRC1 and PR-DUB cooperate for developmental stability 否 Mesothelioma cell E_02_0536 RNA-seq,RT-qPCR,ChIP-seq,ChIP-qPCR Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability. Immunohistochemical staining Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability. RNA-seq,RT-qPCR,ChIP-seq,ChIP-qPCR PRC1 Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability. 29992973 chr13 99979122 99981122 ZIC2 ZIC2 mutation is known to cause holoprosencephaly (HPE). human High+Lowthroughput A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity 是 rs13482392 Holoprosencephaly (HPE), congenital heart E_02_0537 Microarray analysis,qPCR,In situ hybridisation,Chip-Seq,EMSA assays ZIC2 mutation is known to cause holoprosencephaly (HPE). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ZIC2 mutation is known to cause holoprosencephaly (HPE). Immunohistochemical staining ZIC2 mutation is known to cause holoprosencephaly (HPE). Microarray analysis,qPCR,In situ hybridisation,Chip-Seq,EMSA assays ZIC2 ZIC2 mutation is known to cause holoprosencephaly (HPE). 29985393 chr1 116751815 116753815 CD2 Go to: Results Characteristics of thymic iNKT cell subsets We analyzed thymic iNKT cells from BALB/c mice in which the human CD2 gene was knocked-in into the IL-4 locus (KN2), thereby allowing for the identification by flow cytometry of IL-4-secreting iNKT2 cells directly ex vivo. Development of iNKT cells diverges from that of conventional T cells primarily at the double-positive CD4+ CD8+ (DP) stage and requires TCR recognition of CD1d on DP cells, involving homotypic interactions across a DP DP synapse where second signals are initiated by the engagement of homophilic receptors of the signaling lymphocytic-activation molecule (SLAM) family, Slamf1 (SLAM) and Slamf6 (Ly108). human High+Lowthroughput TCR signal strength controls thymic differentiation of iNKT cell subsets 否 E_02_0538 RNA SEQ, RNA SEQ, statistical analysis, flow cytometry Go to: Results Characteristics of thymic iNKT cell subsets We analyzed thymic iNKT cells from BALB/c mice in which the human CD2 gene was knocked-in into the IL-4 locus (KN2), thereby allowing for the identification by flow cytometry of IL-4-secreting iNKT2 cells directly ex vivo. Development of iNKT cells diverges from that of conventional T cells primarily at the double-positive CD4+ CD8+ (DP) stage and requires TCR recognition of CD1d on DP cells, involving homotypic interactions across a DP DP synapse where second signals are initiated by the engagement of homophilic receptors of the signaling lymphocytic-activation molecule (SLAM) family, Slamf1 (SLAM) and Slamf6 (Ly108). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Go to: Results Characteristics of thymic iNKT cell subsets We analyzed thymic iNKT cells from BALB/c mice in which the human CD2 gene was knocked-in into the IL-4 locus (KN2), thereby allowing for the identification by flow cytometry of IL-4-secreting iNKT2 cells directly ex vivo. Development of iNKT cells diverges from that of conventional T cells primarily at the double-positive CD4+ CD8+ (DP) stage and requires TCR recognition of CD1d on DP cells, involving homotypic interactions across a DP DP synapse where second signals are initiated by the engagement of homophilic receptors of the signaling lymphocytic-activation molecule (SLAM) family, Slamf1 (SLAM) and Slamf6 (Ly108). Immunohistochemical staining Go to: Results Characteristics of thymic iNKT cell subsets We analyzed thymic iNKT cells from BALB/c mice in which the human CD2 gene was knocked-in into the IL-4 locus (KN2), thereby allowing for the identification by flow cytometry of IL-4-secreting iNKT2 cells directly ex vivo. Development of iNKT cells diverges from that of conventional T cells primarily at the double-positive CD4+ CD8+ (DP) stage and requires TCR recognition of CD1d on DP cells, involving homotypic interactions across a DP DP synapse where second signals are initiated by the engagement of homophilic receptors of the signaling lymphocytic-activation molecule (SLAM) family, Slamf1 (SLAM) and Slamf6 (Ly108). RNA-Seq,RNA-Seq,统计分析,流式细胞术 CD2 Go to: Results Characteristics of thymic iNKT cell subsets We analyzed thymic iNKT cells from BALB/c mice in which the human CD2 gene was knocked-in into the IL-4 locus (KN2), thereby allowing for the identification by flow cytometry of IL-4-secreting iNKT2 cells directly ex vivo. Development of iNKT cells diverges from that of conventional T cells primarily at the double-positive CD4+ CD8+ (DP) stage and requires TCR recognition of CD1d on DP cells, involving homotypic interactions across a DP DP synapse where second signals are initiated by the engagement of homophilic receptors of the signaling lymphocytic-activation molecule (SLAM) family, Slamf1 (SLAM) and Slamf6 (Ly108). 29979962 chr7 46371356 46373481 CTCF Tridimensional enhancer-promoter interactions are mediated by DNA, RNA, and protein components, including transcription factors and chromatin-binding CTCF and Cohesin complexes (Bonev and Cavalli, 2016). human Low throughput A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription In trans 否 -- neural progenitor cell E_02_0539 ChIRP To directly evaluate whether the DRReRNA 2Kb transcript could undergo splicing, we cloned it into the splicing reporter plasmid RHCglo.The resulting plasmid (RHCglo-DRR) or the parental vector were transiently transfected in human embryonic kidney 293 cells, in C2C12 MB or C2C12 cells induced to differentiate. RNA recovered from RHCglo-DRR-transfected cells and amplified with vector-specific primers gave rise to a single band of ~1.5Kb (Figure S1B,C), the same length observed for endogenous DRReRNA. Enhancer -- Western blot,RT-qPCR,ChIP AI503393,MYF3,MyoD,?Myod-1,bHLHc1 DRR eRNA Promotes Cohesin Recruitment and Maintenance at the Myogenin Locus qRT-PCR A non-coding RNA transcribed from an Enhancer region on mouse chromosome 7 (eRNA) recruits cohesin to regulate transcription of the Myogenin gene located on chromosome 1. -- -- -- -- Myod1 -- DRReRNA influences transcription of Myogenin in trans without significantly affecting that of MyoD in cis;This analysis revealed that the top two DRReRNA-enriched ChIRP regions were observed at Myogenin and DRR, whereas the MyoD gene located 5 kb downstream of DRR was devoid of DRReRNA binding. -- 29976669 chr6 170552062 170554062 TBP Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. human High+Lowthroughput Adenovirus E1A Activation Domain Regulates H3 Acetylation Affecting Varied Steps in Transcription at Different Viral Promoters 否 E_02_0540 qRT-PCR,ChIP-seq Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. Immunohistochemical staining Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. qRT-PCR,ChIP-seq TBP Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. 29973940 chr12 54359352 54361352 GPR84 GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. human High+Lowthroughput Activation of the Immune-Metabolic Receptor GPR84 Enhances Inflammation and Phagocytosis in Macrophages 否 diabetes macrophage E_02_0541 FACS, Western blot, immunofluorescence staining, chemotaxis assay GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. Immunohistochemical staining GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. FACS,western blot,免疫荧光染色,Chemotaxis Assay GPR84 GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. 29973282 chr12 78861267 78863267 SYT1 The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). The synaptic plasticity related proteins BDNF and SYT1 can not only promote neuronal regeneration but also regulate synaptic plasticity, thereby affecting the learning and memory functions of the brain. human High+Lowthroughput Possible mechanism of Vitis vinifera L. flavones on neurotransmitters, synaptic transmission and related learning and memory in Alzheimer model rats 否 Alzheimer's disease (AD) E_02_0542 Chat, ache assay, immunohistochemistry staining, Western blot, real time quantitative PCR, statistical analysis The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). The synaptic plasticity related proteins BDNF and SYT1 can not only promote neuronal regeneration but also regulate synaptic plasticity, thereby affecting the learning and memory functions of the brain. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). The synaptic plasticity related proteins BDNF and SYT1 can not only promote neuronal regeneration but also regulate synaptic plasticity, thereby affecting the learning and memory functions of the brain. Immunohistochemical staining The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). The synaptic plasticity related proteins BDNF and SYT1 can not only promote neuronal regeneration but also regulate synaptic plasticity, thereby affecting the learning and memory functions of the brain. ChAT、AChE检测,Immunohistochemistry staining,Western blot,Real-time quantitative PCR,统计分析 SYT1,BDNF The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). The synaptic plasticity related proteins BDNF and SYT1 can not only promote neuronal regeneration but also regulate synaptic plasticity, thereby affecting the learning and memory functions of the brain.;The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). The synaptic plasticity related proteins BDNF and SYT1 can not only promote neuronal regeneration but also regulate synaptic plasticity, thereby affecting the learning and memory functions of the brain. 29967281 chr17 85527960 85530660 Six3 Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. mouse Low+High throughput SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression 否 -- E_02_0543 Luciferase Reporter Assay,ChIP-seq We found an SP9 ChIP-Seq peak at the Six3 promoter region (?5 to +411 of the TSS) (Fig. 9C), and several additional peaks upstream of the Six3 gene (regions 1, 2 and 3) (Fig. 9C);Thus, these noncoding domains are strong candidates for the Six3 promoter and three Six3 enhancers. Enhancer -- ChIP-seq,Luciferase Reporter Assay E130112M24Rika,Six3alpha,Six3b,Six3beta,?Six3 -- -- -- E130112M24Rika，Six3alpha，Six3b，Six3beta RNA-seq,ChIP-seq -- -- Six3,Six3,Six3,Six3,Six3 Six3,Six3,Six3,Six3,Six3 Together,the results of ChIP-seq and Dual-Luciferase assay provide evidence that SP9 promotes Six3 expression in the LGE SVZ through its direct binding to the promoter and possibly through binding to regulatory elements within the Six3 locus.;Together,the results of ChIP-seq and Dual-Luciferase assay provide evidence that SP9 promotes Six3 expression in the LGE SVZ through its direct binding to the promoter and possibly through binding to regulatory elements within the Six3 locus.;Together,the results of ChIP-seq and Dual-Luciferase assay provide evidence that SP9 promotes Six3 expression in the LGE SVZ through its direct binding to the promoter and possibly through binding to regulatory elements within the Six3 locus.;Together,the results of ChIP-seq and Dual-Luciferase assay provide evidence that SP9 promotes Six3 expression in the LGE SVZ through its direct binding to the promoter and possibly through binding to regulatory elements within the Six3 locus.;Together,the results of ChIP-seq and Dual-Luciferase assay provide evidence that SP9 promotes Six3 expression in the LGE SVZ through its direct binding to the promoter and possibly through binding to regulatory elements within the Six3 locus. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants.This implies that there are additional mechanisms that regulate the generation of D2 MSNs in Sp9-KO mice, one of which was suggested by the LGE RNA-Seq analysis. We identified that expression of the TF Six3 was decreased ?5-fold in E16.5 Sp8/9-DCKO mice compared with control mice.;SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants.This implies that there are additional mechanisms that regulate the generation of D2 MSNs in Sp9-KO mice, one of which was suggested by the LGE RNA-Seq analysis. We identified that expression of the TF Six3 was decreased ?5-fold in E16.5 Sp8/9-DCKO mice compared with control mice.;SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants.This implies that there are additional mechanisms that regulate the generation of D2 MSNs in Sp9-KO mice, one of which was suggested by the LGE RNA-Seq analysis. We identified that expression of the TF Six3 was decreased ?5-fold in E16.5 Sp8/9-DCKO mice compared with control mice.;SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants.This implies that there are additional mechanisms that regulate the generation of D2 MSNs in Sp9-KO mice, one of which was suggested by the LGE RNA-Seq analysis. We identified that expression of the TF Six3 was decreased ?5-fold in E16.5 Sp8/9-DCKO mice compared with control mice.;SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants.This implies that there are additional mechanisms that regulate the generation of D2 MSNs in Sp9-KO mice, one of which was suggested by the LGE RNA-Seq analysis. We identified that expression of the TF Six3 was decreased ?5-fold in E16.5 Sp8/9-DCKO mice compared with control mice. 29966981 chr4 140556428 140558428 UCP1 Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes. human adipose High+Lowthroughput Heshouwu (Polygonum multiflorum Thunb.) ethanol extract suppresses pre-adipocytes differentiation in 3T3-L1 cells and adiposity in obese mice 否 Type 2 diabetes, obesity 3T3-L1 cell E_02_0544 Real time PCR, Western blot, and statistical analysis Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes. Immunohistochemical staining Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes. real-time PCR,Western blot,统计分析 UCP1,CPT2,DGAT2 Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes.;Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes.;Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes. 29966764 chrX 48519594 48521594 EBP In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. human adipose High+Lowthroughput Enhancer-driven transcriptional regulation is a potential key determinant for human visceral and subcutaneous adipocytes 否 Obesity fat cell E_02_0545 RT-qPCR,RNA-Seq,ChIP-Seq In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Immunohistochemical staining In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. RT-qPCR,RNA-Seq,ChIP-Seq EBP In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPAR implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. 29966306 chrX 48518772 48520772 EBP However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. human High+Lowthroughput Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines 否 Myeloid leukemia cells KG-1 cell E_02_0546 Real time PCR, Western blot, immunofluorescence staining, statistical analysis However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. Immunohistochemical staining However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. Real-Time PCR,Western Blot,免疫荧光染色,统计分析 EBP,VDR,CEBPD However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D.;However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D.;However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. 29958106 chr21 34785412 34787412 RUNX1 The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993). human High+Lowthroughput CBFβ-SMMHC Inhibition Triggers Apoptosis by Disrupting MYC Chromatin Dynamics in Acute Myeloid Leukemia 否 Myeloid leukemia cancer cell E_02_0547 Flow cytometry, quantitative RT-PCR, RNA SEQ, chip qPCR, chip SEQ, ATAC qPCR, ATAC SEQ, immunoblotting The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993). Immunohistochemical staining The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993). 流式细胞术,Quantitative RT-PCR,RNA-seq,ChIP qPCR,ChIP-seq,ATAC-qPCR,ATAC-seq,Immunoblotting RUNX1,MYC,CBFB,MYH11 The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993).;The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993).;The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993).;The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1.Here we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. The chromosome inversion inv(16)(p13;q22), found in 8% of acute myeloid leukemia (AML) cases, fuses the CBFB and MYH11 genes to produce the leukemic oncoprotein CBFβ-SMMHC (Liu et al., 1993). 29956731 chr7 148804007 148806007 EZH2 Therefore, an increased level of EZH2 is considered to indicate propensity for metastasis and poor outcome in patients with mammary tumors (21). human Breast cancer High+Lowthroughput Quercetin?3?methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways 否 mammary cancer Cancer stem cell E_02_0548 Western blot, statistical analysis, flow cytometry Therefore, an increased level of EZH2 is considered to indicate propensity for metastasis and poor outcome in patients with mammary tumors (21). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Therefore, an increased level of EZH2 is considered to indicate propensity for metastasis and poor outcome in patients with mammary tumors (21). Immunohistochemical staining Therefore, an increased level of EZH2 is considered to indicate propensity for metastasis and poor outcome in patients with mammary tumors (21). Western blot,统计分析,流式细胞术 EZH2 Therefore, an increased level of EZH2 is considered to indicate propensity for metastasis and poor outcome in patients with mammary tumors (21). 29953980 chr4 108044755 108046755 LEF1 Overexpression of LEF1 diminished repression of Wnt signalling and reduced proliferation activity in mangiferin-treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was independent of β-catenin but associated with WT1 protein. human High+Lowthroughput Repression of WT1-Mediated LEF1 Transcription by Mangiferin Governs β-Catenin-Independent Wnt Signalling Inactivation in Hepatocellular Carcinoma 否 Hepatocellular carcinoma (HCC) HCC cell E_02_0549 Real time quantitative PCR, chromatin immunoprecipitation (chip) assay, statistical analysis, immunofluorescence staining Overexpression of LEF1 diminished repression of Wnt signalling and reduced proliferation activity in mangiferin-treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was independent of β-catenin but associated with WT1 protein. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Overexpression of LEF1 diminished repression of Wnt signalling and reduced proliferation activity in mangiferin-treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was independent of β-catenin but associated with WT1 protein. Immunohistochemical staining Overexpression of LEF1 diminished repression of Wnt signalling and reduced proliferation activity in mangiferin-treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was independent of β-catenin but associated with WT1 protein. Real-time Quantitative PCR,Chromatin immunoprecipitation (ChIP) assay,统计分析,免疫荧光染色 LEF1,WT1 Overexpression of LEF1 diminished repression of Wnt signalling and reduced proliferation activity in mangiferin-treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was independent of β-catenin but associated with WT1 protein.;Overexpression of LEF1 diminished repression of Wnt signalling and reduced proliferation activity in mangiferin-treated HCC cells. The mangiferin-mediated down-regulation of LEF1 was independent of β-catenin but associated with WT1 protein. 29951200 chr2 26345102 26347102 Notch1 Background Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes. mouse High+Lowthroughput NICD-mediated notch transduction regulates the different fate of chicken primordial germ cells and spermatogonial stem cells 否 germ stem cell E_02_0550 Western blot, CO IP, QRT PCR, indirect immunofluorescence, statistical analysis Background Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Background Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes. Immunohistochemical staining Background Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes. Western blot,Co-IP,qRT-PCR,Indirect immunofluorescence,统计分析 Notch1,TLE4 Background Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes.;Background Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes. 35121887 chr6 145159621 145161621 Kras Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. mouse High+Lowthroughput Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer 不相关 pancreatic cancer progenitor cell E_02_0551 Small-scale RNA-seq, scRNA-seq ，small-scale ATAC-seq,Chromatin enrichment for proteomics.Immunoblotting, immunofluorescence and IHC. Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Immunohistochemical staining Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Small-scale RNA-seq, scRNA-seq ，small-scale ATAC-seq,Chromatin enrichment for proteomics.Immunoblotting, immunofluorescence and IHC. Kras Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. 34291139 chr10 97764137 97766137 SFRP5 Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. human High+Lowthroughput SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling 不相关 Vitiligo melanocyte,B16 cell E_02_0552 Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Immunohistochemical staining Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. SFRP5 Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. 33746938 chr11 72099986 72101986 Med31 We first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. mouse High+Lowthroughput Differential Requirements for Mediator Complex Subunits in Drosophila melanogaster Host Defense Against Fungal and Bacterial Pathogens 不相关 bacterial infection macrophage E_02_0553 Western blot We first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. Immunohistochemical staining We first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. 蛋白质印迹 Med31 We first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. 33604333 chr11 101448961 101450961 TRPC6 Transient receptor potential canonical 6 (TRPC6) channel is an important non-selective cation channel with a variety of physiological roles in the central nervous system. human Nervous High+Lowthroughput TRPC6 Attenuates Cortical Astrocytic Apoptosis and Inflammation in Cerebral Ischemic/Reperfusion Injury 不相关 Ischemic stroke cortical cell E_02_0554 TTC staining, flow cytometry, Western blot, immunofluorescence Transient receptor potential canonical 6 (TRPC6) channel is an important non-selective cation channel with a variety of physiological roles in the central nervous system. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transient receptor potential canonical 6 (TRPC6) channel is an important non-selective cation channel with a variety of physiological roles in the central nervous system. Immunohistochemical staining Transient receptor potential canonical 6 (TRPC6) channel is an important non-selective cation channel with a variety of physiological roles in the central nervous system. TTC 染色，流式细胞术，蛋白质印迹，免疫荧光 TRPC6 Transient receptor potential canonical 6 (TRPC6) channel is an important non-selective cation channel with a variety of physiological roles in the central nervous system. 33519497 chr6 41680863 41682863 TFEB We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. human Musculature High+Lowthroughput Activation of Tripartite Motif Containing 63 Expression by Transcription Factor EB and Transcription Factor Binding to Immunoglobulin Heavy Chain Enhancer 3 Is Regulated by Protein Kinase D and Class IIa Histone Deacetylases 不相关 Muscle wasting myocyte E_02_0555 Luciferase reporter assay, immunofluorescence, protein extraction and Western blot analysis, coimmunoprecipitation We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. Immunohistochemical staining We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. 荧光素酶报告检测，免疫荧光，蛋白质提取和蛋白质印迹分析，共免疫沉淀 TFEB We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. 33511127 chr7 148804442 148806442 EZH2 Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. human Musculature High+Lowthroughput RIP-Seq of EZH2 Identifies TCONS-00036665 as a Regulator of Myogenesis in Pigs 不相关 myoblast cell E_02_0556 Rip SEQ, lincrnaseq, Western blot, quantitative real-time PCR, immunofluorescence staining of cells Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. RIP-Seq，LincRNAseq，蛋白质印迹，定量实时荧光定量 PCR，细胞免疫荧光染色 EZH2 Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. 33537515 chr10 4558873 4560873 Esr1 The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. mouse connective High+Lowthroughput Assessment of Adipocyte Differentiation and Maturation-related Gene Expression in the Epididymal Fat of Estrogen Receptor α Knockout (ERαKO) Mouse during Postnatal Development Period 不相关 fat cell E_02_0557 Real time PCR The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. Immunohistochemical staining The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. 实时荧光定量 PCR Esr1 The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. 33553989 chr10 126881408 126883408 Cyp27b1 Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. mouse connective High+Lowthroughput Genomic Mechanisms Governing Mineral Homeostasis and the Regulation and Maintenance of Vitamin D Metabolism 不相关 osteocyte,nephrocyte E_02_0558 Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. Immunohistochemical staining Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. Cyp27b1 Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. 33488675 chr16 67559628 67561628 CTCF We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. human connective High+Lowthroughput Genome-Wide Histone Modifications and CTCF Enrichment Predict Gene Expression in Sheep Macrophages 不相关 Viruses such as small ruminant lentivirus and bacteria such as Coxiella bethesdensis alveolar macrophage E_02_0559 Chromatin immunoprecipitation and sequencing, chip SEQ data analysis We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. Immunohistochemical staining We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. 染色质免疫沉淀和测序，ChIP-Seq 数据分析 CTCF We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. 33453998 chr4 108044986 108046986 LEF1 We show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. human Epithelial High+Lowthroughput Hepatocyte nuclear factor 1β suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1 不相关 Cystic kidney disease kidney epithelial cell E_02_0560 Gene knockdown, luciferase reporter assay, genome wide chip SEQ analysis We show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Immunohistochemical staining We show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. 基因敲降,荧光素酶报告检测，全基因组ChIP-Seq分析 LEF1 We show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. 33454003 chr3 8726296 8728296 Hey1 Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. mouse Musculature High+Lowthroughput Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription 不相关 smooth muscle cell E_02_0561 Micro CT analysis, BAC lacZ Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. Immunohistochemical staining Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. Micro-CT分析， BAC-LacZ Hey1 Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. 33416105 chr7 148804533 148806533 EZH2 The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR-124-3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. human High+Lowthroughput Downregulation of hsa_circ_0026123 suppresses ovarian cancer cell metastasis and proliferation through the miR?124?3p/EZH2 signaling pathway 不相关 oophoroma OVA cell E_02_0562 Reverse transcription quantitative PCR (RT qPCR), Western blot analysis, fluorescence in situ hybridization (FISH) The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR-124-3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR-124-3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. Immunohistochemical staining The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR-124-3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. 逆转录定量 PCR （RT-qPCR），蛋白质印迹分析，荧光原位杂交 （FISH） EZH2 The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR-124-3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. 33388376 chr7 148804674 148806674 EZH2 The enhancer of zest homolog-2 (EZH2) has been demonstrated to participate in the development of brain injury. human High+Lowthroughput Knockdown EZH2 attenuates cerebral ischemia-reperfusion injury via regulating microRNA-30d-3p methylation and USP22 不相关 Cerebral ischemia-reperfusion Brain tissue cell E_02_0563 Methylation specific polymerase chain reaction (MSP). 2,3,5-Triphenyltetrazolium chloride (TTC) staining The enhancer of zest homolog-2 (EZH2) has been demonstrated to participate in the development of brain injury. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The enhancer of zest homolog-2 (EZH2) has been demonstrated to participate in the development of brain injury. Immunohistochemical staining The enhancer of zest homolog-2 (EZH2) has been demonstrated to participate in the development of brain injury. Methylation specific polymerase chain reaction (MSP). 2,3,5-Triphenyltetrazolium chloride (TTC) staining EZH2 The enhancer of zest homolog-2 (EZH2) has been demonstrated to participate in the development of brain injury. 33376128 chr19 39383229 39385229 PAF1 The RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) plays critical roles in modulating the release of paused RNAPII into productive elongation. human High+Lowthroughput The Paf1 complex positively regulates enhancer activity in mouse embryonic stem cells 不相关 cancer embryonic stem cell E_02_0564 CRISPR / cas9 assisted GFP labeling, chip SEQ, QRT PCR and RNA SEQ, immunostaining for Western blotting The RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) plays critical roles in modulating the release of paused RNAPII into productive elongation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) plays critical roles in modulating the release of paused RNAPII into productive elongation. Immunohistochemical staining The RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) plays critical roles in modulating the release of paused RNAPII into productive elongation. CRISPR/Cas9 辅助 GFP 标记，ChIP-seq，qRT-PCR 和 RNA-seq，免疫染色蛋白质印记 PAF1 The RNA polymerase II (RNAPII) associated factor 1 complex (Paf1C) plays critical roles in modulating the release of paused RNAPII into productive elongation. 33371364 chr4 73866599 73868599 CXCL1 DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. human connective High+Lowthroughput Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages 不相关 Lung inflammation alveolar macrophage E_02_0565 RNA extraction and quantitative real-time polymerase chain reaction (RT qPCR), cell viability and reactive oxygen species (ROS) measurement, Western blot analysis, Western blot analysis, DEP instillation DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. Immunohistochemical staining DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. RNA提取和定量实时聚合酶链反应（RT-qPCR），细胞活力和活性氧（ROS）测量，蛋白质印迹分析，蛋白质印迹分析，DEP灌输 CXCL1 DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. 33358566 chr7 148804311 148806311 EZH2 Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. human Epithelial High+Lowthroughput DZNep attenuates allergic airway inflammation in an ovalbumin-induced murine model 不相关 allergic airway inflammation goblet cell E_02_0566 Western blotting Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. Immunohistochemical staining Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. 蛋白质印记 EZH2 Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. 33340495 chr7 148804230 148806230 EZH2 In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). human High+Lowthroughput LncRNA embryonic stem cells expressed 1 (Lncenc1) is identified as a novel regulator in neuropathic pain by interacting with EZH2 and downregulating the expression of Bai1 in mouse microglia 不相关 Neuropathic pain embryonic stem cell E_02_0567 SUMC data analysis，SEER data analysis In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). Immunohistochemical staining In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). SUMC data analysis，SEER data analysis EZH2 In the mechanism exploration, we found that Lncenc1 could bind with the RNA binding protein (RBP) enhancer of zeste homologue 2 (EZH2), an identified contributor in microglial activation and neuropathic pain. Lncenc1 interacted with EZH2 and downregulated the expression of brain-specific angiogenesis inhibitor 1 (BAI1). 33334823 chr4 54096876 54098876 GSX2 Reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In Drosophila, the Gsx homolog, Ind, similarly represses or stimulates transcription in a site-dependent manner via an autoregulatory enhancer containing a combination of monomer and homodimer sites. human High+Lowthroughput Conserved Gsx2/Ind homeodomain monomer versus homodimer DNA binding defines regulatory outcomes in flies and mice 不相关 Neurogenic progenitor cell E_02_0568 Protein purification, electrophoretic mobility shift assay (EMSA), luciferase assay, chip qPCR, ribonucleic acid sequencing Reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In Drosophila, the Gsx homolog, Ind, similarly represses or stimulates transcription in a site-dependent manner via an autoregulatory enhancer containing a combination of monomer and homodimer sites. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In Drosophila, the Gsx homolog, Ind, similarly represses or stimulates transcription in a site-dependent manner via an autoregulatory enhancer containing a combination of monomer and homodimer sites. Immunohistochemical staining Reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In Drosophila, the Gsx homolog, Ind, similarly represses or stimulates transcription in a site-dependent manner via an autoregulatory enhancer containing a combination of monomer and homodimer sites. 蛋白质纯化，电泳迁移率转移检测 （EMSA），荧光素酶检测，ChIP-qPCR，核糖核酸测序 GSX2 Reporter assays showed that Gsx2 mediates opposing outcomes in a DNA binding site-dependent manner: Monomer Gsx2 binding represses transcription, whereas homodimer binding stimulates gene expression. In Drosophila, the Gsx homolog, Ind, similarly represses or stimulates transcription in a site-dependent manner via an autoregulatory enhancer containing a combination of monomer and homodimer sites. 33334620 chr1 156461041 156463041 MEF2D Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II). human Musculature High+Lowthroughput Protein kinase D participates in cardiomyocyte hypertrophy by regulating extracellular signal-regulated and myocyte enhancer factor 2D 不相关 hypertension cardiac muscle cell (sensu Arthopoda) E_02_0569 Western blot analysis, immunofluorescence staining, real-time quantitative polymerase chain reaction, small interfering RNA and its transfection Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II). Immunohistochemical staining Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II). 蛋白质印迹分析，免疫荧光染色，实时定量聚合酶链反应，小干扰RNA及其转染 MEF2D Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II). 33323375 chr5 150050709 150052709 CSF1R Were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). human High+Lowthroughput CNS macrophages differentially rely on an intronic Csf1r enhancer for their development 不相关 microglial cell E_02_0570 Immunostaining, ex vivo time-lapse imaging Were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). Immunohistochemical staining Were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). 免疫染色，离体延时成像 CSF1R Were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). 33322515 chrX 136144009 136146009 FHL1 The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. human High+Lowthroughput MiR-96-5p Induced by Palmitic Acid Suppresses the Myogenic Differentiation of C2C12 Myoblasts by Targeting FHL1 不相关 C2C12 cell E_02_0571 Transfection of oligonucleotides, RNA preparation and quantitative reverse transcription polymerase chain reaction (QRT PCR), dual luciferase reporter assay, Western blot analysis, immunofluorescence analysis, Western blot analysis The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Immunohistochemical staining The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Transfection of Oligonucleotides，RNA制备和定量逆转录-聚合酶链反应（qRT-PCR），双荧光素酶报告基因测定，免疫印迹分析，免疫荧光分析，免疫印迹分析 FHL1 The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. 33318687 chr10 86432735 86434735 WAPL We report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type specific binding sites. human High+Lowthroughput WAPL maintains a cohesin loading cycle to preserve cell-type-specific distal gene regulation 不相关 embryonic stem cell E_02_0572 Plasmid construction, gene targeting, Western blot, GFP quantification and cell cycle analysis, cell proliferation analysis, immunofluorescence staining, alkaline phosphatase staining, single cell colony formation assay, RT qPCR, chip SEQ riboprobes, TT SEQ, ATAC SEQ, chip SEQ analysis, ATAC SEQ analysis We report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type specific binding sites. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type specific binding sites. Immunohistochemical staining We report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type specific binding sites. 质粒构建，基因靶向，蛋白质印迹，GFP定量和细胞周期分析，细胞增殖分析，免疫荧光染色，碱性磷酸酶染色，单细胞集落形成测定，RT-qPCR，ChIP-seq核糖核酸序列，TT-seq，ATAC-seq，ChIP-seq 分析，ATAC-seq Analysis WAPL We report that the cohesin release factor WAPL creates a pool of free cohesin, in a process known as cohesin turnover, which reloads it to cell-type specific binding sites. 33287648 chr3 41191825 41193825 CTNNB1 Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. human High+Lowthroughput CTNNB1 Knockdown Inhibits Cell Proliferation and Aldosterone Secretion Through Inhibiting Wnt/β-Catenin Signaling in H295R Cells 不相关 Primary aldosteronism H295Rcell,cortical cell of adrenal gland E_02_0573 CTNNB1 Knockdown，Total RNA Extraction and qRT-PCR，Western Blot Analysis，Cell Viability Assays，Quantification of Aldosterone Using ELISA Kit Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Immunohistochemical staining Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. CTNNB1 Knockdown，Total RNA Extraction and qRT-PCR，Western Blot Analysis，Cell Viability Assays，Quantification of Aldosterone Using ELISA Kit CTNNB1 Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. 33264630 chr7 116521979 116523979 CAV1 CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. human lymphoid High+Lowthroughput Rare Variant Burden Analysis within Enhancers Identifies CAV1 as an ALS Risk Gene 不相关 Amyotrophic lateral sclerosis Lymphoblast E_02_0574 Immunoblotting, fluorescent quantitative PCR (RT-PCR), immunocytochemistry, live cell imaging CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. Immunohistochemical staining CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. 免疫印迹，荧光定量 PCR（RT-PCR），免疫细胞化学，活细胞成像 CAV1 CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. 33261193 chr7 117284424 117286424 CFTR In PKD, the decreased levels of intracellular calcium and the increased levels of intracellular cAMP lead to two pathophysiological events: (i) cyclic adenosine monophosphate (cAMP)-induced chloride secretion, in part driven by cystic fibrosis transmembrane conductance regulator (CFTR), and (ii) increased cell proliferation, at least in part mediated by mammalian target of rapamycin complex 1 (mTORC1). human Kidney High+Lowthroughput Novel Potential Application of Chitosan Oligosaccharide for Attenuation of Renal Cyst Growth in the Treatment of Polycystic Kidney Disease 不相关 Polycystic kidney disease renal tubular cell E_02_0575 Cell viability assay, immunoblotting, intracellular calcium measurement In PKD, the decreased levels of intracellular calcium and the increased levels of intracellular cAMP lead to two pathophysiological events: (i) cyclic adenosine monophosphate (cAMP)-induced chloride secretion, in part driven by cystic fibrosis transmembrane conductance regulator (CFTR), and (ii) increased cell proliferation, at least in part mediated by mammalian target of rapamycin complex 1 (mTORC1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In PKD, the decreased levels of intracellular calcium and the increased levels of intracellular cAMP lead to two pathophysiological events: (i) cyclic adenosine monophosphate (cAMP)-induced chloride secretion, in part driven by cystic fibrosis transmembrane conductance regulator (CFTR), and (ii) increased cell proliferation, at least in part mediated by mammalian target of rapamycin complex 1 (mTORC1). Immunohistochemical staining In PKD, the decreased levels of intracellular calcium and the increased levels of intracellular cAMP lead to two pathophysiological events: (i) cyclic adenosine monophosphate (cAMP)-induced chloride secretion, in part driven by cystic fibrosis transmembrane conductance regulator (CFTR), and (ii) increased cell proliferation, at least in part mediated by mammalian target of rapamycin complex 1 (mTORC1). 细胞活力测定，免疫印迹，细胞内钙测量 CFTR In PKD, the decreased levels of intracellular calcium and the increased levels of intracellular cAMP lead to two pathophysiological events: (i) cyclic adenosine monophosphate (cAMP)-induced chloride secretion, in part driven by cystic fibrosis transmembrane conductance regulator (CFTR), and (ii) increased cell proliferation, at least in part mediated by mammalian target of rapamycin complex 1 (mTORC1). 33258451 chr22 39516712 39518712 ATF4 We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. human lymphoid High+Lowthroughput Small molecule cognitive enhancer reverses age-related memory decline in mice 不相关 Neurodegenerative diseases T cell E_02_0576 Western blot analysis, electrophysiology, fluorescent spine imaging preparation, qPCR analysis, qPCR analysis We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Immunohistochemical staining We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. 蛋白质印迹分析，电生理学，荧光脊柱成像准备，qPCR 分析，qPCR 分析 ATF4 We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. 33257422 chr5 147204073 147206073 Pdx1 Pancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. mouse High+Lowthroughput Genetically engineered pigs manifesting pancreatic agenesis with severe diabetes 不相关 diabetes germ line cell,exocrine cell E_02_0577 Genotyping, biochemical analysis, RNA isolation, complementary DNA (cDNA) synthesis and quantitative real-time PCR (qPCR) Pancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Pancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. Immunohistochemical staining Pancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. 基因分型，生化分析，RNA 分离、互补 DNA （cDNA） 合成和定量实时荧光定量 PCR （qPCR） Pdx1 Pancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. 33240378 chr3 12284469 12286469 PPARG Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. human connective High+Lowthroughput Impact of Proliferator-Activated Receptor γ Gene Polymorphisms on Risk of Schizophrenia: A Case-Control Study and Computational Analyses 相关 rs1801282,rs3856806 Schizophrenia Fat cell (adipocyte),macrophage E_02_0578 Genotyping Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. Immunohistochemical staining Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. 基因分型 PPARG Peroxisome proliferator-activated receptor-γ (PPARG) mainly regulates lipid and glucose metabolisms while it is constitutively expressed in rat primary microglial cultures. 33238114 chr2 25224801 25226801 DNMT3A Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. human High+Lowthroughput DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders 不相关 autism immune cell E_02_0579 Immunocytochemistry, in vitro radioactive methyltransferase assay, Western blot, chromatin immunoprecipitation, RNA sequencing analysis Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. Immunohistochemical staining Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. 免疫细胞化学，体外放射性甲基转移酶测定，蛋白质印迹，染色质免疫沉淀，RNA测序分析 DNMT3A Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. 33232675 chr19 47605479 47607479 BICRA We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. human Nervous High+Lowthroughput BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms 不相关 Intellectual disability neuroglioform cell,neuron E_02_0580 Immunoprecipitation mass spectrometry We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. Immunohistochemical staining We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. 免疫沉淀-质谱 BICRA We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. 33232656 chr3 187718918 187720918 BCL6 Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors, and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B-cells. human lymphoid High+Lowthroughput Unique Immune Cell Coactivators Specify Locus Control Region Function and Cell Stage 不相关 B cell lymphoma B cell,lymphocyte E_02_0581 Cross linked chromatin immunoprecipitation (chip), gene knockdown, CRISPR / cas9, RNA isolation, cDNA preparation and quantitative real-time PCR (qPCR), luciferase assay, immunoprecipitation and immunoprecipitation mass spectrometry (ip-ms), electrophoretic mobility shift assay (EMSA Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors, and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B-cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors, and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B-cells. Immunohistochemical staining Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors, and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B-cells. 交联染色质免疫沉淀 （ChIP），基因敲降，CRISPR/Cas9，RNA 分离、cDNA 制备和定量实时荧光定量 PCR （qPCR），荧光素酶测定，免疫沉淀和免疫沉淀质谱（IP-MS），电泳迁移率转移测定 （EMSA） BCL6 Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors, and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B-cells. 33222501 chr14 24332849 24334849 RIPK3 Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which acts as a master switch that controls whether the cell undergoes NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)–dependent inflammation, caspase-dependent apoptosis, or necroptosis in response to extracellular stimuli. human Lymphoid tissues, epithelial High+Lowthroughput RIPK1 Expression Associates With Inflammation in Early Atherosclerosis in Humans and Can Be Therapeutically Silenced to Reduce NF-κB Activation and Atherogenesis in Mice 不相关 atherosclerosis endothelial cell,macrophage E_02_0582 Western blot, cell viability assay, NF- κ B luciferase assay, immunofluorescence of HUVECs Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which acts as a master switch that controls whether the cell undergoes NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)–dependent inflammation, caspase-dependent apoptosis, or necroptosis in response to extracellular stimuli. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which acts as a master switch that controls whether the cell undergoes NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)–dependent inflammation, caspase-dependent apoptosis, or necroptosis in response to extracellular stimuli. Immunohistochemical staining Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which acts as a master switch that controls whether the cell undergoes NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)–dependent inflammation, caspase-dependent apoptosis, or necroptosis in response to extracellular stimuli. 蛋白质印迹，细胞活力检测，NF-κB荧光素酶测定，HUVECs的免疫荧光 RIPK3 Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which acts as a master switch that controls whether the cell undergoes NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)–dependent inflammation, caspase-dependent apoptosis, or necroptosis in response to extracellular stimuli. 33195520 chr1 109306543 109308543 SORT1 Although culture with POA, OA, and LA led to lower very low density lipoprotein (VLDL) concentration in cell culture medium, POA and OA led to greater concentrations of triacylglycerol, protein abundance of sterol regulatory element-binding protein 1c, fatty acid synthase, acetyl coenzyme A carboxylase 1, ApoB100, and sortilin 1 (SORT1). human hepatic High+Lowthroughput Lipid Accumulation and Injury in Primary Calf Hepatocytes Challenged With Different Long-Chain Fatty Acids 不相关 Nonalcoholic fatty liver disease hepatocyte E_02_0583 Ribonucleic acid extraction and polymerase chain reaction, Western blot assay, biochemical and oxidative stress index assays, lipid droplet confocal microscopy, reactive oxygen species (ROS) assay Although culture with POA, OA, and LA led to lower very low density lipoprotein (VLDL) concentration in cell culture medium, POA and OA led to greater concentrations of triacylglycerol, protein abundance of sterol regulatory element-binding protein 1c, fatty acid synthase, acetyl coenzyme A carboxylase 1, ApoB100, and sortilin 1 (SORT1). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Although culture with POA, OA, and LA led to lower very low density lipoprotein (VLDL) concentration in cell culture medium, POA and OA led to greater concentrations of triacylglycerol, protein abundance of sterol regulatory element-binding protein 1c, fatty acid synthase, acetyl coenzyme A carboxylase 1, ApoB100, and sortilin 1 (SORT1). Immunohistochemical staining Although culture with POA, OA, and LA led to lower very low density lipoprotein (VLDL) concentration in cell culture medium, POA and OA led to greater concentrations of triacylglycerol, protein abundance of sterol regulatory element-binding protein 1c, fatty acid synthase, acetyl coenzyme A carboxylase 1, ApoB100, and sortilin 1 (SORT1). 核糖核酸提取和聚合酶链反应，蛋白质印迹测定，生化和氧化应激指数检测，脂滴共聚焦显微镜，活性氧 （ROS） 测定 SORT1 Although culture with POA, OA, and LA led to lower very low density lipoprotein (VLDL) concentration in cell culture medium, POA and OA led to greater concentrations of triacylglycerol, protein abundance of sterol regulatory element-binding protein 1c, fatty acid synthase, acetyl coenzyme A carboxylase 1, ApoB100, and sortilin 1 (SORT1). 33195246 chr4 108044684 108046684 LEF1 This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. human Nervous High+Lowthroughput Dose-Dependent and Subset-Specific Regulation of Midbrain Dopaminergic Neuron Differentiation by LEF1-Mediated WNT1/b-Catenin Signaling 不相关 Parkinson's disease neural cell E_02_0584 Microarray analysis, immunohistochemistry / immunocytochemistry, VM primary cultures and rspo2 / edu treatment, Western blotting, chromatin immunoprecipitation polymerase chain reaction, transfection, luciferase reporter assays and site directed mutagenesis, fast polymerase chain reaction This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. Immunohistochemical staining This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. 微阵列分析，免疫组化/免疫细胞化学，VM 原代培养和 RSPO2/EdU 治疗，蛋白质印迹，染色质免疫沉淀-聚合酶链反应，转染、荧光素酶报告检测和定点诱变，快速聚合酶链反应 LEF1 This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. 33188077 chr11 53519379 53521379 Il13 Mast cells express Il13 mRNA and produce IL-13 protein in response to antigenic stimulation. mouse lymphoid High+Lowthroughput The Clusters of Transcription Factors NFATC2, STAT5, GATA2, AP1, RUNX1 and EGR2 Binding Sites at the Induced Il13 Enhancers Mediate Il13 Gene Transcription in Response to Antigenic Stimulation 不相关 Allergic inflammation leukocyte E_02_0585 Chromatin immunoprecipitation chip, Omni ATAC SEQ, transcription factor binding motif analysis, cell transfection Mast cells express Il13 mRNA and produce IL-13 protein in response to antigenic stimulation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mast cells express Il13 mRNA and produce IL-13 protein in response to antigenic stimulation. Immunohistochemical staining Mast cells express Il13 mRNA and produce IL-13 protein in response to antigenic stimulation. 染色质免疫沉淀 ChIP，Omni-ATAC-seq，转录因子结合基序分析，细胞转染 Il13 Mast cells express Il13 mRNA and produce IL-13 protein in response to antigenic stimulation. 33187138 chr6 47504488 47506488 Ezh2 Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. mouse Nervous High+Lowthroughput Downregulation of the Polycomb-Associated Methyltransferase Ezh2 during Maturation of Hippocampal Neurons Is Mediated by MicroRNAs Let-7 and miR-124 不相关 neuronal stem cell,neuron E_02_0586 MicroRNA expression analysis using microarrays, microRNA quantification, transient transfection, reverse transcriptase and real-time quantitative fluorescent PCR (RT qPCR), luciferase reporter assays Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. Immunohistochemical staining Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. 使用微阵列的MicroRNA表达分析，微量RNA定量，瞬时转染，逆转录酶和实时定量荧光定量 PCR （RT-qPCR），荧光素酶报告基因测定 Ezh2 Ezh2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2) which mediates epigenetic gene silencing through depositing the mark histone H3 lysine 27 trimethylation (H3K27me3) at target genomic sequences. 33183330 chr1 247412986 247414986 NLRP3 Inflammatory NFκB [54–56] and MAPK [55, 57] signaling increase the expression of the scaffold protein NOD-like receptor pyrin domain-containing 3 (NLRP3). human High+Lowthroughput Adenosine A(3) receptor as a novel therapeutic target to reduce secondary events and improve neurocognitive functions following traumatic brain injury 不相关 Traumatic brain injury astrocyte, granulocyte E_02_0587 Western blot analysis, immunofluorescence staining Inflammatory NFκB [54–56] and MAPK [55, 57] signaling increase the expression of the scaffold protein NOD-like receptor pyrin domain-containing 3 (NLRP3). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inflammatory NFκB [54–56] and MAPK [55, 57] signaling increase the expression of the scaffold protein NOD-like receptor pyrin domain-containing 3 (NLRP3). Immunohistochemical staining Inflammatory NFκB [54–56] and MAPK [55, 57] signaling increase the expression of the scaffold protein NOD-like receptor pyrin domain-containing 3 (NLRP3). 蛋白质印迹分析，免疫荧光染色 NLRP3 Inflammatory NFκB [54–56] and MAPK [55, 57] signaling increase the expression of the scaffold protein NOD-like receptor pyrin domain-containing 3 (NLRP3). 33175598 chr5 115564894 115566894 Msi1 Evolutionarily conserved RNA-binding protein Musashi1 (Msi1) can regulate developmentally relevant genes. mouse Epithelial High+Lowthroughput Constitutive Musashi1 expression impairs mouse postnatal development and intestinal homeostasis 不相关 cancer epithelial cell, goblet cell E_02_0588 Gene knockdown, immunofluorescence, immunoperoxidase staining, RNA in situ hybridization, cDNA generation, and gene expression analysis Evolutionarily conserved RNA-binding protein Musashi1 (Msi1) can regulate developmentally relevant genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Evolutionarily conserved RNA-binding protein Musashi1 (Msi1) can regulate developmentally relevant genes. Immunohistochemical staining Evolutionarily conserved RNA-binding protein Musashi1 (Msi1) can regulate developmentally relevant genes. 基因敲降，免疫荧光，免疫过氧化物酶染色，RNA原位杂交，cDNA生成和基因表达分析 Msi1 Evolutionarily conserved RNA-binding protein Musashi1 (Msi1) can regulate developmentally relevant genes. 33171905 chr6 143937411 143939411 PLAGL1 The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. human Epithelial High+Lowthroughput Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta 不相关 Gestational diabetes mellitus endothelial cell E_02_0589 Immunohistochemical staining, siRNA knockdown and qPCR, htr-8 / svneo RNA seq The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. Immunohistochemical staining The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. 免疫组化染色，siRNA敲低和qPCR，HTR-8/SVneo RNA-seq PLAGL1 The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. 33146943 chr9 117701168 117703168 TLR4 Li‐EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase‐2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. human High+Lowthroughput Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation 不相关 cerebral ischemia mesenchymal stem cell E_02_0590 Preparation of EVs using regulatory media of polyethylene glycol, characterization of MSC derived EVs, measurement of proteasome activity, Western blot analysis, real-time polymerase chain reaction Li‐EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase‐2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Li‐EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase‐2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. Immunohistochemical staining Li‐EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase‐2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. 使用聚乙二醇的调节介质制备EV，MSC衍生EV的表征，蛋白酶体活性的测量，蛋白质印记分析，实时聚合酶链反应 TLR4 Li‐EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase‐2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. 33144667 chr6 89923787 89925787 BACH2 The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 T+reg cells and suppressing the effector functions of multiple effector T cell (Teff) lineages. human lymphoid High+Lowthroughput A cell-based bioluminescence assay reveals dose-dependent and contextual repression of AP-1-driven gene expression by BACH2 不相关 cancer T cell E_02_0591 Sanger sequencing and data analysis, luciferase assay, Western blot, rgfp966 inhibitor treatment The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 T+reg cells and suppressing the effector functions of multiple effector T cell (Teff) lineages. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 T+reg cells and suppressing the effector functions of multiple effector T cell (Teff) lineages. Immunohistochemical staining The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 T+reg cells and suppressing the effector functions of multiple effector T cell (Teff) lineages. 桑格测序和数据分析，荧光素酶测定，蛋白质印迹，RGFP966 抑制剂治疗 BACH2 The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 T+reg cells and suppressing the effector functions of multiple effector T cell (Teff) lineages. 33143661 chr18 38066305 38068305 Hdac3 The present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice. mouse High+Lowthroughput Involvement of Hdac3-mediated inhibition of microRNA cluster 17-92 in bronchopulmonary dysplasia development 不相关 Bronchial dysplasia desmocyte，lung cancer cell E_02_0592 Immunohistochemistry, immunofluorescence staining of microvessel density (MVD), RNA extraction and gene expression extraction, Western blot analysis, chromatin immunoprecipitation (chip) assay The present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice. Immunohistochemical staining The present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice. 免疫组化，微血管密度（MVD）的免疫荧光染色，RNA提取和基因表达提取，蛋白质印记分析，染色质免疫沉淀（ChIP）测定 Hdac3 The present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice. 33143524 chr10 13096741 13098741 OPTN OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. human High+Lowthroughput Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3 不相关 Senile osteoporosis mesenchymal stem cell，bone cell E_02_0593 Three point bending test, LC-MS analysis and data analysis, ROS detection, QRT PCR, enzyme-linked immunosorbent assay (ELISA), sa-glb1 staining. Histochemical and immunohistochemical staining, Western blot analysis, CO immunoprecipitation analysis OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Immunohistochemical staining OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. 三点弯曲试验，LC-MS 分析和数据分析，ROS 检测，qRT-PCR，酶联免疫吸附测定 （ELISA），SA-GLB1 染色。组织化学和免疫组织化学染色，免疫印迹分析，共免疫沉淀分析 OPTN OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. 33139491 chrX 7437220 7439220 Foxp3 During Treg differentiation, a CpG-rich Foxp3 intronic enhancer, conserved noncoding sequence 2 (CNS2), is activated via DNA demethylation to establish epigenetic memory of Foxp3 expression to protect Treg identity. mouse lymphoid High+Lowthroughput Cutting Edge: CRISPR-Based Transcriptional Regulators Reveal Transcription-Dependent Establishment of Epigenetic Memory of Foxp3 in Regulatory T Cells 不相关 Immune disorders T cell E_02_0594 Retroviral transduction, in vitro suppression assay During Treg differentiation, a CpG-rich Foxp3 intronic enhancer, conserved noncoding sequence 2 (CNS2), is activated via DNA demethylation to establish epigenetic memory of Foxp3 expression to protect Treg identity. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq During Treg differentiation, a CpG-rich Foxp3 intronic enhancer, conserved noncoding sequence 2 (CNS2), is activated via DNA demethylation to establish epigenetic memory of Foxp3 expression to protect Treg identity. Immunohistochemical staining During Treg differentiation, a CpG-rich Foxp3 intronic enhancer, conserved noncoding sequence 2 (CNS2), is activated via DNA demethylation to establish epigenetic memory of Foxp3 expression to protect Treg identity. 逆转录病毒转导，体外抑制试验 Foxp3 During Treg differentiation, a CpG-rich Foxp3 intronic enhancer, conserved noncoding sequence 2 (CNS2), is activated via DNA demethylation to establish epigenetic memory of Foxp3 expression to protect Treg identity. 33137828 chr19 33792836 33794836 KCTD15 We identified miR-381, which specifically targets the 3′ untranslated region (3′ UTR) of potassium channel tetramerization-domain-containing 15 (KCTD15) , and verified the mechanism regulating its expression and participation in adipogenesis. We used a dual luciferase-reporter assay and transfection-mediated miR-381 overexpression and inhibition in Yanbian yellow cattle preadipocytes to investigate the role of miR-381 in adipogenesis. human connective High+Lowthroughput miR-381 Targets KCTD15 to Regulate Bovine Preadipocyte Differentiation In Vitro 不相关 fat cell E_02_0595 Cell transfection, dual luciferase reporter assay, RNA extraction and qPCR analysis We identified miR-381, which specifically targets the 3′ untranslated region (3′ UTR) of potassium channel tetramerization-domain-containing 15 (KCTD15) , and verified the mechanism regulating its expression and participation in adipogenesis. We used a dual luciferase-reporter assay and transfection-mediated miR-381 overexpression and inhibition in Yanbian yellow cattle preadipocytes to investigate the role of miR-381 in adipogenesis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identified miR-381, which specifically targets the 3′ untranslated region (3′ UTR) of potassium channel tetramerization-domain-containing 15 (KCTD15) , and verified the mechanism regulating its expression and participation in adipogenesis. We used a dual luciferase-reporter assay and transfection-mediated miR-381 overexpression and inhibition in Yanbian yellow cattle preadipocytes to investigate the role of miR-381 in adipogenesis. Immunohistochemical staining We identified miR-381, which specifically targets the 3′ untranslated region (3′ UTR) of potassium channel tetramerization-domain-containing 15 (KCTD15) , and verified the mechanism regulating its expression and participation in adipogenesis. We used a dual luciferase-reporter assay and transfection-mediated miR-381 overexpression and inhibition in Yanbian yellow cattle preadipocytes to investigate the role of miR-381 in adipogenesis. 细胞转染，Dual luciferase-reporter assay，RNA extraction and qPCR analysis KCTD15 We identified miR-381, which specifically targets the 3′ untranslated region (3′ UTR) of potassium channel tetramerization-domain-containing 15 (KCTD15) , and verified the mechanism regulating its expression and participation in adipogenesis. We used a dual luciferase-reporter assay and transfection-mediated miR-381 overexpression and inhibition in Yanbian yellow cattle preadipocytes to investigate the role of miR-381 in adipogenesis. 33126652 chr5 176808090 176810090 UNC5A Our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A. human Cancer High+Lowthroughput O-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of UNC5A during Colon Carcinogenesis 不相关 Colon cancer colon cancer cell E_02_0596 Immunohistochemical staining, quantification, RT-PCR quantification, extraction of total and chromatin bound proteins, Western blotting and antibodies, luciferase promoter activity assay, CO immunoprecipitation Our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A. Immunohistochemical staining Our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A. 免疫组织化学染色、定量，RT-PCR定量分析，总蛋白和染色质结合蛋白的提取，蛋白质印迹和抗体，荧光素酶启动子活性测定，共免疫沉淀 UNC5A Our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A. 33097694 chr3 147382975 147384975 ZIC4 Inactivation of tumor suppressor gene played critical roles in the development and progression of human hepatocellular carcinoma (HCC). Zic family member 4 (ZIC4) is transcription factor and plays an important role in the developmental process. human Cancer High+Lowthroughput Epigenetic silencing of ZIC4 contributes to cancer progression in hepatocellular carcinoma 不相关 Hepatocellular carcinoma hepatocellular carcinoma cell E_02_0597 Transfection of shRNA, DNA methylation analysis, RNA extraction and quantitative reverse transcription polymerase chain reaction (QRT PCR), Western blot analysis, chromatin immunoprecipitation discovery, flow cytometry Inactivation of tumor suppressor gene played critical roles in the development and progression of human hepatocellular carcinoma (HCC). Zic family member 4 (ZIC4) is transcription factor and plays an important role in the developmental process. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inactivation of tumor suppressor gene played critical roles in the development and progression of human hepatocellular carcinoma (HCC). Zic family member 4 (ZIC4) is transcription factor and plays an important role in the developmental process. Immunohistochemical staining Inactivation of tumor suppressor gene played critical roles in the development and progression of human hepatocellular carcinoma (HCC). Zic family member 4 (ZIC4) is transcription factor and plays an important role in the developmental process. 转染 shRNA，DNA甲基化分析，RNA提取和定量逆转录-聚合酶链反应（qRT-PCR），蛋白质印记分析，染色质免疫沉淀发现，流式细胞术 ZIC4 Inactivation of tumor suppressor gene played critical roles in the development and progression of human hepatocellular carcinoma (HCC). Zic family member 4 (ZIC4) is transcription factor and plays an important role in the developmental process. 33096182 chr14 35275853 35277853 PSMA6 It was also found that the transcription factors CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma (PPARG), as well as the key genes related to adipogenesis, were upregulated, while the genes related to fat oxidation were significantly downregulated, which indicated that the PSMA6 gene could stimulate the differentiation of preadipocytes. human connective High+Lowthroughput The potential role of PSMA6 in modulating fat deposition in pigs by promoting preadipocyte proliferation and differentiation 不相关 Fat deposition adipocyte ，desmocyte E_02_0598 Oil Red O staining，cDNA preparation and quantitative real-time PCR (qRT-PCR) assay It was also found that the transcription factors CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma (PPARG), as well as the key genes related to adipogenesis, were upregulated, while the genes related to fat oxidation were significantly downregulated, which indicated that the PSMA6 gene could stimulate the differentiation of preadipocytes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq It was also found that the transcription factors CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma (PPARG), as well as the key genes related to adipogenesis, were upregulated, while the genes related to fat oxidation were significantly downregulated, which indicated that the PSMA6 gene could stimulate the differentiation of preadipocytes. Immunohistochemical staining It was also found that the transcription factors CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma (PPARG), as well as the key genes related to adipogenesis, were upregulated, while the genes related to fat oxidation were significantly downregulated, which indicated that the PSMA6 gene could stimulate the differentiation of preadipocytes. Oil Red O staining，cDNA preparation and quantitative real-time PCR (qRT-PCR) assay PSMA6 It was also found that the transcription factors CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma (PPARG), as well as the key genes related to adipogenesis, were upregulated, while the genes related to fat oxidation were significantly downregulated, which indicated that the PSMA6 gene could stimulate the differentiation of preadipocytes. 33086062 chr12 49016248 49018248 KMT2D Histone methyltransferase KMT2D harbors frequent loss-of-function somatic point mutations in several tumor types, including melanoma. human High+Lowthroughput Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma 不相关 tumour melanocyte，melanoma cell E_02_0599 Inhibitor treatment experiments, chip SEQ chromatin immunoprecipitation, TCGA RNA SEQ data analysis, immunohistochemistry Histone methyltransferase KMT2D harbors frequent loss-of-function somatic point mutations in several tumor types, including melanoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Histone methyltransferase KMT2D harbors frequent loss-of-function somatic point mutations in several tumor types, including melanoma. Immunohistochemical staining Histone methyltransferase KMT2D harbors frequent loss-of-function somatic point mutations in several tumor types, including melanoma. 抑制剂治疗实验，ChIP-Seq染色质免疫沉淀，TCGA RNA-Seq数据分析，免疫组化 KMT2D Histone methyltransferase KMT2D harbors frequent loss-of-function somatic point mutations in several tumor types, including melanoma. 33084574 chr1 26690504 26692504 ARID1A In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. human Lymphoid tissue, liver High+Lowthroughput ARID1A loss in adult hepatocytes activates β-catenin-mediated erythropoietin transcription 不相关 erythrocyte，stem cell E_02_0600 Immunohistochemistry and in situ hybridization experiments, enzyme-linked immunosorbent assay (ELISA), cell transfection, stimulation and luciferase assays, RNA extraction and quantitative RT-PCR, protein extracts and Western blotting, electrophoretic mobility shift assay (EMSA), flow cytometry and forming unit erythroid (CFU-E) assays, chromatin immunoprecipitation (chip) and ATAC qPCR assays were performed In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Immunohistochemical staining In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. 免疫组化和原位杂交实验，酶联免疫吸附测定（ELISA），细胞转染、刺激和荧光素酶检测，RNA 提取和定量 RT-PCR，蛋白质提取物和蛋白质印迹，电泳迁移率移位测定 （EMSA），流式细胞术和成形单元红系 （CFU-E） 检测，染色质免疫沉淀 （ChIP） 和 ATAC-qPCR 检测 ARID1A In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. 33083767 chr17 27055027 27057027 Nkx2-5 We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. mouse Musculature High+Lowthroughput Divergent Transcription of the Nkx2-5 Locus Generates Two Enhancer RNAs with Opposing Functions 不相关 heart failure cardiac muscle cell (sensu Arthopoda) E_02_0601 RNA sequencing (RNA SEQ), quantitative PCR (qPCR), cell fractionation, rna-fish, Western blotting, fluorescent immunoassay We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. Immunohistochemical staining We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. RNA测序（RNA-seq），定量PCR（qPCR），细胞分馏，RNA-FISH，蛋白质印记，荧光免疫分析 Nkx2-5 We have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription. 33078455 chr13 73052160 73054160 KLF5 These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. human connective High+Lowthroughput Regulation of adipocyte differentiation by clusterin-mediated Krüppel-like factor 5 stabilization 不相关 fat cell，mesenchymal stem cell E_02_0602 RNA isolation and quantitative real_x0002_time PCR (qRT-PCR)，Luciferase reporter assay，20S proteasome activity assay These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. Immunohistochemical staining These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. RNA isolation and quantitative real_x0002_time PCR (qRT-PCR)，Luciferase reporter assay，20S proteasome activity assay KLF5,CLU,Cebpa,Pparg These results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5.;CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa).;CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa).;CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa). 33033262 chr9 107482552 107484552 KLF4 Establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription. human High+Lowthroughput JMJD3 acts in tandem with KLF4 to facilitate reprogramming to pluripotency 不相关 fibroblast E_02_0603 IPSC generation and EPISC to naive PSC transition, plasmid and molecular cloning, ribonucleic acid isolation and RT qPCR, immunofluorescence, Western blot and co immunoprecipitation, flow cytometry analysis, ribonucleic acid sequencing and analysis, chip qPCR and chip SEQ, chip SEQ analysis, chip SEQ analysis, chip SEQ analysis, chip SEQ analysis Establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription. Immunohistochemical staining Establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription. iPSC 生成和 EpiSC 到幼稚 PSC 的过渡，质粒和分子克隆，核糖核酸分离和 RT-qPCR，免疫荧光，蛋白质印迹和共免疫沉淀，流式细胞术分析，核糖核酸序列和分析，ChIP-qPCR 和 ChIP-seq，ChIP-seq 分析，ChIP-seq 分析，ChIP-seq 分析 KLF4,SOX2 Establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription.;JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL and ultimately transcriptional elongation. 31470645 chr8 94246733 94248733 GEM In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). human liver High+Lowthroughput A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice. 否 Respiratory disease Huh 7 cell E_02_0604 PCR, flow cytometry, gene knockdown, Western blot, gel electrophoresis, immunofluorescence staining In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). Immunohistochemical staining In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). PCR,流式细胞术,基因敲降,Western blot,凝胶电泳,免疫荧光染色 GEM In this study, a bacterium (Lactococcus lactis)- like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). 31469428 chr3 51382539 51384539 MANF Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible secretion protein that inhibits inflammation by interacting with the key subunit of nuclear factor kappa light chain enhancer of acti_x005f_x0002_vated B cells (NF-κB) p65. human High+Lowthroughput Mesencephalic Astrocyte-Derived Neurotrophic Factor Inhibits Liver Cancer Through Small Ubiquitin-Related Modifier (SUMO)ylation-Related Suppression of NF-κB/Snail Signaling Pathway and Epithelial-Mesenchymal Transition. 否 Alzheimer's disease E_02_0605 PCR, Western blot, gene knockdown, gel electrophoresis Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible secretion protein that inhibits inflammation by interacting with the key subunit of nuclear factor kappa light chain enhancer of acti_x005f_x0002_vated B cells (NF-κB) p65. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible secretion protein that inhibits inflammation by interacting with the key subunit of nuclear factor kappa light chain enhancer of acti_x005f_x0002_vated B cells (NF-κB) p65. Immunohistochemical staining Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible secretion protein that inhibits inflammation by interacting with the key subunit of nuclear factor kappa light chain enhancer of acti_x005f_x0002_vated B cells (NF-κB) p65. PCR,Western blot,基因敲降,凝胶电泳 MANF Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible secretion protein that inhibits inflammation by interacting with the key subunit of nuclear factor kappa light chain enhancer of acti_x005f_x0002_vated B cells (NF-κB) p65. 31467880 chr12 113389693 113391693 SDS Equal amounts (20 _x005f_xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. human High+Lowthroughput The Antiobesity Effects of Buginawa in 3T3-L1 Preadipocytes and in a Mouse Model of High-Fat Diet-Induced Obesity. 否 Heart disease mesenchymal stem cell E_02_0606 PCR, Western blot, gel electrophoresis Equal amounts (20 _x005f_xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Equal amounts (20 _x005f_xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. Immunohistochemical staining Equal amounts (20 _x005f_xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. PCR,Western blot,凝胶电泳 SDS Equal amounts (20 _x005f_xd835_g) of protein sample were separated on a sodium dodecyl sulfate (SDS) polyacrylamide gel, fol_x0002_lowed by being transferred onto a polyvinylidene fuoride (PVDF) membrane. 31467629 chr17 42310510 42312510 STAT3 One report indicated that the activation of the STAT3 pathway was involved in radiation-induced endothelial inflammation [54], and the DNA-binding activity of STAT3 and the level of phospho_x005f_x0002_Stat3 Tyr (705), but not phospho-Stat3 Ser (727), was reduced in HUVECs after 3 Gy irradiation. human Epithelial High+Lowthroughput Gamma Radiation-Induced Disruption of Cellular Junctions in HUVECs Is Mediated through Affecting MAPK/NF-κB Inflammatory Pathways. 否 Cardiovascular disease endothelial cell E_02_0607 PCR, Western blot, gene knockdown, gel electrophoresis One report indicated that the activation of the STAT3 pathway was involved in radiation-induced endothelial inflammation [54], and the DNA-binding activity of STAT3 and the level of phospho_x005f_x0002_Stat3 Tyr (705), but not phospho-Stat3 Ser (727), was reduced in HUVECs after 3 Gy irradiation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq One report indicated that the activation of the STAT3 pathway was involved in radiation-induced endothelial inflammation [54], and the DNA-binding activity of STAT3 and the level of phospho_x005f_x0002_Stat3 Tyr (705), but not phospho-Stat3 Ser (727), was reduced in HUVECs after 3 Gy irradiation. Immunohistochemical staining One report indicated that the activation of the STAT3 pathway was involved in radiation-induced endothelial inflammation [54], and the DNA-binding activity of STAT3 and the level of phospho_x005f_x0002_Stat3 Tyr (705), but not phospho-Stat3 Ser (727), was reduced in HUVECs after 3 Gy irradiation. PCR,Western blot,基因敲降,凝胶电泳 STAT3 One report indicated that the activation of the STAT3 pathway was involved in radiation-induced endothelial inflammation [54], and the DNA-binding activity of STAT3 and the level of phospho_x005f_x0002_Stat3 Tyr (705), but not phospho-Stat3 Ser (727), was reduced in HUVECs after 3 Gy irradiation. 31467598 chr15 51205539 51207539 CYP19A1 Characterization of the endogenous retrovirus insertion in CYP19A1 associated with henny feathering in chicken. human High+Lowthroughput Characterization of the endogenous retrovirus insertion in CYP19A1 associated with henny feathering in chicken. 否 Other E_02_0608 PCR, Western blot, gel electrophoresis Characterization of the endogenous retrovirus insertion in CYP19A1 associated with henny feathering in chicken. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Characterization of the endogenous retrovirus insertion in CYP19A1 associated with henny feathering in chicken. Immunohistochemical staining Characterization of the endogenous retrovirus insertion in CYP19A1 associated with henny feathering in chicken. PCR,Western blot,凝胶电泳 CYP19A1 Characterization of the endogenous retrovirus insertion in CYP19A1 associated with henny feathering in chicken. 31466317 chr12 9749793 9751793 CD69 The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. human lymph High+Lowthroughput The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. 否 Autoimmune disease Jurkat cell E_02_0609 PCR, gel electrophoresis The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. Immunohistochemical staining The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. PCR,凝胶电泳 CD69 The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1. 31465963 chr3 181709146 181711146 SOX2 Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs. human High+Lowthroughput Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment. 否 Heart disease E_02_0610 ChIP-seq,RNA-seq Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs. Immunohistochemical staining Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs. ChIP-seq,RNA-seq SOX2,POU5F1,NANOG Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs.;Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs.;Enhancers of undifferentiated ESCs cooperatively regulate pluripotency genes, such as POU5F1/ OCT4, NANOG, and SOX2 (Table 1; Figure 6D), which are pluripo_x005f_x0002_tent master transcription factors that can bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent ESCs. 31462713 chr10 22318328 22320328 BMI1 BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. human Epithelial High+Lowthroughput BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. 否 During disease (heart disease in pregnancy) epithelial cell E_02_0611 Chip SEQ, PCR, Western blot, gel electrophoresis BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Immunohistochemical staining BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. ChIP-seq,PCR,Western blot,凝胶电泳 BMI1 BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. 31462429 chr6 36591375 36593375 SRSF3 SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. human kidney High+Lowthroughput SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. 否 Tumour HEK293T cell E_02_0612 Western blot, gel electrophoresis, clip seq SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Immunohistochemical staining SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. Western blot,凝胶电泳,CLIP-seq SRSF3 SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes. 31461843 chr20 3079786 3081786 AVP Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. human Myotome High+Lowthroughput Inhibition of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Hampers the Vasopressin-dependent Stimulation of Myogenic Differentiation. 否 Neuromuscular diseases (certain neuromuscular disorders) L6 cell E_02_0613 PCR, Western blot, gene knockdown, gel electrophoresis Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. Immunohistochemical staining Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. PCR,Western blot,基因敲降,凝胶电泳 AVP Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. 31461456 chr3 160396511 160398511 SMC4 ChIP-Seq was therefore performed on WT and sir2Δ strains in which the condensin subunit Smc4 was C-terminally tagged (13xMyc). human High+Lowthroughput A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure. 否 Other Haploid Cell E_02_0614 PCR, Western blot, gel electrophoresis ChIP-Seq was therefore performed on WT and sir2Δ strains in which the condensin subunit Smc4 was C-terminally tagged (13xMyc). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ChIP-Seq was therefore performed on WT and sir2Δ strains in which the condensin subunit Smc4 was C-terminally tagged (13xMyc). Immunohistochemical staining ChIP-Seq was therefore performed on WT and sir2Δ strains in which the condensin subunit Smc4 was C-terminally tagged (13xMyc). PCR,Western blot,凝胶电泳 SMC4 ChIP-Seq was therefore performed on WT and sir2Δ strains in which the condensin subunit Smc4 was C-terminally tagged (13xMyc). 31456359 chr7 148804691 148806691 EZH2 The aims of this study were to investigate the link between enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC) in preclinical studies and in human lung cancer tissue microarrays. human lung High+Lowthroughput Oncogenic enhancer of zeste homolog 2 is an actionable target in patients with non-small cell lung cancer. 否 Lung adenocarcinoma Lung adenocarcinoma cell E_02_0615 PCR, Western blot, gel electrophoresis The aims of this study were to investigate the link between enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC) in preclinical studies and in human lung cancer tissue microarrays. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The aims of this study were to investigate the link between enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC) in preclinical studies and in human lung cancer tissue microarrays. Immunohistochemical staining The aims of this study were to investigate the link between enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC) in preclinical studies and in human lung cancer tissue microarrays. PCR,Western blot,凝胶电泳 EZH2 The aims of this study were to investigate the link between enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC) in preclinical studies and in human lung cancer tissue microarrays. 31455793 chr3 149159715 149161715 CP At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two β-rings sandwiched between two α-rings. human Immunohistochem High+Lowthroughput Proteasome subunit α1 overexpression preferentially drives canonical proteasome biogenesis and enhances stress tolerance in yeast. 否 Other Immune cell E_02_0616 Immunofluorescence staining, PCR, Western blot, gel electrophoresis At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two β-rings sandwiched between two α-rings. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two β-rings sandwiched between two α-rings. Immunohistochemical staining At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two β-rings sandwiched between two α-rings. 免疫荧光染色,PCR,Western blot,凝胶电泳 CP At the heart of the proteasome is the barrel-shaped 20S core particle (CP), which contains two β-rings sandwiched between two α-rings. 31454988 chr9 127782849 127784849 CDK9 Transcription Repressor Hes1 Contributes to Neuropathic Pain Development by Modifying CDK9/RNAPII-Dependent Spinal mGluR5 Transcription. human Immunohistochem High+Lowthroughput Transcription Repressor Hes1 Contributes to Neuropathic Pain Development by Modifying CDK9/RNAPII-Dependent Spinal mGluR5 Transcription 否 Alzheimer's disease Immune cell E_02_0617 Knockdown, Western blot, PCR, gel electrophoresis Transcription Repressor Hes1 Contributes to Neuropathic Pain Development by Modifying CDK9/RNAPII-Dependent Spinal mGluR5 Transcription. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcription Repressor Hes1 Contributes to Neuropathic Pain Development by Modifying CDK9/RNAPII-Dependent Spinal mGluR5 Transcription. Immunohistochemical staining Transcription Repressor Hes1 Contributes to Neuropathic Pain Development by Modifying CDK9/RNAPII-Dependent Spinal mGluR5 Transcription. 基因敲降,Western blot,PCR,凝胶电泳 CDK9 Transcription Repressor Hes1 Contributes to Neuropathic Pain Development by Modifying CDK9/RNAPII-Dependent Spinal mGluR5 Transcription. 31452712 chr4 71739025 71741025 GC Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. human tumour High+Lowthroughput Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in gastric cancer 否 Cancer (cancer) glioma cell line E_02_0618 Flow cytometry, PCR, gel electrophoresis Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. Immunohistochemical staining Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. 流式细胞术,PCR,凝胶电泳 GC,ESR1,PRMT1,NCOA1,KAT2A Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications.;Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A.;Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A.;Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A.;Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A. 31451060 chr6 106042562 106044562 ATG5 m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7 human embryo High+Lowthroughput m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7 否 Cancer (cancer) 3T3-L1 cell E_02_0619 Knockdown, Western blot, PCR, gel electrophoresis m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7 Immunohistochemical staining m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7 基因敲降,Western blot,PCR,凝胶电泳 ATG5,ATG7 m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7;m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7 31445429 chr6 88137074 88139074 CNR1 Numerous studies have shown that expression of the gene encoding CB1 (CNR1) is highly dynamic with changes in the tissue specific expression of CNR1 associated with brain homeostasis and disease progression. human High+Lowthroughput Disruption of an enhancer associated with addictive behaviour within the cannabinoid receptor-1 gene suggests a possible role in alcohol intake, cannabinoid response and anxiety-related behaviour 是 Cancer (cancer) hippocampal neuron cell E_02_0620 PCR, gel electrophoresis Numerous studies have shown that expression of the gene encoding CB1 (CNR1) is highly dynamic with changes in the tissue specific expression of CNR1 associated with brain homeostasis and disease progression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Numerous studies have shown that expression of the gene encoding CB1 (CNR1) is highly dynamic with changes in the tissue specific expression of CNR1 associated with brain homeostasis and disease progression. Immunohistochemical staining Numerous studies have shown that expression of the gene encoding CB1 (CNR1) is highly dynamic with changes in the tissue specific expression of CNR1 associated with brain homeostasis and disease progression. PCR,凝胶电泳 CNR1 Numerous studies have shown that expression of the gene encoding CB1 (CNR1) is highly dynamic with changes in the tissue specific expression of CNR1 associated with brain homeostasis and disease progression. 31444346 chr2 25157892 25159892 POMC Two pituitary lineages express the hormone precursor pro_x005f_x0002_opiomelanocortin (POMC), the melanotropes and corticotropes. human High+Lowthroughput Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening 否 Cushing disease (Cushing disease) melanophore E_02_0621 RNA-seq,ATAC-seq,ChIP-seq Two pituitary lineages express the hormone precursor pro_x005f_x0002_opiomelanocortin (POMC), the melanotropes and corticotropes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Two pituitary lineages express the hormone precursor pro_x005f_x0002_opiomelanocortin (POMC), the melanotropes and corticotropes. Immunohistochemical staining Two pituitary lineages express the hormone precursor pro_x005f_x0002_opiomelanocortin (POMC), the melanotropes and corticotropes. RNA-seq,ATAC-seq,ChIP-seq POMC Two pituitary lineages express the hormone precursor pro_x005f_x0002_opiomelanocortin (POMC), the melanotropes and corticotropes. 31443565 chr4 140556841 140558841 UCP1 This process, the non-shivering thermogenesis, is mediated by the mitochondrial uncoupling protein 1 (UCP1), which shunts the proton circuit and leads to heat production instead of ATP. human embryo High+Lowthroughput Bitter Orange (Citrus aurantium Linné) Improves Obesity by Regulating Adipogenesis and Thermogenesis through AMPK Activation 否 Cardiovascular diseases (CVD) 3T3-L1 cell E_02_0622 Western blot, PCR, gel electrophoresis This process, the non-shivering thermogenesis, is mediated by the mitochondrial uncoupling protein 1 (UCP1), which shunts the proton circuit and leads to heat production instead of ATP. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq This process, the non-shivering thermogenesis, is mediated by the mitochondrial uncoupling protein 1 (UCP1), which shunts the proton circuit and leads to heat production instead of ATP. Immunohistochemical staining This process, the non-shivering thermogenesis, is mediated by the mitochondrial uncoupling protein 1 (UCP1), which shunts the proton circuit and leads to heat production instead of ATP. Western blot,PCR,凝胶电泳 UCP1 This process, the non-shivering thermogenesis, is mediated by the mitochondrial uncoupling protein 1 (UCP1), which shunts the proton circuit and leads to heat production instead of ATP. 31431624 chr2 113213024 113215024 PAX8 PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma. human kidney High+Lowthroughput PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma 是 Kidney disease renal cell E_02_0623 RNA SEQ, ATAC SEQ, chip SEQ, PCR, gel electrophoresis PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma. Immunohistochemical staining PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma. RNA-seq,ATAC-seq,ChIP-seq,PCR,凝胶电泳 PAX8 PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma. 31430278 chr17 76709990 76711990 JMJD6 Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function. human High+Lowthroughput Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function 否 Other HEK293 cell E_02_0624 Western blot, PCR, gel electrophoresis Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function. Immunohistochemical staining Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function. Western blot,PCR,凝胶电泳 JMJD6 Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function. 31423236 chr1 153659151 153661151 ILF2 ILF2 promotes anchorage independence through direct regulation of PTEN. human tumour High+Lowthroughput ILF2 promotes anchorage independence through direct regulation of PTEN 否 Lung cancr (lung cancer) cancer cell E_02_0625 Western blot, PCR, gel electrophoresis ILF2 promotes anchorage independence through direct regulation of PTEN. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ILF2 promotes anchorage independence through direct regulation of PTEN. Immunohistochemical staining ILF2 promotes anchorage independence through direct regulation of PTEN. Western blot,PCR,凝胶电泳 ILF2,PTEN ILF2 promotes anchorage independence through direct regulation of PTEN.;ILF2 promotes anchorage independence through direct regulation of PTEN. 31420455 chr1 156460657 156462657 MEF2D Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice. human High+Lowthroughput Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice 否 Other HEK293A cell E_02_0626 PCR, gel electrophoresis Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice. Immunohistochemical staining Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice. PCR,凝胶电泳 MEF2D Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice. 31417366 chr5 102751125 102753125 PAM The sgRNA we designed showed high efficiency to guide Cas9 to the PAM sequence, as we observed all editing occurred 30 downstream from the PAM site. human High+Lowthroughput Functional Dissection of C. elegans bZip-Protein CEBP-1 Reveals Novel Structural Motifs Required for Axon Regeneration and Nuclear Import 否 Cancer (cancer) somatic cell E_02_0627 Gene knockdown The sgRNA we designed showed high efficiency to guide Cas9 to the PAM sequence, as we observed all editing occurred 30 downstream from the PAM site. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The sgRNA we designed showed high efficiency to guide Cas9 to the PAM sequence, as we observed all editing occurred 30 downstream from the PAM site. Immunohistochemical staining The sgRNA we designed showed high efficiency to guide Cas9 to the PAM sequence, as we observed all editing occurred 30 downstream from the PAM site. 基因敲降 PAM The sgRNA we designed showed high efficiency to guide Cas9 to the PAM sequence, as we observed all editing occurred 30 downstream from the PAM site. 31415587 chr20 46005862 46007862 MMP9 Occludin de_x005f_x0002_gradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. human Epithelial High+Lowthroughput Proteasome serves as pivotal regulator in Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis 否 Meningoencephalitis (viral meningoencephalitis) epithelial cell E_02_0628 Knockdown, Western blot, PCR, gel electrophoresis Occludin de_x005f_x0002_gradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Occludin de_x005f_x0002_gradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. Immunohistochemical staining Occludin de_x005f_x0002_gradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. 基因敲降,Western blot,PCR,凝胶电泳 MMP9 Occludin de_x005f_x0002_gradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. 31413586 chr4 98876674 98878674 EIF4E AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression. human stomach High+Lowthroughput AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression 否 Gastric cancer SGC-7901 cell E_02_0629 Western blot, PCR, gel electrophoresis AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression. Immunohistochemical staining AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression. Western blot,PCR,凝胶电泳 EIF4E AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression. 31413137 chr5 179611470 179613470 HNRNPH1 HnRNPH1 depletion and mutation of a prominent viral RNA hnRNPH1 binding site decreased use of splice acceptor A1, causing a deficit in Vif expression and replicative fitness. human kidney High+Lowthroughput Genome-Wide Analysis of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) Binding to HIV-1 RNA Reveals a Key Role for hnRNP H1 in Alternative Viral mRNA Splicing 否 Leukemia HEK293T cell E_02_0630 Clip SEQ, PCR, Western blot, gel electrophoresis HnRNPH1 depletion and mutation of a prominent viral RNA hnRNPH1 binding site decreased use of splice acceptor A1, causing a deficit in Vif expression and replicative fitness. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HnRNPH1 depletion and mutation of a prominent viral RNA hnRNPH1 binding site decreased use of splice acceptor A1, causing a deficit in Vif expression and replicative fitness. Immunohistochemical staining HnRNPH1 depletion and mutation of a prominent viral RNA hnRNPH1 binding site decreased use of splice acceptor A1, causing a deficit in Vif expression and replicative fitness. CLIP-seq,PCR,Western blot,凝胶电泳 HNRNPH1,HNRNPA1 HnRNPH1 depletion and mutation of a prominent viral RNA hnRNPH1 binding site decreased use of splice acceptor A1, causing a deficit in Vif expression and replicative fitness.;Notably, hnRNPA1, hnRNPA2 and hnRNPB1 bound to many dispersed sites across viral mRNAs. 31412725 chr2 42491888 42493888 MTA3 The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. human Epithelial High+Lowthroughput Nuclear S-Nitrosylation Defines an Optimal Zone for Inducing Pluripotency 否 Lung disease endothelial cell E_02_0631 PCR, Western blot, gel electrophoresis The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. Immunohistochemical staining The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. PCR,Western blot,凝胶电泳 MTA3 The effect of NO on DNA accessibility is mediated in part by S_x005f_x0002_nitrosylation of nuclear proteins, including MTA3, a subunit of Nucleosome Remodeling Deacetylase (NuRD) complex. 31412252 chr3 181709008 181711008 SOX2 p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. human Epithelial High+Lowthroughput p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas 否 Cancer (cancer) squamous cell(pinacocyte) E_02_0632 Chip SEQ, RNA SEQ, gene knockdown, PCR, Western blot, gel electrophoresis p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. Immunohistochemical staining p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. ChIP-seq,RNA-seq,基因敲降,PCR,Western blot,凝胶电泳 SOX2 p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. 31409603 chr22 30237461 30239461 LIF We found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). human Epithelial High+Lowthroughput Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in oesophageal adenocarcinoma 否 Digestive disease squamous cell(pinacocyte) E_02_0633 ATAC SEQ, chip SEQ, PCR, Western blot, gel electrophoresis We found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). Immunohistochemical staining We found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). ATAC-seq,ChIP-seq,PCR,Western blot,凝胶电泳 LIF We found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). 31408468 chr10 100732618 100734618 PAX2 In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements. human Epithelial High+Lowthroughput The genomic landscape of estrogen receptor α binding sites in mouse mammary gland 否 Breast cancer (breast cancer) epithelial cell E_02_0634 RNA-seq,ChIP-seq In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements. Immunohistochemical staining In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements. RNA-seq,ChIP-seq PAX2,ESRRB,SF1 In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements.;In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements.;In the distal regions (up and down) of ERα binding sites contained a canonical ERE and other motifs including PAX2, ESRRB, SF1, and AP1 motifs as the most highly enriched (p-value <10−30) cis-elements. 31406377 chr6 106967367 106969367 CD24 BM from Zbtb46gfp/+ mice was analyzed by flow cytometry to identify pre-cDC1s as defined by Zbtb46–GFP or CD24 expression. human Immunohistochem High+Lowthroughput An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development 否 Cancer (cancer) dendritic cell E_02_0635 Flow cytometry, ATAC SEQ, RNA SEQ, scrna seq BM from Zbtb46gfp/+ mice was analyzed by flow cytometry to identify pre-cDC1s as defined by Zbtb46–GFP or CD24 expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq BM from Zbtb46gfp/+ mice was analyzed by flow cytometry to identify pre-cDC1s as defined by Zbtb46–GFP or CD24 expression. Immunohistochemical staining BM from Zbtb46gfp/+ mice was analyzed by flow cytometry to identify pre-cDC1s as defined by Zbtb46–GFP or CD24 expression. 流式细胞术,ATAC-seq,RNA-seq,scRNA-seq CD24 BM from Zbtb46gfp/+ mice was analyzed by flow cytometry to identify pre-cDC1s as defined by Zbtb46–GFP or CD24 expression. 31406023 chr8 132864337 132866337 TG Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19al and E2, pro-inflammatory cytokines expression (IL-1β, IL-6, IL-8, and TNF-a), and the expression of CHOP and GRP78. human High+Lowthroughput Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production 否 Metabolic disease (metabolic disease) granulosa cell E_02_0636 PCR, Western blot, gel electrophoresis Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19al and E2, pro-inflammatory cytokines expression (IL-1β, IL-6, IL-8, and TNF-a), and the expression of CHOP and GRP78. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19al and E2, pro-inflammatory cytokines expression (IL-1β, IL-6, IL-8, and TNF-a), and the expression of CHOP and GRP78. Immunohistochemical staining Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19al and E2, pro-inflammatory cytokines expression (IL-1β, IL-6, IL-8, and TNF-a), and the expression of CHOP and GRP78. PCR,Western blot,凝胶电泳 TG Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19al and E2, pro-inflammatory cytokines expression (IL-1β, IL-6, IL-8, and TNF-a), and the expression of CHOP and GRP78. 31405024 chr21 41461360 41463360 TMPRSS2 Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer. human prostate High+Lowthroughput Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer 是 Prostate cancer prostate cancer cell E_02_0637 Chip SEQ, PCR, Western blot, gel electrophoresis Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer. Immunohistochemical staining Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer. ChIP-seq,PCR,Western blot,凝胶电泳 TMPRSS2 Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer. 31400158 chr2 219051311 219053311 IHH Multiple passages of immortalized human hepatocytes (IHH) generated a transformed and tumorigenic phenotype, named as THH. human liver High+Lowthroughput Hepatitis C Virus Mediated Inhibition of miR-181c Activates ATM Signaling and Promotes Hepatocyte Growth 否 Prostate cancer hepatoma cell E_02_0638 PCR, Western blot, gel electrophoresis Multiple passages of immortalized human hepatocytes (IHH) generated a transformed and tumorigenic phenotype, named as THH. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Multiple passages of immortalized human hepatocytes (IHH) generated a transformed and tumorigenic phenotype, named as THH. Immunohistochemical staining Multiple passages of immortalized human hepatocytes (IHH) generated a transformed and tumorigenic phenotype, named as THH. PCR,Western blot,凝胶电泳 IHH Multiple passages of immortalized human hepatocytes (IHH) generated a transformed and tumorigenic phenotype, named as THH. 31399550 chr4 71739194 71741194 GC GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts. human High+Lowthroughput Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation 否 Cancer (cancer) E_02_0639 Western blot, QRT PCR, chip SEQ, gel electrophoresis GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts. Immunohistochemical staining GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts. Western blot,qRT-PCR,ChIP-seq,凝胶电泳 GC GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts. 31399133 chr7 140716650 140718650 BRAF MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells. human High+Lowthroughput MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells 是 Genetic disease embryonic stem cell E_02_0640 Chip SEQ, RNA SEQ, Western blot, PCR, gel electrophoresis MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells. Immunohistochemical staining MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells. ChIP-seq,RNA-seq,Western blot,PCR,凝胶电泳 BRAF,SOX10,SOX2,SOX5,SOX6,SOX9 MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells.;MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells.;Super-enhancers exhibit an exceptionally high density of binding for numerous factors, including the multiprotein Media_x005f_x0002_tor complex and BRG chromatin remodeling complex,transcriptional cofactors, and lineage-determining transcription factors, including members of the SOX transcription factor family in embryonic stem cells(SOX2), neural progenitor cells (SOX2), chondrocytes(SOX9, SOX5/6), and hair follicle stem cells (SOX9);Super-enhancers exhibit an exceptionally high density of binding for numerous factors, including the multiprotein Media_x005f_x0002_tor complex and BRG chromatin remodeling complex,transcriptional cofactors, and lineage-determining transcription factors, including members of the SOX transcription factor family in embryonic stem cells(SOX2), neural progenitor cells (SOX2), chondrocytes(SOX9, SOX5/6), and hair follicle stem cells (SOX9);Super-enhancers exhibit an exceptionally high density of binding for numerous factors, including the multiprotein Media_x005f_x0002_tor complex and BRG chromatin remodeling complex,transcriptional cofactors, and lineage-determining transcription factors, including members of the SOX transcription factor family in embryonic stem cells(SOX2), neural progenitor cells (SOX2), chondrocytes(SOX9, SOX5/6), and hair follicle stem cells (SOX9);Super-enhancers exhibit an exceptionally high density of binding for numerous factors, including the multiprotein Media_x005f_x0002_tor complex and BRG chromatin remodeling complex,transcriptional cofactors, and lineage-determining transcription factors, including members of the SOX transcription factor family in embryonic stem cells(SOX2), neural progenitor cells (SOX2), chondrocytes(SOX9, SOX5/6), and hair follicle stem cells (SOX9) 31398323 chr3 133743662 133745662 TF We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactiva_x005f_x0002_tors. human High+Lowthroughput Enhancer Features that Drive Formation of Transcriptional Condensates 否 Cancer (cancer) Molecular Cell E_02_0641 Flow cytometry, gene knockdown, chip SEQ, PCR, gel electrophoresis We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactiva_x005f_x0002_tors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactiva_x005f_x0002_tors. Immunohistochemical staining We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactiva_x005f_x0002_tors. 流式细胞术,基因敲降,ChIP-seq,PCR,凝胶电泳 TF We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactiva_x005f_x0002_tors. 31396576 chr15 98347480 98349480 Olfr281 However, some exceptions were noted for class II genes: the number of the most ventral class II gene Olfr281- and Olfr124-expressing OSNs increased. mouse High+Lowthroughput Bcl11b controls odorant receptor class choice in mice 否 Other progenitor cell E_02_0642 Gene knockdown, flow cytometry, PCR, RNA SEQ, gel electrophoresis However, some exceptions were noted for class II genes: the number of the most ventral class II gene Olfr281- and Olfr124-expressing OSNs increased. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, some exceptions were noted for class II genes: the number of the most ventral class II gene Olfr281- and Olfr124-expressing OSNs increased. Immunohistochemical staining However, some exceptions were noted for class II genes: the number of the most ventral class II gene Olfr281- and Olfr124-expressing OSNs increased. 基因敲降,流式细胞术,PCR,RNA-seq,凝胶电泳 Olfr281,Olfr124 However, some exceptions were noted for class II genes: the number of the most ventral class II gene Olfr281- and Olfr124-expressing OSNs increased.;However, some exceptions were noted for class II genes: the number of the most ventral class II gene Olfr281- and Olfr124-expressing OSNs increased. 31396342 chr6 125744718 125746718 HEY2 HEY2 acting as a co-repressor with smad3 and smad4 interferes with the response of TGF-beta in hepatocellular carcinoma. human liver High+Lowthroughput HEY2 acting as a co-repressor with smad3 and smad4 interferes with the response of TGF-beta in hepatocellular carcinoma 否 Liver cancer hepatocyte E_02_0643 PCR, Western blot, gene knockdown, gel electrophoresis HEY2 acting as a co-repressor with smad3 and smad4 interferes with the response of TGF-beta in hepatocellular carcinoma. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq HEY2 acting as a co-repressor with smad3 and smad4 interferes with the response of TGF-beta in hepatocellular carcinoma. Immunohistochemical staining HEY2 acting as a co-repressor with smad3 and smad4 interferes with the response of TGF-beta in hepatocellular carcinoma. PCR,Western blot,基因敲降,凝胶电泳 HEY2 HEY2 acting as a co-repressor with smad3 and smad4 interferes with the response of TGF-beta in hepatocellular carcinoma. 31396089 chr18 63120684 63122684 BCL2 Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of Provisional interleukin (IL)-6 and tumor necrosis factor (TNF)- levels in the hippocampus. human Nervous High+Lowthroughput Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment 否 Neurodegenerative disease Neuronal Cell E_02_0644 PCR, Western blot, gel electrophoresis Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of Provisional interleukin (IL)-6 and tumor necrosis factor (TNF)- levels in the hippocampus. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of Provisional interleukin (IL)-6 and tumor necrosis factor (TNF)- levels in the hippocampus. Immunohistochemical staining Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of Provisional interleukin (IL)-6 and tumor necrosis factor (TNF)- levels in the hippocampus. PCR,Western blot,凝胶电泳 BCL2,BAX Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of Provisional interleukin (IL)-6 and tumor necrosis factor (TNF)- levels in the hippocampus.;Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of Provisional interleukin (IL)-6 and tumor necrosis factor (TNF)- levels in the hippocampus. 31395913 chr12 113389560 113391560 SDS We determined the efect of the maceration bufer and the addition of the membrane destabilizer sodium dodecyl sulfate (SDS) or PMA Enhancer during PMA treatments. Suspensions of E. amylovora live, dead, and a mixture of live and dead cells were prepared in plant macerates obtained in either AMB or tenfold diluted AMB (0.1xAMB). human High+Lowthroughput Development of a viability digital PCR protocol for the selective detection and quantification of live Erwinia amylovora cells in cankers 否 plant disease Phytophthora pyrus cell E_02_0645 RNA SEQ, PCR, flow cytometry, gel electrophoresis We determined the efect of the maceration bufer and the addition of the membrane destabilizer sodium dodecyl sulfate (SDS) or PMA Enhancer during PMA treatments. Suspensions of E. amylovora live, dead, and a mixture of live and dead cells were prepared in plant macerates obtained in either AMB or tenfold diluted AMB (0.1xAMB). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We determined the efect of the maceration bufer and the addition of the membrane destabilizer sodium dodecyl sulfate (SDS) or PMA Enhancer during PMA treatments. Suspensions of E. amylovora live, dead, and a mixture of live and dead cells were prepared in plant macerates obtained in either AMB or tenfold diluted AMB (0.1xAMB). Immunohistochemical staining We determined the efect of the maceration bufer and the addition of the membrane destabilizer sodium dodecyl sulfate (SDS) or PMA Enhancer during PMA treatments. Suspensions of E. amylovora live, dead, and a mixture of live and dead cells were prepared in plant macerates obtained in either AMB or tenfold diluted AMB (0.1xAMB). RNA-seq,PCR,流式细胞术,凝胶电泳 SDS We determined the efect of the maceration bufer and the addition of the membrane destabilizer sodium dodecyl sulfate (SDS) or PMA Enhancer during PMA treatments. Suspensions of E. amylovora live, dead, and a mixture of live and dead cells were prepared in plant macerates obtained in either AMB or tenfold diluted AMB (0.1xAMB). 31395854 chr17 72287441 72289441 LINC00511 The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer. human breast High+Lowthroughput The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer 否 Breast cancer (breast cancer) breast cancer cell E_02_0646 PCR, flow cytometry, gel electrophoresis The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer. Immunohistochemical staining The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer. PCR,流式细胞术,凝胶电泳 LINC00511 The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer. 31395079 chr7 36386993 36388993 ANLN ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. human tumour High+Lowthroughput ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis 否 Pancreatic cancer E_02_0647 PCR, Western blot, gel electrophoresis ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. Immunohistochemical staining ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. PCR,Western blot,凝胶电泳 ANLN,EZH2,LASP1 ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis.;ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis.;ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. 31391075 chr3 133743131 133745131 TF Nr5a1 gene (also called Sf-1 or Ad4BP) is a transcription factor (TF) belonging to the nuclear receptor superfamily. human hormone High+Lowthroughput Identification of a pituitary ERα-activated enhancer triggering the expression of Nr5a1, the earliest gonadotrope lineage-specific transcription factor 否 Breast cancer (breast cancer) Gonadotrope cell E_02_0648 Chip SEQ, ATAC SEQ, PCR, gel electrophoresis Nr5a1 gene (also called Sf-1 or Ad4BP) is a transcription factor (TF) belonging to the nuclear receptor superfamily. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Nr5a1 gene (also called Sf-1 or Ad4BP) is a transcription factor (TF) belonging to the nuclear receptor superfamily. Immunohistochemical staining Nr5a1 gene (also called Sf-1 or Ad4BP) is a transcription factor (TF) belonging to the nuclear receptor superfamily. ChIP-seq,ATAC-seq,PCR,凝胶电泳 TF,TBX19,PAX7,POU1F1 Nr5a1 gene (also called Sf-1 or Ad4BP) is a transcription factor (TF) belonging to the nuclear receptor superfamily.;Several TFs are known to promote pituitary stem cells diferentiation into a specifc endocrine lineage: POU1F1 is mandatory for the thyrotrope, somatotrope and lactotrope lineages , TBX19 for the corticotrope, PAX7 for the melanotrope and Nr5a1 for the gon_x005f_x0002_adotrope lineage.;Several TFs are known to promote pituitary stem cells diferentiation into a specifc endocrine lineage: POU1F1 is mandatory for the thyrotrope, somatotrope and lactotrope lineages , TBX19 for the corticotrope, PAX7 for the melanotrope and Nr5a1 for the gon_x005f_x0002_adotrope lineage.;Several TFs are known to promote pituitary stem cells diferentiation into a specifc endocrine lineage: POU1F1 is mandatory for the thyrotrope, somatotrope and lactotrope lineages , TBX19 for the corticotrope, PAX7 for the melanotrope and Nr5a1 for the gon_x005f_x0002_adotrope lineage. 31388625 chr10 88950960 88952960 FAS Antibodies to fatty acid synthase (FAS), stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), and acetyl-CoA carboxylase were from Cell Signaling (Danvers, MA). human High+Lowthroughput Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease 否 Liver disease E_02_0649 RNA SEQ, PCR, Western blot, gel electrophoresis Antibodies to fatty acid synthase (FAS), stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), and acetyl-CoA carboxylase were from Cell Signaling (Danvers, MA). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Antibodies to fatty acid synthase (FAS), stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), and acetyl-CoA carboxylase were from Cell Signaling (Danvers, MA). Immunohistochemical staining Antibodies to fatty acid synthase (FAS), stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), and acetyl-CoA carboxylase were from Cell Signaling (Danvers, MA). RNA-seq,PCR,Western blot,凝胶电泳 FAS Antibodies to fatty acid synthase (FAS), stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), and acetyl-CoA carboxylase were from Cell Signaling (Danvers, MA). 31387996 chr16 69561910 69563910 NFAT5 TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging. human Loose connective High+Lowthroughput TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging 否 Metabolic disease (metabolic disease) 3T3-L1 cell E_02_0650 Western blot, PCR, gel electrophoresis TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging. Immunohistochemical staining TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging. Western blot,PCR,凝胶电泳 NFAT5 TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging. 31380269 chr6 108557326 108559326 FOXO3 Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. human Myotome High+Lowthroughput Selective Heart Irradiation Induces Cardiac Overexpression of the Pro-hypertrophic miR-212 否 Heart disease Cardiac muscle cell E_02_0651 PCR, Western blot, gel electrophoresis Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. Immunohistochemical staining Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. PCR,Western blot,凝胶电泳 FOXO3 Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. 31376680 chr20 5111752 5113752 PCNA TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1. human High+Lowthroughput TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1 否 Inflammatory disease HEK293 cell E_02_0652 PCR, Western blot, gene knockdown, gel electrophoresis TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1. Immunohistochemical staining TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1. PCR,Western blot,基因敲降,凝胶电泳 PCNA,SHPRH TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1.;TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1. 31376159 chr7 22723332 22725332 IL6 The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase-1 and chitinase-like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. human High+Lowthroughput Platelet-rich fibrin elicits an anti-inflammatory response in macrophages in vitro 否 Infectious disease dendritic cell E_02_0653 PCR, gene knockdown, gel electrophoresis The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase-1 and chitinase-like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase-1 and chitinase-like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. Immunohistochemical staining The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase-1 and chitinase-like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. PCR,基因敲降,凝胶电泳 IL6 The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase-1 and chitinase-like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. 31375813 chr8 94246708 94248708 GEM Transposed nuclei are then loaded onto a microfluidic chip for gel bead in emulsion (GEM) generation. human Immunohistochem High+Lowthroughput Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion 是 Autoimmune diseases (autoimmune diseases) Immune cell E_02_0654 Flow cytometry, ATAC SEQ, RNA sseq Transposed nuclei are then loaded onto a microfluidic chip for gel bead in emulsion (GEM) generation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transposed nuclei are then loaded onto a microfluidic chip for gel bead in emulsion (GEM) generation. Immunohistochemical staining Transposed nuclei are then loaded onto a microfluidic chip for gel bead in emulsion (GEM) generation. 流式细胞术,ATAC-seq,RNA-Sseq GEM Transposed nuclei are then loaded onto a microfluidic chip for gel bead in emulsion (GEM) generation. 31375262 chr3 181709143 181711143 SOX2 Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11. human Nervous High+Lowthroughput Heterozygous Mutations in SMARCA2 Reprogram the Enhancer Landscape by Global Retargeting of SMARCA4 否 Cancer (cancer) neural stem cell E_02_0655 Gene knockdown, PCR, gel electrophoresis, Western blot Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11. Immunohistochemical staining Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11. 基因敲降,PCR,凝胶电泳,Western blot SOX2,PAX6,SOX11,SMARCA2,SMARCA4 Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11.;Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11.;Loss of neural differentiation is accom_x005f_x0002_panied by changes in gene expression, including loss of the neu_x0002_ral-specific factors SOX2 and SOX3 and the downstream targets PAX6 and SOX11.;Heterozygous Mutations in SMARCA2 Reprogram the Enhancer Landscape by Global Retargeting of SMARCA4.;Heterozygous Mutations in SMARCA2 Reprogram the Enhancer Landscape by Global Retargeting of SMARCA4. 31373033 chr16 67559225 67561225 CTCF Genome-wide studies have shown that the architectural proteins CTCF and its frequent associated partner cohesin are important for partition of the genome into largely conserved topologically associating domains or TADs on the mega_x005f_x0002_base. human breast High+Lowthroughput C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells 否 Breast cancer (breast cancer) breast cancer cell E_02_0656 Western blot, PCR, gel electrophoresis, chip SEQ, RNA seq Genome-wide studies have shown that the architectural proteins CTCF and its frequent associated partner cohesin are important for partition of the genome into largely conserved topologically associating domains or TADs on the mega_x005f_x0002_base. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genome-wide studies have shown that the architectural proteins CTCF and its frequent associated partner cohesin are important for partition of the genome into largely conserved topologically associating domains or TADs on the mega_x005f_x0002_base. Immunohistochemical staining Genome-wide studies have shown that the architectural proteins CTCF and its frequent associated partner cohesin are important for partition of the genome into largely conserved topologically associating domains or TADs on the mega_x005f_x0002_base. Western blot,PCR,凝胶电泳,ChIP-seq,RNA-seq CTCF Genome-wide studies have shown that the architectural proteins CTCF and its frequent associated partner cohesin are important for partition of the genome into largely conserved topologically associating domains or TADs on the mega_x005f_x0002_base. 31371786 chr10 72689789 72691789 MCU Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. human Nervous High+Lowthroughput Increasing Ca(2+) in photoreceptor mitochondria alters metabolites, accelerates photoresponse recovery, and reveals adaptations to mitochondrial stress 否 Retinal disease Cone Cell E_02_0657 Gene knockdown, PCR, Western blot, gel electrophoresis Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. Immunohistochemical staining Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. 基因敲降,PCR,Western blot,凝胶电泳 MCU Photoreceptor dysfunction and degeneration occur when intracellular Ca2+ homeostasis is disrupted. Ca2+ homeostasis is maintained partly by mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU), which can influence cytosolic Ca2+ signals, stimulate energy production, and trigger apoptosis. Here we discovered that zebrafish cone photoreceptors express unusually low levels of MCU. 31371771 chr16 14520680 14522680 Snai2 A new transgenic reporter line reveals Wnt-dependent Snai2 re-expression and cranial neural crest differentiation in Xenopus. mouse Nervous High+Lowthroughput A new transgenic reporter line reveals Wnt-dependent Snai2 re-expression and cranial neural crest differentiation in Xenopus 否 Cancer (cancer) Neural crest cell E_02_0658 Gene knockdown, PCR, gel electrophoresis A new transgenic reporter line reveals Wnt-dependent Snai2 re-expression and cranial neural crest differentiation in Xenopus. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A new transgenic reporter line reveals Wnt-dependent Snai2 re-expression and cranial neural crest differentiation in Xenopus. Immunohistochemical staining A new transgenic reporter line reveals Wnt-dependent Snai2 re-expression and cranial neural crest differentiation in Xenopus. 基因敲降,PCR,凝胶电泳 Snai2 A new transgenic reporter line reveals Wnt-dependent Snai2 re-expression and cranial neural crest differentiation in Xenopus. 31371698 chr8 127791948 127793948 PVT1 Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. human tumour High+Lowthroughput Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1 否 Renal disease cancer cell E_02_0659 Flow cytometry, gene knockdown, PCR, Western blot, gel electrophoresis Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. Immunohistochemical staining Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. 流式细胞术,基因敲降,PCR,Western blot,凝胶电泳 PVT1,FOXA1 Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1.;Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. 31370857 chr21 34785179 34787179 RUNX1 RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. human colon High+Lowthroughput RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer 否 Colorectal cancer E_02_0660 PCR, Western blot, gene knockdown, gel electrophoresis RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. Immunohistochemical staining RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. PCR,Western blot,基因敲降,凝胶电泳 RUNX1 RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer. 31235524 chr22 23067631 23069631 GNAZ Briefly, the GNAZ gene in previously established HEK293 cells devoid of three Gα families (the Gαs, the Gαq, and the Gα12 families) was mutated by a CRISPR/ Cas9 system using a GNAZ sgRNA-targeting sequence (5’-GATGCGGGTCAGCGAGTCGATGG-3’; including a NGG PAM sequence). Introduction of a 5-bp deletion (frame-shift mutation) into the GNAZ gene was verified by direct sequencing as described elsewhere. human kidney High+Lowthroughput WNT-3A-induced β-catenin signaling does not require signaling through heterotrimeric G proteins 否 Cancer (cancer) HEK293 cell E_02_0661 PCR, Western blot, gel electrophoresis Briefly, the GNAZ gene in previously established HEK293 cells devoid of three Gα families (the Gαs, the Gαq, and the Gα12 families) was mutated by a CRISPR/ Cas9 system using a GNAZ sgRNA-targeting sequence (5’-GATGCGGGTCAGCGAGTCGATGG-3’; including a NGG PAM sequence). Introduction of a 5-bp deletion (frame-shift mutation) into the GNAZ gene was verified by direct sequencing as described elsewhere. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Briefly, the GNAZ gene in previously established HEK293 cells devoid of three Gα families (the Gαs, the Gαq, and the Gα12 families) was mutated by a CRISPR/ Cas9 system using a GNAZ sgRNA-targeting sequence (5’-GATGCGGGTCAGCGAGTCGATGG-3’; including a NGG PAM sequence). Introduction of a 5-bp deletion (frame-shift mutation) into the GNAZ gene was verified by direct sequencing as described elsewhere. Immunohistochemical staining Briefly, the GNAZ gene in previously established HEK293 cells devoid of three Gα families (the Gαs, the Gαq, and the Gα12 families) was mutated by a CRISPR/ Cas9 system using a GNAZ sgRNA-targeting sequence (5’-GATGCGGGTCAGCGAGTCGATGG-3’; including a NGG PAM sequence). Introduction of a 5-bp deletion (frame-shift mutation) into the GNAZ gene was verified by direct sequencing as described elsewhere. PCR,Western blot,凝胶电泳 GNAZ Briefly, the GNAZ gene in previously established HEK293 cells devoid of three Gα families (the Gαs, the Gαq, and the Gα12 families) was mutated by a CRISPR/ Cas9 system using a GNAZ sgRNA-targeting sequence (5’-GATGCGGGTCAGCGAGTCGATGG-3’; including a NGG PAM sequence). Introduction of a 5-bp deletion (frame-shift mutation) into the GNAZ gene was verified by direct sequencing as described elsewhere. 31234917 chrX 67541427 67543427 AR ASC-J9? increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals. human bladder High+Lowthroughput ASC-J9? increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals 否 Muscle invasive disease (muscle invasive disease) TCC-SUP cell E_02_0662 PCR, Western blot, gel electrophoresis ASC-J9? increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ASC-J9? increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals. Immunohistochemical staining ASC-J9? increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals. PCR,Western blot,凝胶电泳 AR,BCL2,BAX ASC-J9? increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals.;The combined therapy increases the expression of the pro-apoptosis BAX gene and cell cycle inhibitor p21 gene, yet suppresses the expression of the pro-survival BCL2 gene in miBCa cells.;The combined therapy increases the expression of the pro-apoptosis BAX gene and cell cycle inhibitor p21 gene, yet suppresses the expression of the pro-survival BCL2 gene in miBCa cells. 31368839 chr7 22723271 22725271 IL6 The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of in_x0002_terleukin 6 (IL6), IL10, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1b(MIP-1b). human High+Lowthroughput Hybrid Mouse Diversity Panel Identifies Genetic Architecture Associated with the Acute Antisense Oligonucleotide-Mediated Inflammatory Response to a 2'-O-Methoxyethyl Antisense Oligonucleotide 是 Neurological disease Primary cell E_02_0663 PCR, flow cytometry The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of in_x0002_terleukin 6 (IL6), IL10, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1b(MIP-1b). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of in_x0002_terleukin 6 (IL6), IL10, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1b(MIP-1b). Immunohistochemical staining The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of in_x0002_terleukin 6 (IL6), IL10, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1b(MIP-1b). PCR,流式细胞术 IL6,IL10 The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of in_x0002_terleukin 6 (IL6), IL10, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1b(MIP-1b).;The acute response was measured 6 h after ASO administration, via evaluation for increased plasma production of in_x0002_terleukin 6 (IL6), IL10, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1b(MIP-1b). 31368152 chr7 148804623 148806623 EZH2 EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells. human Epithelial High+Lowthroughput EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells 否 Oral diseases OSCC cell E_02_0664 Western blot, PCR, gel electrophoresis, flow cytometry EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells. Immunohistochemical staining EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells. Western blot,PCR,凝胶电泳,流式细胞术 EZH2,STAT3,FOXO1 EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells.;EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells.;EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells. 31367252 chr6 4703582 4705582 CDYL CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter. human lung High+Lowthroughput CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter 否 Lung cancer H446 cell E_02_0665 Western blot, PCR, gene knockdown, gel electrophoresis, flow cytometry CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter. Immunohistochemical staining CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter. Western blot,PCR,基因敲降,凝胶电泳,流式细胞术 CDYL CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter. 31363085 chr3 8772830 8774830 RAD18 Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. human embryo High+Lowthroughput Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant 是 Genetic disease HEK293T cell E_02_0666 Gene knockdown, PCR, flow cytometry Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. Immunohistochemical staining Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. 基因敲降,PCR,流式细胞术 RAD18 Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. 31362988 chr1 56491656 56493656 PLPP3 Regulation of PLPP3 gene expression by NF-κB family transcription factors. human Epithelial High+Lowthroughput Regulation of PLPP3 gene expression by NF-κB family transcription factors 否 Coronary artery disease (CHD) endothelial cell E_02_0667 Chip SEQ, Western blot, PCR, gel electrophoresis Regulation of PLPP3 gene expression by NF-κB family transcription factors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Regulation of PLPP3 gene expression by NF-κB family transcription factors. Immunohistochemical staining Regulation of PLPP3 gene expression by NF-κB family transcription factors. ChIP-seq,Western blot,PCR,凝胶电泳 PLPP3 Regulation of PLPP3 gene expression by NF-κB family transcription factors. 31360066 chr13 50079217 50081217 DLEU1 Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis. human High+Lowthroughput Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis 否 Cancer (cancer) glioma cell line E_02_0668 Western blot, PCR, flow cytometry, gel electrophoresis Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis. Immunohistochemical staining Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis. Western blot,PCR,流式细胞术,凝胶电泳 DLEU1 Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis. 32309326 chr8 72017196 72019196 TRPA1 The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. human colonic High+Lowthroughput Early oral nutrition improves postoperative ileus through the TRPA1/CCK1-R-mediated mast cell-nerve axis 不相关 ileus mast cell E_02_0669 Western blot,immunofluorescence,RT-qPCR,Real-Time PCR The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. Immunohistochemical staining The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. Western blot,immunofluorescence,RT-qPCR,Real-Time PCR TRPA1 The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. 32308692 chr6 118561329 118563329 Cacna1c Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. mouse heart High+Lowthroughput The role of miR-711 in cardiac cells in response to oxidative stress and its biogenesis: a study on H9C2 cells 不相关 heart diseases Cardiac cell E_02_0670 qRT-PCR,Western blotting,flow cytometry Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. Immunohistochemical staining Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. qRT-PCR,Western blotting,flow cytometry Cacna1c,FGF14 Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711.;Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. 32619460 chr3 189629192 189631192 TP63 TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines human Esophageal Squamous Cell Carcinoma Cell Lines High+Lowthroughput TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines 不相关 esophageal squamous cell carcinoma Esophageal Squamous Cell Carcinoma Cell E_02_0671 Immunoprecipitation, Immunoblots, Immunohistochemistry TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines Immunohistochemical staining TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines Immunoprecipitation, Immunoblots, Immunohistochemistry TP63,SOX2,KLF5 TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines;TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines;TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines 32596374 chr18 63121061 63123061 BCL2 Treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. human Paraplast-embedded High+Lowthroughput Protection of Lycopene against Embryonic Anomalies and Yolk Sac Placental Vasculogenic Disorders Induced by Nicotine Exposure 不相关 embryonic anomalies E_02_0672 Real-Time PCR,Western Blotting Treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. Immunohistochemical staining Treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. Real-Time PCR,Western Blotting BCL2 Treatment with nicotine resulted in aggravated expressions of the mRNA or protein level of antiapoptotic (BCL2-associated X protein, B-cell lymphoma-extralarge, and caspase 3), anti-inflammatory (nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-alpha), and vasculogenic (vascular endothelial growth factor-alpha, insulin-like growth factor-1, alpha smooth muscle actin, transforming growth factor-beta 1, and hypoxia inducible factor-1 alpha) factors in the embryo and yolk sac placenta. 32594099 chr6 88167556 88169556 Gata2 Gata2 −77 enhancer regulates adult hematopoietic stem cell survival mouse hematopoietic High+Lowthroughput Gata2 -77 enhancer regulates adult hematopoietic stem cell survival 不相关 leukemogenesis hematopoietic stem cell E_02_0673 qRT-PCR,Flow Cytometry Gata2 −77 enhancer regulates adult hematopoietic stem cell survival Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Gata2 −77 enhancer regulates adult hematopoietic stem cell survival Immunohistochemical staining Gata2 −77 enhancer regulates adult hematopoietic stem cell survival qRT-PCR,Flow Cytometry Gata2 Gata2 −77 enhancer regulates adult hematopoietic stem cell survival 32562050 chr14 30871818 30873818 COCH COCH is the most abundantly expressed gene in the cochlea. human High+Lowthroughput Novel loss-of-function mutations in COCH cause autosomal recessive nonsyndromic hearing loss 相关 Nonsyndromic Hearing Loss MDCK cell E_02_0674 RT-PCR，PCR COCH is the most abundantly expressed gene in the cochlea. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq COCH is the most abundantly expressed gene in the cochlea. Immunohistochemical staining COCH is the most abundantly expressed gene in the cochlea. RT-PCR，PCR COCH COCH is the most abundantly expressed gene in the cochlea. 32552830 chr4 8842747 8844747 HMX1 uplications involving the long range HMX1 enhancer are associated with Human isolated bilateral concha-type microtia human High+Lowthroughput Duplications involving the long range HMX1 enhancer are associated with Human isolated bilateral concha-type microtia 相关 rs16891285,rs4696668 Microtia mesenchymal cell E_02_0675 qPCR，Gap-PCR uplications involving the long range HMX1 enhancer are associated with Human isolated bilateral concha-type microtia Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq uplications involving the long range HMX1 enhancer are associated with Human isolated bilateral concha-type microtia Immunohistochemical staining uplications involving the long range HMX1 enhancer are associated with Human isolated bilateral concha-type microtia qPCR，Gap-PCR HMX1 uplications involving the long range HMX1 enhancer are associated with Human isolated bilateral concha-type microtia 32541005 chr14 56797530 56799530 OTX2 The transcription factor Otx2 is required for photoreceptor and bipolar cell formation in the retina. human High+Lowthroughput Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes 不相关 Bipolar cell E_02_0676 Immunohistochemistry The transcription factor Otx2 is required for photoreceptor and bipolar cell formation in the retina. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The transcription factor Otx2 is required for photoreceptor and bipolar cell formation in the retina. Immunohistochemical staining The transcription factor Otx2 is required for photoreceptor and bipolar cell formation in the retina. Immunohistochemistry OTX2 The transcription factor Otx2 is required for photoreceptor and bipolar cell formation in the retina. 32540969 chr8 142907978 142909978 CYP11B2 Effects of intron conversion in the Human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice human brain High+Lowthroughput Effects of intron conversion in the Human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice 相关 rs1799998,rs13257680,rs542092383,rs1563881467 Hypertension H295R cell E_02_0677 real-time PCR，qPCR ，Western blotting，chromatin immunoprecipitation，Immunoblotting Effects of intron conversion in the Human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Effects of intron conversion in the Human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice Immunohistochemical staining Effects of intron conversion in the Human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice real-time PCR，qPCR ，Western blotting，chromatin immunoprecipitation，Immunoblotting CYP11B2 Effects of intron conversion in the Human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice 32538140 chr2 68971694 68973694 GKN1 Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer human gastric epithelial High+Lowthroughput Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer 不相关 gastric cancer Epithelial cell of stomach E_02_0678 QRT-PCR,Immunohistochemistry Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer Immunohistochemical staining Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer QRT-PCR,Immunohistochemistry GKN1,GKN2 Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer;Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer 32499518 chr16 69561736 69563736 NFAT5 Here, we report that the tonicity_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. human synovial High+Lowthroughput TonEBP in dendritic cells mediates pro-inflammatory maturation and Th1/Th17 responses 不相关 rheumatoid arthritis dendritic cell E_02_0679 RT-PCR,qPCR Here, we report that the tonicity_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here, we report that the tonicity_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. Immunohistochemical staining Here, we report that the tonicity_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. RT-PCR,qPCR NFAT5 Here, we report that the tonicity_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. 32493933 chr3 108040258 108042258 CD47 Using ATAC-seq and ChIP-seq, we found that acti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vation of JUN rendered promoters and enhancers of CD47 and PD-L1 accessible. We furtherdetect increased IL-6 that amplified JUN-mediated CD47 enhancer activity and protein expression. human fibrotic lung tissues. High+Lowthroughput Activation of JUN in fibroblasts promotes pro-fibrotic programme and modulates protective immunity 不相关 pulmonary fibrosis stem cell E_02_0680 ATAC-seq,ChIP-seq,Q-PCR Using ATAC-seq and ChIP-seq, we found that acti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vation of JUN rendered promoters and enhancers of CD47 and PD-L1 accessible. We furtherdetect increased IL-6 that amplified JUN-mediated CD47 enhancer activity and protein expression. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Using ATAC-seq and ChIP-seq, we found that acti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vation of JUN rendered promoters and enhancers of CD47 and PD-L1 accessible. We furtherdetect increased IL-6 that amplified JUN-mediated CD47 enhancer activity and protein expression. Immunohistochemical staining Using ATAC-seq and ChIP-seq, we found that acti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vation of JUN rendered promoters and enhancers of CD47 and PD-L1 accessible. We furtherdetect increased IL-6 that amplified JUN-mediated CD47 enhancer activity and protein expression. ATAC-seq,ChIP-seq,Q-PCR CD47 Using ATAC-seq and ChIP-seq, we found that acti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vation of JUN rendered promoters and enhancers of CD47 and PD-L1 accessible. We furtherdetect increased IL-6 that amplified JUN-mediated CD47 enhancer activity and protein expression. 32493794 chrX 49247714 49249714 FOXP3 Targeted insertion of a robust enhancer/promoter proximal to the first coding exon bypassed epigenetic silencing, permitting stable and robust expression of endogenous FOXP3. human lymphoid High+Lowthroughput Gene editing to induce FOXP3 expression in Human CD4(+) T cells leads to a stable regulatory phenotype and function 不相关 autoimmune disease T cell E_02_0681 PCR Targeted insertion of a robust enhancer/promoter proximal to the first coding exon bypassed epigenetic silencing, permitting stable and robust expression of endogenous FOXP3. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Targeted insertion of a robust enhancer/promoter proximal to the first coding exon bypassed epigenetic silencing, permitting stable and robust expression of endogenous FOXP3. Immunohistochemical staining Targeted insertion of a robust enhancer/promoter proximal to the first coding exon bypassed epigenetic silencing, permitting stable and robust expression of endogenous FOXP3. PCR FOXP3 Targeted insertion of a robust enhancer/promoter proximal to the first coding exon bypassed epigenetic silencing, permitting stable and robust expression of endogenous FOXP3. 32458986 chr3 4300716 4302716 SETMAR Mechanistically, RR cells upregulate the Su(var)3-9/enhancer-of-zeste/trithorax (SET) domain and mar_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_iner transposase fusion gene (SETMAR), mediating high levels of H3K36me2 and global euchromatization. human High+Lowthroughput Inhibition of SETMAR-H3K36me2-NHEJ repair axis in residual disease cells prevents glioblastoma recurrence 不相关 Residual disease of glioblastoma Residual cell E_02_0682 real-time PCR Mechanistically, RR cells upregulate the Su(var)3-9/enhancer-of-zeste/trithorax (SET) domain and mar_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_iner transposase fusion gene (SETMAR), mediating high levels of H3K36me2 and global euchromatization. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, RR cells upregulate the Su(var)3-9/enhancer-of-zeste/trithorax (SET) domain and mar_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_iner transposase fusion gene (SETMAR), mediating high levels of H3K36me2 and global euchromatization. Immunohistochemical staining Mechanistically, RR cells upregulate the Su(var)3-9/enhancer-of-zeste/trithorax (SET) domain and mar_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_iner transposase fusion gene (SETMAR), mediating high levels of H3K36me2 and global euchromatization. real-time PCR SETMAR Mechanistically, RR cells upregulate the Su(var)3-9/enhancer-of-zeste/trithorax (SET) domain and mar_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_iner transposase fusion gene (SETMAR), mediating high levels of H3K36me2 and global euchromatization. 32438714 chr8 11674830 11676830 GATA4 These progenitors derive froma mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2 human High+Lowthroughput Contribution of a GATA4-Expressing Hematopoietic Progenitor Lineage to the Adult Mouse Endothelium 不相关 Blastoderm cell E_02_0683 Flow Cytometry， Immunofluorescence These progenitors derive froma mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2 Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These progenitors derive froma mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2 Immunohistochemical staining These progenitors derive froma mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2 Flow Cytometry， Immunofluorescence GATA4 These progenitors derive froma mesodermal lineage characterized by the expression of Gata4 under control of the enhancer G2 32424849 chr3 119521736 119523736 CD80 RNA sequencing re_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein β and CD163, but decreased the expression of CD80 on BMDMs. human colonic High+Lowthroughput Oligosaccharide-dependent anti-inflammatory role of galectin-1 for macrophages in ulcerative colitis 不相关 colitis macrophage E_02_0684 RT-PCR，qPCR，Western blotting，Flow cytometric RNA sequencing re_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein β and CD163, but decreased the expression of CD80 on BMDMs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq RNA sequencing re_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein β and CD163, but decreased the expression of CD80 on BMDMs. Immunohistochemical staining RNA sequencing re_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein β and CD163, but decreased the expression of CD80 on BMDMs. RT-PCR，qPCR，Western blotting，Flow cytometric CD80 RNA sequencing re_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_vealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein β and CD163, but decreased the expression of CD80 on BMDMs. 32417536 chr6 60706042 60708042 Snca Here we tested the hypothesis that Snca deletion in mesenchymal progenitors using the Prrx1Cre (Prrx1, Paired-related homeobox 1) limb enhancer would protect bone mass after OVX. mouse neural High+Lowthroughput Deletion of α-Synuclein in Prrx1-positive cells causes partial loss of function in the central nervous system (CNS) but does not affect ovariectomy induced bone loss 不相关 Bone loss osteoblasts, proerythroblast，macrophage E_02_0685 RT-qPCR，Western blotting Here we tested the hypothesis that Snca deletion in mesenchymal progenitors using the Prrx1Cre (Prrx1, Paired-related homeobox 1) limb enhancer would protect bone mass after OVX. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Here we tested the hypothesis that Snca deletion in mesenchymal progenitors using the Prrx1Cre (Prrx1, Paired-related homeobox 1) limb enhancer would protect bone mass after OVX. Immunohistochemical staining Here we tested the hypothesis that Snca deletion in mesenchymal progenitors using the Prrx1Cre (Prrx1, Paired-related homeobox 1) limb enhancer would protect bone mass after OVX. RT-qPCR，Western blotting Snca Here we tested the hypothesis that Snca deletion in mesenchymal progenitors using the Prrx1Cre (Prrx1, Paired-related homeobox 1) limb enhancer would protect bone mass after OVX. 32405722 chr11 69286483 69288483 Kdm6b our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defned by its TET3-mediated 5-hmC level. mouse High+Lowthroughput TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment 不相关 embryonic stem cell E_02_0686 real-time PCR，qPCR，Western blotting our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defned by its TET3-mediated 5-hmC level. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defned by its TET3-mediated 5-hmC level. Immunohistochemical staining our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defned by its TET3-mediated 5-hmC level. real-time PCR，qPCR，Western blotting Kdm6b our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defned by its TET3-mediated 5-hmC level. 32403381 chr1 115283607 115285607 NGF These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities. human Brain Tissue High+Lowthroughput The Mixture of Gotu Kola, Cnidium Fruit, and Goji Berry Enhances Memory Functions by Inducing Nerve-Growth-Factor-Mediated Actions Both In Vitro and In Vivo 不相关 neuronal cell E_02_0687 Immunohistochemistry， These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities. Immunohistochemical staining These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities. Immunohistochemistry， NGF These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities. 32398354 chr7 136792610 136794610 Ebf3 Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. mouse sternum High+Lowthroughput Transient and lineage-restricted requirement of Ebf3 for sternum ossification 不相关 sternum ossification mesenchymal cell E_02_0688 RT-PCR，RNA-seq，Immunostaining Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. Immunohistochemical staining Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. RT-PCR，RNA-seq，Immunostaining Ebf3 Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. 32385306 chr17 72118341 72120341 SOX9 A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the Mouse, rat, and Human. human bone High+Lowthroughput Biochemical characteristics of the chondrocyte-enriched SNORC protein and its transcriptional regulation by SOX9 不相关 Cartilage E_02_0689 Real-time qPCR， western blotting A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the Mouse, rat, and Human. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the Mouse, rat, and Human. Immunohistochemical staining A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the Mouse, rat, and Human. Real-time qPCR， western blotting SOX9 A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the Mouse, rat, and Human. 32353178 chr11 65420453 65422453 NEAT1 Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. human High+Lowthroughput lncRNA Neat1 Stimulates Osteoclastogenesis Via Sponging miR-7 不相关 osteoporosis peripheral blood mononuclear cell E_02_0690 PCR,RT-PCR Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. Immunohistochemical staining Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. PCR,RT-PCR NEAT1 Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. 32352029 chr1 147538782 147540782 BCL9 BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression human epithelial High+Lowthroughput BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression 不相关 ductal carcinoma in situ epithelial cell E_02_0691 QPCR,ChIP-qPCR,Western blot BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression Immunohistochemical staining BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression QPCR,ChIP-qPCR,Western blot BCL9,STAT3 BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression;BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression 32349972 chr2 15937833 15939833 MYCN We demonstrate this phenotype is mediated through de-repression of a distal PRC2-regulated MYCN enhancer. human Spleen High+Lowthroughput EZH2-Deficient T-cell Acute Lymphoblastic Leukemia Is Sensitized to CHK1 Inhibition through Enhanced Replication Stress 相关 acute lymphoblastic leukemia T cell E_02_0692 Q-PCR,ChIP-qPCR,western blotting We demonstrate this phenotype is mediated through de-repression of a distal PRC2-regulated MYCN enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We demonstrate this phenotype is mediated through de-repression of a distal PRC2-regulated MYCN enhancer. Immunohistochemical staining We demonstrate this phenotype is mediated through de-repression of a distal PRC2-regulated MYCN enhancer. Q-PCR,ChIP-qPCR,western blotting MYCN We demonstrate this phenotype is mediated through de-repression of a distal PRC2-regulated MYCN enhancer. 32332097 chr7 148804478 148806478 EZH2 Inhibition of the epigenetic enzyme Enhancer of Zeste Homolog 2 (EZH2) is both bone-anabolic and osteo-protective. human mineralized High+Lowthroughput Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2 不相关 mesenchymal stem cell E_02_0693 RT-qPCR,Western Blotting Inhibition of the epigenetic enzyme Enhancer of Zeste Homolog 2 (EZH2) is both bone-anabolic and osteo-protective. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Inhibition of the epigenetic enzyme Enhancer of Zeste Homolog 2 (EZH2) is both bone-anabolic and osteo-protective. Immunohistochemical staining Inhibition of the epigenetic enzyme Enhancer of Zeste Homolog 2 (EZH2) is both bone-anabolic and osteo-protective. RT-qPCR,Western Blotting EZH2 Inhibition of the epigenetic enzyme Enhancer of Zeste Homolog 2 (EZH2) is both bone-anabolic and osteo-protective. 32330245 chr3 128476893 128478893 GATA2 The 3q rearrangements reposition a GATA2 enhancer near the EVI1 (or MECOM)locus, which results in both EVI1 overexpression and GATA2 haploinsufficiency. human High+Lowthroughput EVI1 and GATA2 misexpression induced by inv(3)(q21q26) contribute to megakaryocyte-lineage skewing and leukemogenesis 不相关 megakaryocyte-lineage skewing and leukemogenesis progenitor cell E_02_0694 PCR,Flow cytometry,RT-PCR The 3q rearrangements reposition a GATA2 enhancer near the EVI1 (or MECOM)locus, which results in both EVI1 overexpression and GATA2 haploinsufficiency. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The 3q rearrangements reposition a GATA2 enhancer near the EVI1 (or MECOM)locus, which results in both EVI1 overexpression and GATA2 haploinsufficiency. Immunohistochemical staining The 3q rearrangements reposition a GATA2 enhancer near the EVI1 (or MECOM)locus, which results in both EVI1 overexpression and GATA2 haploinsufficiency. PCR,Flow cytometry,RT-PCR GATA2 The 3q rearrangements reposition a GATA2 enhancer near the EVI1 (or MECOM)locus, which results in both EVI1 overexpression and GATA2 haploinsufficiency. 32325694 chr6 137864043 137866043 TNFAIP3 The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3(TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. human High+Lowthroughput TNFAIP3 Deficiency Affects Monocytes, Monocytes-Derived Cells and Microglia in Mice 不相关 Inflammation Monocytes-Derived Cell E_02_0695 PCR，Flow-Cytometry The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3(TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3(TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. Immunohistochemical staining The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3(TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. PCR，Flow-Cytometry TNFAIP3 The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3(TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway. 32321991 chr11 6562441 6564441 Tbrg4 The interdependence of mammary-specific super_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_enhancers and their native promoters facilitates gene activation during pregnancy mouse liver High+Lowthroughput The interdependence of mammary-specific super-enhancers and their native promoters facilitates gene activation during pregnancy 不相关 T cell E_02_0696 qRT-PCR，ChIP-seq The interdependence of mammary-specific super_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_enhancers and their native promoters facilitates gene activation during pregnancy Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The interdependence of mammary-specific super_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_enhancers and their native promoters facilitates gene activation during pregnancy Immunohistochemical staining The interdependence of mammary-specific super_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_enhancers and their native promoters facilitates gene activation during pregnancy qRT-PCR，ChIP-seq Tbrg4 The interdependence of mammary-specific super_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_enhancers and their native promoters facilitates gene activation during pregnancy 32318569 chr5 175437606 175439606 DRD1 we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells human High+Lowthroughput Dopamine Receptor D1 Contributes to Cocaine Epigenetic Reprogramming of Histone Modifications in Male Germ Cells 不相关 male germ cells E_02_0697 RT-PCR，western blot we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells Immunohistochemical staining we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells RT-PCR，western blot DRD1 we report that cocaine-treated male mice showed alterations on specific histone post-translational modifications (PTMs) including increased silent chromatin marks H3K9me3 and H3K27me3 and decreased active enhancer and promoter marks H3K27ac and H3K4me3 in isolated germ cells 32299090 chr22 39517359 39519359 ATF4 Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. human High+Lowthroughput The HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression 不相关 β-thalassemia sickle cell E_02_0698 RT-qPCR,ChIP-seq Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. Immunohistochemical staining Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. RT-qPCR,ChIP-seq ATF4,BCL11A Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable.;Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. 32290615 chr15 97870866 97872866 Col2a1 To investigate the functions of Hck in chondrocytes,transgenic mice expressing a constitutively active form of Hck (HckCA) were generated using the Col2a1 promoter/enhancer. mouse cartilaginous High+Lowthroughput Expression of a Constitutively Active Form of Hck in Chondrocytes Activates Wnt and Hedgehog Signaling Pathways, and Induces Chondrocyte Proliferation in Mice 不相关 mutant lymphoma cell E_02_0699 Real-Time PCR，ChIP To investigate the functions of Hck in chondrocytes,transgenic mice expressing a constitutively active form of Hck (HckCA) were generated using the Col2a1 promoter/enhancer. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq To investigate the functions of Hck in chondrocytes,transgenic mice expressing a constitutively active form of Hck (HckCA) were generated using the Col2a1 promoter/enhancer. Immunohistochemical staining To investigate the functions of Hck in chondrocytes,transgenic mice expressing a constitutively active form of Hck (HckCA) were generated using the Col2a1 promoter/enhancer. Real-Time PCR，ChIP Col2a1 To investigate the functions of Hck in chondrocytes,transgenic mice expressing a constitutively active form of Hck (HckCA) were generated using the Col2a1 promoter/enhancer. 32286279 chr9 14371056 14373056 Kdm4d TADs are further removed until the 2-cell stage before being progressively reestablished.Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. mouse High+Lowthroughput Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos 不相关 somatic cell E_02_0700 Immunostaining，RNA-seq，ChIP-seq TADs are further removed until the 2-cell stage before being progressively reestablished.Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq TADs are further removed until the 2-cell stage before being progressively reestablished.Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. Immunohistochemical staining TADs are further removed until the 2-cell stage before being progressively reestablished.Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. Immunostaining，RNA-seq，ChIP-seq Kdm4d TADs are further removed until the 2-cell stage before being progressively reestablished.Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. 32286261 chr16 67559535 67561535 CTCF In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. human High+Lowthroughput Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes 不相关 E_02_0701 In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. Immunohistochemical staining In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. CTCF In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. 32278722 chr5 75310474 75312474 Pdgfra We established a con_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ditional knockout Mouse for the Pdgfra gene (N-PRa-KO) using a Nestin promoter/enhancer driven Cre recombi_x0002_nase and examined forebrain development. The expression of PDGFRa was efficiently suppressed in the Olig2+cells in N-PRa-KO mice. mouse brain High+Lowthroughput Oligodendrogenesis and Myelin Formation in the Forebrain Require Platelet-derived Growth Factor Receptor-alpha 不相关 Olig2+ E_02_0702 PCR，Immunostainings We established a con_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ditional knockout Mouse for the Pdgfra gene (N-PRa-KO) using a Nestin promoter/enhancer driven Cre recombi_x0002_nase and examined forebrain development. The expression of PDGFRa was efficiently suppressed in the Olig2+cells in N-PRa-KO mice. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We established a con_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ditional knockout Mouse for the Pdgfra gene (N-PRa-KO) using a Nestin promoter/enhancer driven Cre recombi_x0002_nase and examined forebrain development. The expression of PDGFRa was efficiently suppressed in the Olig2+cells in N-PRa-KO mice. Immunohistochemical staining We established a con_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ditional knockout Mouse for the Pdgfra gene (N-PRa-KO) using a Nestin promoter/enhancer driven Cre recombi_x0002_nase and examined forebrain development. The expression of PDGFRa was efficiently suppressed in the Olig2+cells in N-PRa-KO mice. PCR，Immunostainings Pdgfra We established a con_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ditional knockout Mouse for the Pdgfra gene (N-PRa-KO) using a Nestin promoter/enhancer driven Cre recombi_x0002_nase and examined forebrain development. The expression of PDGFRa was efficiently suppressed in the Olig2+cells in N-PRa-KO mice. 32277945 chr5 51380781 51382781 ISL1 Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. human aortic High+Lowthroughput Statin downregulation of miR-652-3p protects endothelium from dyslipidemia by promoting ISL1 expression 不相关 Dyslipidemia endothelial cell E_02_0703 qRT-PCR，Western blot Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. Immunohistochemical staining Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. qRT-PCR，Western blot ISL1 Dyslipidemia leads to decreased nitric oxide (NO) bioavailability, an early sign of endothelial failure. Low insulin gene enhancer protein (ISL1) levels decrease healthy NO bioavailability. 32266943 chr18 69473409 69475409 Tcf4 Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation mouse brain High+Lowthroughput Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation 不相关 syndromic and non-syndromic formsof intellectual disability, schizophrenia and autism primary cell E_02_0704 Immunocytochemistry，RT-PCR，Chromatin immunoprecipitation Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation Immunohistochemical staining Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation Immunocytochemistry，RT-PCR，Chromatin immunoprecipitation Tcf4 Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation 32257815 chr13 68705525 68707525 Mtrr Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice mouse liver High+Lowthroughput Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice 不相关 Nonalcoholic fatty liver disease hepatocyte E_02_0705 RT-qPCR Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice Immunohistochemical staining Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice RT-qPCR Mtrr Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice 32256588 chr16 72102792 72104792 Robo1 We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. mouse High+Lowthroughput Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma 不相关 Head and neck squamous cell carcinoma Head and Neck Squamous Cell E_02_0706 real-time PCR，Western blot， flow cytometry We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. Immunohistochemical staining We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. real-time PCR，Western blot， flow cytometry Robo1 We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. 32245889 chr19 49672950 49674950 PRMT1 Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. human liver High+Lowthroughput The polymorphism rs975484 in the protein arginine methyltransferase 1 gene modulates expression of immune checkpoint genes in hepatocellular carcinoma 相关 rs975484 hepatocellular carcinoma programmed cell E_02_0707 Real Time PCR，Immunohistochemistry，ChIP Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. Immunohistochemical staining Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. Real Time PCR，Immunohistochemistry，ChIP PRMT1 Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. 32245184 chr12 71935898 71937898 TPH2 For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the Mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. human High+Lowthroughput The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion 不相关 positive cell E_02_0708 PCR For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the Mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the Mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. Immunohistochemical staining For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the Mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. PCR TPH2 For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the Mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. 32243837 chr12 49016038 49018038 KMT2D KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer human lung tumor High+Lowthroughput KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer 不相关 Lung Cancer Lung cancer cell E_02_0709 RT-PCR，ChIP-seq，RNA-seq KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer Immunohistochemical staining KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer RT-PCR，ChIP-seq，RNA-seq KMT2D KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer 32241909 chr11 94897936 94899936 Samd14 Deletion of a Samd14 enhancer(Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcrip_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tion factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia Mouse model. mouse High+Lowthroughput Sterile α-motif domain requirement for cellular signaling and survival 不相关 precursor cell E_02_0710 Western blotting，flow cytometric Deletion of a Samd14 enhancer(Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcrip_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tion factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia Mouse model. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Deletion of a Samd14 enhancer(Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcrip_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tion factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia Mouse model. Immunohistochemical staining Deletion of a Samd14 enhancer(Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcrip_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tion factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia Mouse model. Western blotting，flow cytometric Samd14 Deletion of a Samd14 enhancer(Samd14–Enh), occupied by GATA2 and SCL/TAL1 transcrip_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tion factors, reduces SAMD14 expression in bone marrow and spleen and is lethal in a hemolytic anemia Mouse model. 32359406 chr22 41364688 41366688 TEF We show that Lox interacts with, and directly oxidizes, vestigial-like 3 (Vgll3), a transcriptional co-activator acting with Mef2 and transcriptional enhancer factor (TEF) TFs. human parenchymal High+Lowthroughput Intracellular Role for the Matrix-Modifying Enzyme Lox in Regulating Transcription Factor Subcellular Localization and Activity in Muscle Regeneration 不相关 progenitor cell E_02_0711 Western Blot,Real-time Quantitative PCR,Immunofluorescent Staining We show that Lox interacts with, and directly oxidizes, vestigial-like 3 (Vgll3), a transcriptional co-activator acting with Mef2 and transcriptional enhancer factor (TEF) TFs. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that Lox interacts with, and directly oxidizes, vestigial-like 3 (Vgll3), a transcriptional co-activator acting with Mef2 and transcriptional enhancer factor (TEF) TFs. Immunohistochemical staining We show that Lox interacts with, and directly oxidizes, vestigial-like 3 (Vgll3), a transcriptional co-activator acting with Mef2 and transcriptional enhancer factor (TEF) TFs. Western Blot,Real-time Quantitative PCR,Immunofluorescent Staining TEF We show that Lox interacts with, and directly oxidizes, vestigial-like 3 (Vgll3), a transcriptional co-activator acting with Mef2 and transcriptional enhancer factor (TEF) TFs. 32691553 chr4 108045150 108047150 LEF1 The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results,we screened the probable key odontogenic genes. human mesenchymal High+Lowthroughput [Screen and Function Study of the Key Regulative Odontogenic Genes in Mice] 不相关 epithelial cell E_02_0712 RT-qPCR, immunohistochemistry staining The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results,we screened the probable key odontogenic genes. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results,we screened the probable key odontogenic genes. Immunohistochemical staining The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results,we screened the probable key odontogenic genes. RT-qPCR, immunohistochemistry staining LEF1 The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results,we screened the probable key odontogenic genes. 32680543 chr16 67559370 67561370 CTCF Sex-difer_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. human liver High+Lowthroughput Impact of 3D genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in Mouse liver 不相关 embryonic stem cell E_02_0713 PCR，ChIP‑seq Sex-difer_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Sex-difer_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. Immunohistochemical staining Sex-difer_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. PCR，ChIP‑seq CTCF Sex-difer_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_ential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. 32672536 chr12 114667169 114669169 TBX3 Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction human cardiac conduction High+Lowthroughput Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction 不相关 stem cell，primary cultured cell E_02_0714 STARR-seq,ATAC-seq Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction Immunohistochemical staining Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction STARR-seq,ATAC-seq TBX3 Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction 32671756 chr1 156460926 156462926 MEF2D Myocyte enhancer factor 2D(MEF2D) is an important protein for neuron survival, and it can be degraded by CMA. human brain High+Lowthroughput Autophagy and Tumour Stem Cells 相关 Cancer stem cell E_02_0715 Myocyte enhancer factor 2D(MEF2D) is an important protein for neuron survival, and it can be degraded by CMA. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Myocyte enhancer factor 2D(MEF2D) is an important protein for neuron survival, and it can be degraded by CMA. Immunohistochemical staining Myocyte enhancer factor 2D(MEF2D) is an important protein for neuron survival, and it can be degraded by CMA. MEF2D Myocyte enhancer factor 2D(MEF2D) is an important protein for neuron survival, and it can be degraded by CMA. 32669659 chr19 16322430 16324430 KLF2 Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). human aortic High+Lowthroughput The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis 不相关 atherosclerosis endothelial cell E_02_0716 Q-PCR,RT‑PCR,Immunohistochemical analysis Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Immunohistochemical staining Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Q-PCR,RT‑PCR,Immunohistochemical analysis KLF2 Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). 32669118 chr18 33575219 33577219 ASXL3 ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer human cancer High+Lowthroughput ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer 不相关 small cell lung cancer SCLC cell E_02_0717 Immunoprecipitation,real-time PCR,ChIP-seq,RNA-seq ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer Immunohistochemical staining ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer Immunoprecipitation,real-time PCR,ChIP-seq,RNA-seq ASXL3,BRD4,BAP1 ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer;ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer;ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer 32667910 chr12 85517961 85519961 Fos Our findings reveal that 533 genes, including known contractility-driving genes(Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2],Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are up_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_regulated at day 19 during active labor because of an increase in transcription at gene bod_x0002_ies. mouse myometrial High+Lowthroughput The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice 不相关 smooth muscle cell E_02_0718 RNA-seq,RT-qPCR Our findings reveal that 533 genes, including known contractility-driving genes(Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2],Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are up_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_regulated at day 19 during active labor because of an increase in transcription at gene bod_x0002_ies. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Our findings reveal that 533 genes, including known contractility-driving genes(Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2],Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are up_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_regulated at day 19 during active labor because of an increase in transcription at gene bod_x0002_ies. Immunohistochemical staining Our findings reveal that 533 genes, including known contractility-driving genes(Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2],Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are up_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_regulated at day 19 during active labor because of an increase in transcription at gene bod_x0002_ies. RNA-seq,RT-qPCR Fos Our findings reveal that 533 genes, including known contractility-driving genes(Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2],Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are up_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_regulated at day 19 during active labor because of an increase in transcription at gene bod_x0002_ies. 32664627 chr22 41364474 41366474 TEF Chagas heart disease; heart endothelial cells; hippo signaling; transcriptional enhancer factor (TEF) family/TEA domain (TEAD) family. human High+Lowthroughput Thrombospondin-1 Plays an Essential Role in Yes-Associated Protein Nuclear Translocation during the Early Phase of Trypanosoma cruzi Infection in Heart Endothelial Cells 不相关 Trypanosoma cruzi Infection cardiac endothelial cell E_02_0719 Immunoblotting, Immunofluorescence Chagas heart disease; heart endothelial cells; hippo signaling; transcriptional enhancer factor (TEF) family/TEA domain (TEAD) family. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Chagas heart disease; heart endothelial cells; hippo signaling; transcriptional enhancer factor (TEF) family/TEA domain (TEAD) family. Immunohistochemical staining Chagas heart disease; heart endothelial cells; hippo signaling; transcriptional enhancer factor (TEF) family/TEA domain (TEAD) family. Immunoblotting, Immunofluorescence TEF Chagas heart disease; heart endothelial cells; hippo signaling; transcriptional enhancer factor (TEF) family/TEA domain (TEAD) family. 32661061 chr1 45337174 45339174 TOE1 We show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT. human vascular High+Lowthroughput Photoexcited Cryptochrome2 Interacts Directly with TOE1 and TOE2 in Flowering Regulation 不相关 E_02_0720 Western Blotting,RT-qPCR,ChIP-qPCR We show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT. Immunohistochemical staining We show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT. Western Blotting,RT-qPCR,ChIP-qPCR TOE1,CRY2 We show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT.;We show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT. 32661056 chr7 148804103 148806103 EZH2 EZH2 emerged as the predominant driver of the differentially downregulated genes. We suggest that functional gene alterations identified in metabolism, transcription and intercellular communication underlie critical microglial heterogeneity and sex differences in CNS regions that contribute to respiratory disorders categorized by dysfunction in neural control. human High+Lowthroughput Sex- and Region-Specific Differences in the Transcriptomes of Rat Microglia from the Brainstem and Cervical Spinal Cord 不相关 Immune cell E_02_0721 RNA Sequencing， EZH2 emerged as the predominant driver of the differentially downregulated genes. We suggest that functional gene alterations identified in metabolism, transcription and intercellular communication underlie critical microglial heterogeneity and sex differences in CNS regions that contribute to respiratory disorders categorized by dysfunction in neural control. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq EZH2 emerged as the predominant driver of the differentially downregulated genes. We suggest that functional gene alterations identified in metabolism, transcription and intercellular communication underlie critical microglial heterogeneity and sex differences in CNS regions that contribute to respiratory disorders categorized by dysfunction in neural control. Immunohistochemical staining EZH2 emerged as the predominant driver of the differentially downregulated genes. We suggest that functional gene alterations identified in metabolism, transcription and intercellular communication underlie critical microglial heterogeneity and sex differences in CNS regions that contribute to respiratory disorders categorized by dysfunction in neural control. RNA Sequencing， EZH2 EZH2 emerged as the predominant driver of the differentially downregulated genes. We suggest that functional gene alterations identified in metabolism, transcription and intercellular communication underlie critical microglial heterogeneity and sex differences in CNS regions that contribute to respiratory disorders categorized by dysfunction in neural control. 32657640 chr7 37903134 37905134 SFRP4 SFRP4 overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. human adipose High+Lowthroughput Effects of SFRP4 overexpression on the production of adipokines in transgenic mice 不相关 obesity mesenchymal stem cell E_02_0722 qPCR,western blotting SFRP4 overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq SFRP4 overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. Immunohistochemical staining SFRP4 overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. qPCR,western blotting SFRP4 SFRP4 overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. 32647123 chr6 125070535 125072535 Chd4 Conditional knockout of Chd4 promotes recruitment of the archi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tectural protein complex cohesin preferentially to gene enhancers in granule neurons in vivo. mouse High+Lowthroughput The chromatin remodeling enzyme Chd4 regulates genome architecture in the Mouse brain 不相关 embryonic stem cell E_02_0723 DNaseI-seq,ChIP-seq,RNA-seq Conditional knockout of Chd4 promotes recruitment of the archi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tectural protein complex cohesin preferentially to gene enhancers in granule neurons in vivo. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Conditional knockout of Chd4 promotes recruitment of the archi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tectural protein complex cohesin preferentially to gene enhancers in granule neurons in vivo. Immunohistochemical staining Conditional knockout of Chd4 promotes recruitment of the archi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tectural protein complex cohesin preferentially to gene enhancers in granule neurons in vivo. DNaseI-seq,ChIP-seq,RNA-seq Chd4 Conditional knockout of Chd4 promotes recruitment of the archi_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x005f_x0002_tectural protein complex cohesin preferentially to gene enhancers in granule neurons in vivo. 33084203 chr2 147881950 147883950 Foxa2 We established a Foxa2 notochord_x005f_x0002_specific enhancer-driven Cre transgenic Mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). mouse High+Lowthroughput Transformation of resident notochord-descendent nucleus pulposus cells in Mouse injury-induced fibrotic intervertebral discs 不相关 E_02_0724 We established a Foxa2 notochord_x005f_x0002_specific enhancer-driven Cre transgenic Mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We established a Foxa2 notochord_x005f_x0002_specific enhancer-driven Cre transgenic Mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). Immunohistochemical staining We established a Foxa2 notochord_x005f_x0002_specific enhancer-driven Cre transgenic Mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). Foxa2 We established a Foxa2 notochord_x005f_x0002_specific enhancer-driven Cre transgenic Mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). 33065764 chr15 38485286 38487286 RASGRP1 By analyzing H3K27 acetylation profiles in Human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity_x005f_x0002_associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. human High+Lowthroughput Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity 不相关 inflammatory disease T cell E_02_0725 Flow cytometry By analyzing H3K27 acetylation profiles in Human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity_x005f_x0002_associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq By analyzing H3K27 acetylation profiles in Human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity_x005f_x0002_associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. Immunohistochemical staining By analyzing H3K27 acetylation profiles in Human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity_x005f_x0002_associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. Flow cytometry RASGRP1 By analyzing H3K27 acetylation profiles in Human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity_x005f_x0002_associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. 33060580 chr3 181709320 181711320 SOX2 We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural pro_x005f_x0002_genitors. human High+Lowthroughput DOT1L-mediated murine neuronal differentiation associates with H3K79me2 accumulation and preserves SOX2-enhancer accessibility 不相关 embryonic stem cell E_02_0726 ChIP-seq,RNA-seq,ATAC-seq,Immunoblotting We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural pro_x005f_x0002_genitors. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural pro_x005f_x0002_genitors. Immunohistochemical staining We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural pro_x005f_x0002_genitors. ChIP-seq,RNA-seq,ATAC-seq,Immunoblotting SOX2 We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural pro_x005f_x0002_genitors. 33054400 chr2 150520026 150522026 Vsx1 We identify the enhancers that are sufficient to drive the spatially restricted expression of the Vsx1 and Rx genes in the OPC. mouse High+Lowthroughput Identification of enhancers that drive the spatially restricted expression of Vsx1 and Rx in the outer proliferation center of the developing Drosophila optic lobe 不相关 stem cell E_02_0727 PCR,Immunohistochemistry We identify the enhancers that are sufficient to drive the spatially restricted expression of the Vsx1 and Rx genes in the OPC. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We identify the enhancers that are sufficient to drive the spatially restricted expression of the Vsx1 and Rx genes in the OPC. Immunohistochemical staining We identify the enhancers that are sufficient to drive the spatially restricted expression of the Vsx1 and Rx genes in the OPC. PCR,Immunohistochemistry Vsx1 We identify the enhancers that are sufficient to drive the spatially restricted expression of the Vsx1 and Rx genes in the OPC. 33044128 chr13 116432461 116434461 Isl1 ATAC-seq Reveals an Isl1 Enhancer that Regulates Sinoatrial Node Development and Function mouse High+Lowthroughput ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function 不相关 Cardiac pacemaker cell E_02_0728 ATAC-seq ATAC-seq Reveals an Isl1 Enhancer that Regulates Sinoatrial Node Development and Function Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq ATAC-seq Reveals an Isl1 Enhancer that Regulates Sinoatrial Node Development and Function Immunohistochemical staining ATAC-seq Reveals an Isl1 Enhancer that Regulates Sinoatrial Node Development and Function ATAC-seq Isl1 ATAC-seq Reveals an Isl1 Enhancer that Regulates Sinoatrial Node Development and Function 33040635 chr12 114667368 114669368 TBX3 Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer human atrial High+Lowthroughput Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer 相关 rs61928421 pacemaker cell E_02_0729 qPCR Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer Immunohistochemical staining Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer qPCR TBX3 Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer 33033216 chr10 102827537 102829537 CYP17A1 Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. human ovarian High+Lowthroughput The mole genome reveals regulatory rearrangements associated with adaptive intersexuality 不相关 germ line cell E_02_0730 Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Immunohistochemical staining Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. CYP17A1 Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. 33033055 chr12 49016308 49018308 KMT2D Trithorax-related (trr), MLL3 (KMT2C), and MLL4 (KMT2D) represent the “branch” of COMPASS family ly_x005f_x0002_sine methyltransferases responsible for catalyzing histone 3 lysine 4 monomethylation (H3K4me1) at enhancer chro_x0002_matin in Drosophila and mammals, respectively (Herzet al. 2012; Hu et al. 2013). human High+Lowthroughput A small UTX stabilization domain of Trr is conserved within mammalian MLL3-4/COMPASS and is sufficient to rescue loss of viability in null animals 不相关 embryonic stem cell E_02_0731 Western blots,chip-seq Trithorax-related (trr), MLL3 (KMT2C), and MLL4 (KMT2D) represent the “branch” of COMPASS family ly_x005f_x0002_sine methyltransferases responsible for catalyzing histone 3 lysine 4 monomethylation (H3K4me1) at enhancer chro_x0002_matin in Drosophila and mammals, respectively (Herzet al. 2012; Hu et al. 2013). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Trithorax-related (trr), MLL3 (KMT2C), and MLL4 (KMT2D) represent the “branch” of COMPASS family ly_x005f_x0002_sine methyltransferases responsible for catalyzing histone 3 lysine 4 monomethylation (H3K4me1) at enhancer chro_x0002_matin in Drosophila and mammals, respectively (Herzet al. 2012; Hu et al. 2013). Immunohistochemical staining Trithorax-related (trr), MLL3 (KMT2C), and MLL4 (KMT2D) represent the “branch” of COMPASS family ly_x005f_x0002_sine methyltransferases responsible for catalyzing histone 3 lysine 4 monomethylation (H3K4me1) at enhancer chro_x0002_matin in Drosophila and mammals, respectively (Herzet al. 2012; Hu et al. 2013). Western blots,chip-seq KMT2D Trithorax-related (trr), MLL3 (KMT2C), and MLL4 (KMT2D) represent the “branch” of COMPASS family ly_x005f_x0002_sine methyltransferases responsible for catalyzing histone 3 lysine 4 monomethylation (H3K4me1) at enhancer chro_x0002_matin in Drosophila and mammals, respectively (Herzet al. 2012; Hu et al. 2013). 33028869 chr6 31572563 31574563 TNF Further bioinformatic analysis, employing Ingenuity Pathway Analysis identifed signifcant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identifed a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic diferentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation. human High+Lowthroughput Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of Human skeletal (mesenchymal) stem cells 不相关 stem cell E_02_0732 qRT-PCR Further bioinformatic analysis, employing Ingenuity Pathway Analysis identifed signifcant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identifed a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic diferentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Further bioinformatic analysis, employing Ingenuity Pathway Analysis identifed signifcant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identifed a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic diferentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation. Immunohistochemical staining Further bioinformatic analysis, employing Ingenuity Pathway Analysis identifed signifcant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identifed a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic diferentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation. qRT-PCR TNF Further bioinformatic analysis, employing Ingenuity Pathway Analysis identifed signifcant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identifed a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic diferentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation. 33026112 chr7 148804775 148806775 EZH2 Chromatin immunoprecipitation and dual_x005f_x0002_luciferase assays validated that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibited transcription of miR-22 promoter human High+Lowthroughput Inhibition of EZH2 attenuates coronary heart disease by interacting with microRNA-22 to regulate the TXNIP/nuclear factor-κB pathway 不相关 coronary heart disease blood vessel smooth muscle cell E_02_0733 Flow cytometry,RT-PCR Chromatin immunoprecipitation and dual_x005f_x0002_luciferase assays validated that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibited transcription of miR-22 promoter Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Chromatin immunoprecipitation and dual_x005f_x0002_luciferase assays validated that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibited transcription of miR-22 promoter Immunohistochemical staining Chromatin immunoprecipitation and dual_x005f_x0002_luciferase assays validated that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibited transcription of miR-22 promoter Flow cytometry,RT-PCR EZH2 Chromatin immunoprecipitation and dual_x005f_x0002_luciferase assays validated that enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibited transcription of miR-22 promoter 32206101 chr19 10868773 10870773 CARM1 : CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment human mammary cancer High+Lowthroughput A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor α-dependent transcriptional activation and breast carcinogenesis 否 mammary cancer breast cancer cell E_02_0734 Transfection, RT qPCR, Western blot : CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq : CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment Immunohistochemical staining : CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment 转染，RT-qPCR，Western blot CARM1 : CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment 32194081 chr7 148804808 148806808 EZH2 Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. human Colon adenocarcinoma High+Lowthroughput EZH2 inhibition promotes ANGPTL4/CREB1 to suppress the progression of ulcerative colitis Ulcerative colitis E_02_0735 Flow cytometry, RT qPCR, Western blot, ELISA Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. Immunohistochemical staining Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. 流式细胞术，RT-qPCR,western blot,酶联免疫吸附 EZH2 Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. 32218434 chr17 35869035 35871035 CCL5 the prox_x0002_imal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. human Spleen, lymph nodes High+Lowthroughput Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity 否 antitumor immunity T cell E_02_0736 NK cytotoxicity assay, mouse modeling, chromatin immunoprecipitation assay the prox_x0002_imal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq the prox_x0002_imal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. Immunohistochemical staining the prox_x0002_imal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. NK 细胞毒性测定，小鼠造模，染色质免疫沉淀测定 CCL5 the prox_x0002_imal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. 32209973 chr15 99562591 99564591 MEF2A we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function human hypothalamus High+Lowthroughput Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons 否 mitochondrial disorder E_02_0737 Transfection, Western blot, immunofluorescence, cell viability assays we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function Immunohistochemical staining we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function 转染，Western blot，免疫荧光，细胞活力检测 MEF2A we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function 32165301 chr16 69561943 69563943 NFAT5 The nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor that regulates osmoadaptive response in multiple tissues and is highly ex_x0002_pressed in the developing central nervous system. human adrenal gland High+Lowthroughput DDC expression is not regulated by NFAT5 (TonEBP) in dopaminergic neural cell lines 否 Psychiatric disorders E_02_0738 Trt-qpcr, immunohistochemistry, transfection The nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor that regulates osmoadaptive response in multiple tissues and is highly ex_x0002_pressed in the developing central nervous system. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq The nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor that regulates osmoadaptive response in multiple tissues and is highly ex_x0002_pressed in the developing central nervous system. Immunohistochemical staining The nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor that regulates osmoadaptive response in multiple tissues and is highly ex_x0002_pressed in the developing central nervous system. TRT-QPCR，免疫组化，转染 NFAT5 The nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor that regulates osmoadaptive response in multiple tissues and is highly ex_x0002_pressed in the developing central nervous system. 32151973 chr4 88723288 88725288 FAM13A Member A (FAM13A) has been associated with lipid levels and fat mass by genome-wide association studies (GWAS). human Fat High+Lowthroughput FAM13A Represses AMPK Activity and Regulates Hepatic Glucose and Lipid Metabolism 是 rs2276936 Obesity E_02_0739 Western blot，RT-QPCR Member A (FAM13A) has been associated with lipid levels and fat mass by genome-wide association studies (GWAS). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Member A (FAM13A) has been associated with lipid levels and fat mass by genome-wide association studies (GWAS). Immunohistochemical staining Member A (FAM13A) has been associated with lipid levels and fat mass by genome-wide association studies (GWAS). Western blot，RT-QPCR FAM13A Member A (FAM13A) has been associated with lipid levels and fat mass by genome-wide association studies (GWAS). 32132110 chr5 88714434 88716434 MEF2C g. Further, we identified the Myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain-of-function significantly deterred cancer-induced muscle wasting and dysfunction in a pre-clinical model of pancreatic ductal adenocarcinoma (PDAC). human colon High+Lowthroughput MEF2c-dependent downregulation of Myocilin mediates cancer-induced muscle wasting and associates with cachexia in cancer patients 否 Muscle wasting E_02_0740 Immunohistochemistry, oil red O staining, Western blot, RT-qPCR g. Further, we identified the Myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain-of-function significantly deterred cancer-induced muscle wasting and dysfunction in a pre-clinical model of pancreatic ductal adenocarcinoma (PDAC). Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq g. Further, we identified the Myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain-of-function significantly deterred cancer-induced muscle wasting and dysfunction in a pre-clinical model of pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical staining g. Further, we identified the Myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain-of-function significantly deterred cancer-induced muscle wasting and dysfunction in a pre-clinical model of pancreatic ductal adenocarcinoma (PDAC). 免疫组化，油红O染色，Western blot，RT-QPCR MEF2C g. Further, we identified the Myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain-of-function significantly deterred cancer-induced muscle wasting and dysfunction in a pre-clinical model of pancreatic ductal adenocarcinoma (PDAC). 32130892 chr5 158693087 158695087 EBF1 Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. human Fat High+Lowthroughput Early B Cell Factor Activity Controls Developmental and Adaptive Thermogenic Gene Programming in Adipocytes 否 Obesity E_02_0741 He staining, Western blot, RT-qPCR, chip seq Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. Immunohistochemical staining Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. HE染色，Western blot，RT-QPCR，ChIP-seq EBF1 Enhancer profiling and genetic assays identified EBF1 as a candidate regulator of the cold response in BAT. 32068311 chr8 11674018 11676018 GATA4 We have also used the G2 enhancer of the GATA4 gene as a driver due to its activation in the proepicardium. human heart High+Lowthroughput Epicardial cell lineages and the origin of the coronary endothelium 否 coronary artery disease E_02_0742 Immunohistochemistry, flow cytometry, confocal, We have also used the G2 enhancer of the GATA4 gene as a driver due to its activation in the proepicardium. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq We have also used the G2 enhancer of the GATA4 gene as a driver due to its activation in the proepicardium. Immunohistochemical staining We have also used the G2 enhancer of the GATA4 gene as a driver due to its activation in the proepicardium. 免疫组化，流式细胞术，共聚焦， GATA4 We have also used the G2 enhancer of the GATA4 gene as a driver due to its activation in the proepicardium. 32035085 chr10 30705715 30707715 Hey2 A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart mouse heart High+Lowthroughput Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors 否 Heart disease E_02_0743 Chip SEQ, transfection, immunohistochemistry, in situ hybridization, RT-qPCR, luciferase reporter assay A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart Immunohistochemical staining A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart ChIP-seq，转染，免疫组化，原位杂交，RT-QPCR，荧光素酶报告测定 Hey2 A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart 32029739 chr8 127791613 127793613 PVT1 However, the function of PVT1 intragenic enhancers in BETi-resistant leukemia cells remains lar_x0002_gely unexplored. human blood High+Lowthroughput A combination strategy targeting enhancer plasticity exerts synergistic lethality against BETi-resistant leukemia cells 否 leukemia E_02_0744 Western blot, transfection, RT-qPCR, chip, ALT assay, flow cytometry However, the function of PVT1 intragenic enhancers in BETi-resistant leukemia cells remains lar_x0002_gely unexplored. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq However, the function of PVT1 intragenic enhancers in BETi-resistant leukemia cells remains lar_x0002_gely unexplored. Immunohistochemical staining However, the function of PVT1 intragenic enhancers in BETi-resistant leukemia cells remains lar_x0002_gely unexplored. Western blot，转染，RT-QPCR，ChIP，ALT检测，流式细胞术 PVT1 However, the function of PVT1 intragenic enhancers in BETi-resistant leukemia cells remains lar_x0002_gely unexplored. 32025238 chr11 89321560 89323560 NOX4 NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce pre_x0002_mature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence human bone marrow High+Lowthroughput A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration 否 Disc pathologies E_02_0745 SA- β- Gal staining, edu staining, transfection, Western blot, immunofluorescence, immunohistochemistry, RT-qPCR, ROS measurement, flow cytometry, chip NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce pre_x0002_mature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce pre_x0002_mature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence Immunohistochemical staining NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce pre_x0002_mature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence SA-β-gal 染色，EDU染色，转染，Western blot，免疫荧光，免疫组化，RT-QPCR,ROS 测量,流式细胞术，ChIP NOX4 NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce pre_x0002_mature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence 32022326 chr7 148804929 148806929 EZH2 Chip-seq demonstrated binding of β-catenin to the promoter of EZH2, a key component of the PRC2 complex that catalyzes histone methylation. human bone marrow High+Lowthroughput β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2 否 Bone marrow disorders mesenchymal stem cell of the bone marrow E_02_0746 Immunofluorescence, oil red O staining, RT-qPCR, Western blot, chip Chip-seq demonstrated binding of β-catenin to the promoter of EZH2, a key component of the PRC2 complex that catalyzes histone methylation. Enhancer qRT-PCR,qPCR,ChIP,3C RNA-Seq Chip-seq demonstrated binding of β-catenin to the promoter of EZH2, a key component of the PRC2 complex that catalyzes histone methylation. Immunohistochemical staining Chip-seq demonstrated binding of β-catenin to the promoter of EZH2, a key component of the PRC2 complex that catalyzes histone methylation. 免疫荧光，油红O染色，RT-QPCR，Western blot，CHIP EZH2 Chip-seq demonstrated binding of β-catenin to the promoter of EZH2, a key component of the PRC2 complex that catalyzes histone methylation. 30590035 chr6 31139519 31140167 TFAP2C From this screen, we used CRISPR/Cas9 approaches to determine that re-opening of a large fraction of TFAP2C-bound ground-state naive enhancers (NEs) combined with a shift in the global transcriptional program toward ground-state naive pluripotency is a major milestone in the regeneration of human germline cells from primed pluripotent stem cells. human embryonic Low+High throughput The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation -- primordial germ cell E_02_0747 ATAC-seq,ChIP-seq These data show that the PE, DE, and NE are all open in hPGCLCs at day 4 of aggregate differentiation, with the NE being more open in hPGCs than the DE and PE. This observation raises the possibility that restriction of OCT4 expression between days 2 and 3 of aggregate differentiation may be due to NE and/or the DE enhancer activation at the OCT4 locus. Given that the NE is bound by TFAP2C in groundstate naive pluripotent stem cells, whereas the DE is not , we next confirmed that the OCT4 NE is also a target of TFAP2C during hPGCLC differentiation. Enhancer -- ChIP-qPCR OCT3, OCT4, OTF-3, OTF3, OTF4, Oct-3, Oct-4 TFAP2C regulates human germline cell formation is opening naive-specific Enhancers, with one of these Enhancers corresponding to the NE at the OCT4 locus. CRISPR/Cas9 Using CRISPR/Cas9, we show that deleting the TFAP2C-bound naive enhancer at the OCT4 locus (also called POU5F1) results in impaired OCT4 expression and a negative effect on hPGCLC identity. AP2-GAMMA,ERF1,TFAP2G,hAP-2g CRISPR/Cas9 -- -- POU5F1 TFAP2C Screenshot of ATAC-seq and TFAP2C ChIP-seq signals showing three Enhancers at the POU5F1 locus (encoding OCT4). Shaded boxes highlight the naive Enhancer(NE),proximalEnhancer(PE),anddistalEnhancer(DE)atthePOU5F1locus.DEdeletion andNEdeletion indicategenomicregionsthatweredeleted by CRISPR/Cas9-mediated genome editing. Primers for ChIP-qPCR (P1-2,P3-4,P5-6) of NE and control regions are shown. Using CRISPR/Cas9, we show that deleting the TFAP2C-bound naive Enhancer at the OCT4 locus (also called POU5F1) results in impaired OCT4 expression and a negative effect on hPGCLC identity. 30568279 chr14 106327635 106328903 IGHE As proof-of-concept that HiDRA is capable of identifying true enhancer elements, we examined the well-studied immunoglobulin heavy-chain enhancer within the intron of the immunoglobulin heavy constant epsilon (IGHE) gene human lymph Low+High throughput High-resolution genome-wide functional dissection of transcriptional regulatory regions and nucleotides in human -- GM12878 cell E_02_0748 Luciferase Reporter Assay,ChIP-seq Surprisingly, this enrichment stayed constant thereafter for promoter regions, and increased modestly for enhancer regions, ultimately surpassing the enrichment seen for promoters. In fact, even though promoter chromatin states were more enriched at intermediate HiDRA activity levels,enhancer chromatin states were the most enriched at the highest HiDRA activity levels , suggesting that enhancer elements have a greater dynamic range of regulatory activity potential, which has implications for the regulatory architecture of genes. Enhancer -- Luciferase Reporter Assay IgE -- -- -- -- -- -- -- IGHE -- We observed that the peak of HiDRA activity is centered precisely within the region previously identi?ed as driving Enhancer activity in low-throughput luciferase assays (Fig. 2c). -- 30566872 chr10 33492690 33519530 TF The transcription factor (TF) p63 is an ancient member of the p53 gene family. human skin Low+High throughput Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape EEC syndrome Epidermal cell E_02_0749 siRNA,ChIP-seq Two clusters of active enhancers were bound by p63 . Regions in C3 showed higher p63-binding signals.nearby genes were involved in apoptosis and epidermis development. Regions in C4 had relatively lower p63-binding signals, and nearby genes were involved in keratinocyte differentiation. Enhancer -- siRNA BDCA4,CD304,NP1,NRP,VEGF165R -- -- -- AIS,B(p51A),B(p51B),EEC3,KET,LMS,NBP,OFC8,RHS,SHFM4,TP53CP,TP53L,TP73L,p40,p51,p53CP,p63,p73H,p73L,AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1, PEBP2aB, PEBP2alpha siRNA,qRT-PCR -- -- NRP1 TP63,RUNX1 Indeed, we observed a clear decrease of H3K27ac signals at Enhancers that had higher H3K27ac signals and bound by RUNX1 in p63 mutant keratinocytes (Figure 6B; n = 6,035) in two biological replicas, such as Enhancers near NRP1, which is involved in angiogenesis . Gene expression analysis by qRT-PCR of TP63 and RUNX1 expression in TP63 knockdown (siTP63) compared to non-targeting siRNA (siNT) in control keratinocytes. 30545847 chr10 50623698 50625698 Mc4r Using obesity as a model, we tested in mice whether CRISPR-mediated activation of the existing normal copy of two different genes, Sim1 or Mc4r, where loss-of-function mutations that lead to haploinsufficiency are a major cause of human obesity, can rescue their obesity phenotype. mouse Low+High throughput CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. 否 Haploinsufficiency Hypothalamus cell E_02_0750 ChIP-seq,ATAC-seq CRISPRa targeting of the Sim1 promoter or its hypothalamusspecific enhancer, which is 270 kilobases away from the gene, in Sim1 haploinsufficient mice increased the expression of the normal copy of Sim1. Enhancer -- ChIP-seq,PCR,Transgenic mice bHLHe14, mSIM1 Transgenic-based CRISPRa targeting of the Sim1 promoter or its distant hypothalamic enhancer up-regulated its expression from the endogenous functional allele in a tissue-specific manner, rescuing the obesity phenotype in Sim1 heterozygous mice. CRISPR/Cas9,ChIP-seq Transgenic-based CRISPRa targeting of the Sim1 promoter or its distant hypothalamic enhancer up-regulated its expression from the endogenous functional allele in a tissue-specific manner, rescuing the obesity phenotype in Sim1 heterozygous mice. bHLHe14,mSIM1 CRISPR/Cas9,qPCR -- -- Sim1,Sim1 Sim1,Sim1 We also carried out ChIP-seq using an antibody against S. pyogenes Cas9 in both CRISPRa-promoter and CRISPRa-Enhancer transfected cells and found on-target binding for the promoter and Enhancer,respectively.;We also carried out ChIP-seq using an antibody against S. pyogenes Cas9 in both CRISPRa-promoter and CRISPRa-Enhancer transfected cells and found on-target binding for the promoter and Enhancer,respectively. CRISPRa targeting of the Sim1 promoter or its hypothalamusspecific enhancer, which is 270 kilobases away from the gene, in Sim1 haploinsufficient mice increased the expression of the normal copy of Sim1. This up-regulation was sufficient to rescue the obesity phenotype of Sim1 heterozygous mice and led to significantly reduced food intake and body fat content in thesemice.;CRISPRa targeting of the Sim1 promoter or its hypothalamusspecific enhancer, which is 270 kilobases away from the gene, in Sim1 haploinsufficient mice increased the expression of the normal copy of Sim1. This up-regulation was sufficient to rescue the obesity phenotype of Sim1 heterozygous mice and led to significantly reduced food intake and body fat content in thesemice. 30527662 chr17 30249928 30278499 CTCF Deletion of CTCF sites at the boundary of select insulated neighborhoods results in ectopic transcription stimulation of one or more flanking genes via formation of an enhancer-promoter loop across the region encompassing the deleted boundary (Dowen et al., 2014). human Low+High throughput Promoter-Enhancer Communication Occurs Primarily within Insulated Neighborhoods 否 -- embryonic stem cell E_02_0751 ChIP-seq,ChIA-PET The data show that the promoters are located within Smc1 ChIA-PET loops,the anchors of which align with strong cohesin and CTCF ChIP-seq peaks lacking H3K27ac ( These insulated neighborhoods encompass the TSS(arrow),promoters (vertical gray bars),and potential Enhancers of Mitf and Sik1 (vertical green bar). View of a genomic region around Mitf integrating Smc1 ChIA-PET,and Smc1,Smc3,Rad21,CTCF,Med1,and H3K27ac ChIP-seq with 4C data and promoter capture Hi-C data. Enhancer 4C Hi-C,ChIP-seq,ChIA-PET Hrt-20,Msk,Sik,Sik-1,Snf1lk -- -- -- Err2,Errb,Estrrb,Nr3b2,AI480703,CRSP210,DRIP205,PBP,Pparbp,TRAP220,TRIP-2,l11Jus15 ChIP,Immobilized Template Assay,siRNA,Western blot -- -- Sik1 Esrrb,Med1 High-resolution 4C was employed using promoter viewpoints to determine whether individual genes fit into the framework described in Figure 1.Figures 2A and 2B compare the Mitf and Sik1 genes expressed at low(RPKM = 2.2) and modest (RPKM = 21) levels, respectively, as measured by mRNA-seq and nascent RNA-seq (RPKM 0.53 and 4.2 for Mitf and Sik1). The data show that the promoters are located within Smc1 ChIA-PET loops, the anchors of which align with strong cohesin and CTCF ChIP-seq peaks (vertical red bars) lacking H3K27ac. Consistent with the biochemical data, knockdown of Esrrb by small interfering RNA (siRNA) (Esrrb KD) in cells causes diminished recruitment of Mediator (Med1 and Med12) to Esrrb binding sites genome-wide.For example, upon Esrrb KD, Med1 and Med12 binding decreases at Esrrb sites within the enhancer (Enh) of the divergently transcribed Slc13a5 and Xaf1 genes.In sum, on select genes, Esrrb KD can be used to deplete the Mediator and inactivate Enhancers, either partially or near fully, to downregulate transcription of their target genes. 30518632 chr1 47704791 47705107 NOTCH3 The two compounds induced apoptosis in TCP-resistant T-ALL cells in vitro and in vivo by repressing transcription of the NOTCH3 and TAL1 genes through increased H3K9 methylation and reciprocal H3K27 deacetylation at superenhancer regions. human nerve Low throughput Eradication of Central Nervous System Leukemia of T-Cell Origin with a Brain-Permeable LSD1 Inhibitor Central Nervous System Leukemia T-acute lymphoblastic leukemia (T-ALL) E_02_0752 ChIP-qPCR,qRT-PCR,ChIP,Transgenic mice We found robust cytotoxicity against T-ALL cells, but not normal bone marrow progenitors, for two N-alkylated TCP derivatives, S2116 and S2157. The two compounds induced apoptosis in TCP-resistant T-ALL cells in vitro and in vivo by repressing transcription of the NOTCH3 and TAL1 genes through increased H3K9 methylation and reciprocal H3K27 deacetylation at super-enhancer regions. Super-Enhancer -- qRT-PCR,ChIP SCL,TCL5,bHLHa17,tal-1 -- -- -- HSPC082,SIP-1,SIP1,SMADIP1,ZFHX1B RT-PCR -- -- TAL1,TAL1,TAL1 ZEB2,ZEB2,ZEB2 we found that both S2116 and S2157 readily increased the methylation level of H3K9 and reciprocally reduced the acetylation level of H3K27 at Super-Enhancer regions of the NOTCH3 and TAL1 genes (GRCh38/hg38: 15,198,031-15,197,862 and GRCh38/hg38: 47,239,435-47,239,119,respectively) using ChIP assays.In addition,global ChIP-seq analyses revealed that the acetylation level of H3K27 was readily decreased by LSD1 inhibition through the entire range of NOTCH3 and TAL1 Enhancers.;we found that both S2116 and S2157 readily increased the methylation level of H3K9 and reciprocally reduced the acetylation level of H3K27 at Super-Enhancer regions of the NOTCH3 and TAL1 genes (GRCh38/hg38: 15,198,031-15,197,862 and GRCh38/hg38: 47,239,435-47,239,119,respectively) using ChIP assays.In addition,global ChIP-seq analyses revealed that the acetylation level of H3K27 was readily decreased by LSD1 inhibition through the entire range of NOTCH3 and TAL1 Enhancers.;we found that both S2116 and S2157 readily increased the methylation level of H3K9 and reciprocally reduced the acetylation level of H3K27 at Super-Enhancer regions of the NOTCH3 and TAL1 genes (GRCh38/hg38: 15,198,031-15,197,862 and GRCh38/hg38: 47,239,435-47,239,119,respectively) using ChIP assays.In addition,global ChIP-seq analyses revealed that the acetylation level of H3K27 was readily decreased by LSD1 inhibition through the entire range of NOTCH3 and TAL1 Enhancers. We used the Expression Assays(Hs01097987 for TAL1, Hs01128537 for NOTCH3, Hs00207691 for ZEB2, and Hs01922876 forGAPDH) and TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA) for real-time quantitative RT-PCR (RQ-PCR).;We used the Expression Assays(Hs01097987 for TAL1, Hs01128537 for NOTCH3, Hs00207691 for ZEB2, and Hs01922876 forGAPDH) and TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA) for real-time quantitative RT-PCR (RQ-PCR).;We used the Expression Assays(Hs01097987 for TAL1, Hs01128537 for NOTCH3, Hs00207691 for ZEB2, and Hs01922876 forGAPDH) and TaqMan Universal PCR Master Mix (Applied Biosystems, Waltham, MA) for real-time quantitative RT-PCR (RQ-PCR). 30511964 chr14 76419740 76421740 TGFB3 Mechanistically, this is due to genomic occupancy of FOXA1 on an upstream enhancer of the TGFB3 gene to directly inhibit its transcription. human prostate Low+High throughput Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression Prostate Cancer LNCaP E_02_0753 ChIP-seq,ChIP-qPCR Analysis of FOXA1 ChIP-seq previously performed in LNCaP cells identified strong FOXA1 binding at an enhancer of approximately 3.7 kb upstream of the TGFB3 gene promoter. Enhancer -- ChIP-qPCR ARVD,ARVD1,LDS5,RNHF,TGF-beta3 -- -- -- HNF3A,TCF3A CRISPR/Cas9 -- -- TGFB3 FOXA1 Analysis of FOXA1 ChIP-seq previously performed in LNCaP cells identified strong FOXA1 binding at an Enhancer of approximately 3.7 kb upstream of the TGFB3 gene promoter.Importantly, qRT-PCR analysis demonstrated that CRISPR-mediated Enhancer deletion in only one-fourth of the cell population was able to substantially restore the transcription of TGFB3 gene, comparing cells transfected with TGFB3-targeting gRNAs to those with control gRNAs. To demonstrate that FOXA1 binding at the upstream Enhancer indeed inhibits TGFB3 gene transcription in vivo, we used a lentiviral CRISPR/Cas9 editing system to delete the Enhancer elements with small guide RNAs.Taken together, these results strongly support that FOXA1 binds to an upstream Enhancer to directly repress TGFB3 transcription. 30397001 chr2 234665349 234665739 CCAR1 We demonstrated that CCAR1 can act as an enhancer-dependent coactivator of CAR. human liver Low throughput Cell Cycle and Apoptosis Regulator 1, CCAR1, Regulates Enhancer-Dependent Nuclear Receptor CAR Transactivation. Hepatocellular Carcinoma Hep G2 cell E_02_0754 Luciferase Reporter Assay,qRT-PCR These observations suggested that a specific enhancer region, such as neighboring transcriptional factors, is required for CAR/CCAR1 interaction. Enhancer -- ChIP BILIQTL1,GNT1,HUG-BR1,UDPGT,UDPGT1-1,UGT1,UGT1A CCAR1 enhances transcriptional activity of CAR and acts as an Enhancer-dependent selective cofactor of CAR for UGT1A1 expression. Luciferase Reporter Assay The phenobarbital-responsive Enhancer module of UGT1A1 (gtPBREM)-driven luciferase reporter plasmid (gtPBREM-Luc.) containing a 290-bp distal Enhancer module (-23570/-23180) was constructed based on pGL3-promoter (Promega). CCAR1 ChIP -- -- UGT1A1 CCAR1 The phenobarbital-responsive Enhancer module of UGT1A1 (gtPBREM)-driven Luciferaseplasmid (gtPBREM-Luc.) containing a 290-bp distal Enhancer module (23570/23180) was constructed based on pGL3-promoter (Promega). CCAR1 regulates CAR-mediated mRNA expression (Figs. 4 and 5) and reporter activity (Figs. 2 and 3) of UGT1A1 but not CYP2B6.We speculated that CCAR1 is differentially recruited to CAR-responsive Enhancer regions. To investigate this hypothesis,we carried out ChIP experiments in HepTR/CAR cells. 30008200 chr13 56243248 56243833 CTCF Furthermore, reduced Neurog1 gene expression by CTCF knockdown was found to be associated with changes in histone modification at the gene’s promoter, as well as its upstream enhancer human Low throughput CTCF Regulates Otic Neurogenesis via Histone Modification in the Neurog1Locus 否 -- P19 E_02_0755 ChIP In control cells, the enrichment of H3K27Ac, an active Enhancer marker, was significantly increased at the Neurog1 promoter, as well as other Enhancers, upon RA treatment. Enhancer -- ChIP-qPCR AKA,Math4C,Neurod3,bHLHa6,ngn1 -- -- -- AW108038 ChIP-qPCR -- -- Neurog1 Ctcf Genome-wide CTCF occupancy patterns, which have been mapped across more than 100 mammalian cell types, re_x0002_vealed prominent CTCF binding to the -14.4 kb and -7.6 kb transcription start sites of Neurog1.We performed ChIP-qPCR analysis to validate the in vivo binding of CTCF in P19 cells, and observed strong occupancy of CTCF to these binding sites. Genome-wide CTCF occupancy patterns, which have been mapped across more than 100 mammalian cell types, re_x0002_vealed prominent CTCF binding to the -14.4 kb and -7.6 kb transcription start sites of Neurog1.We performed ChIP-qPCR analysis to validate the in vivo binding of CTCF in P19 cells, and observed strong occupancy of CTCF to these binding sites. 29912188 chr12 132285987 132290767 CTCF This set of genes should include housekeeping genes, such as CTCF or GAPDH. human tumour Low+High throughput Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines 否 -- Ishikawa cell E_02_0756 ChIP-seq Ensure that each regulatory element to be targeted with Enhancer-i has at least 4 unique oligonucleotides designed for it. Order these sequences along with the “U6_internal” primers Enhancer CRISPR/Cas9 -- MMP-17,MT4-MMP,MT4MMP,MTMMP4 -- -- -- -- -- -- -- MMP17,MMP17 --,-- To determine the contributions of ER-bound Enhancers near the estrogen_x0002_regulated gene MMP17,which has 3 binding sites nearby as defined by ChIP-seq.Figure 2D shows results from an Enhancer dissection experiment, where multiple Enhancers nearby MMP17 are targeted alone and in combination using Enhancer-i.;To determine the contributions of ER-bound Enhancers near the estrogen_x0002_regulated gene MMP17,which has 3 binding sites nearby as defined by ChIP-seq.Figure 2D shows results from an Enhancer dissection experiment, where multiple Enhancers nearby MMP17 are targeted alone and in combination using Enhancer-i. --;-- 29628309 chr3 150450617 150456921 JMJD6 JMJD6 Licenses ERa-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex. human breast Low+High throughput JMJD6 Licenses ERa-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex 否 Breast Cancer MCF-7 cell E_02_0757 ChIP-seq,ChIP-qPCR We next assessed whether those estrogen-induced JMJD6 binding sites shared enhancer characteristics, including highly enriched H3K4me1/2 but low levels of H3K4me3. Heatmap and tag density plots confirmed they were, indeed, ERa-bound enhancers . Furthermore, it was reported recently that a group of enhancers, namely active enhancers, were essential for the transcriptional activation of estrogeninduced coding target genes Enhancer -- ChIP-qPCR,qRT-PCR hSiah2 -- -- -- PSR,PTDSR,PTDSR1,ER,ESR,ESRA,ESTRR,Era,NR3A1 siRNA,RT-qPCR -- -- SIAH2,SIAH2,SIAH2 JMJD6,ESR1,JMJD6,ESR1,JMJD6,ESR1 To validate JMJD6 effects on eRNA production, total RNA extracted from MCF7 cells transfected with control siRNA or two independent siRNAs pecifically against JMJD6 in the presence or absence of strogen treatment were subjected to qRT-PCR analysis using primers specifically targeting several ERa and JMJD6 co-bound active enhancers nearby estrogen-induced coding genes, such as FOXC1, SIAH2, GREB1, NRIP1, and SMAD7.;To validate JMJD6 effects on eRNA production, total RNA extracted from MCF7 cells transfected with control siRNA or two independent siRNAs pecifically against JMJD6 in the presence or absence of strogen treatment were subjected to qRT-PCR analysis using primers specifically targeting several ERa and JMJD6 co-bound active enhancers nearby estrogen-induced coding genes, such as FOXC1, SIAH2, GREB1, NRIP1, and SMAD7.;To validate JMJD6 effects on eRNA production, total RNA extracted from MCF7 cells transfected with control siRNA or two independent siRNAs pecifically against JMJD6 in the presence or absence of strogen treatment were subjected to qRT-PCR analysis using primers specifically targeting several ERa and JMJD6 co-bound active enhancers nearby estrogen-induced coding genes, such as FOXC1, SIAH2, GREB1, NRIP1, and SMAD7. To validate JMJD6 effects on eRNA production, total RNA extracted from MCF7 cells transfected with control siRNA or two independent siRNAs specifically against JMJD6 in the presence or absence of estrogen treatment were subjected to RT-qPCR analysis using primers specifically targeting several ERα and JMJD6 co-bound active enhancers nearby estrogen-induced coding genes.;To validate JMJD6 effects on eRNA production, total RNA extracted from MCF7 cells transfected with control siRNA or two independent siRNAs specifically against JMJD6 in the presence or absence of estrogen treatment were subjected to RT-qPCR analysis using primers specifically targeting several ERα and JMJD6 co-bound active enhancers nearby estrogen-induced coding genes.;To validate JMJD6 effects on eRNA production, total RNA extracted from MCF7 cells transfected with control siRNA or two independent siRNAs specifically against JMJD6 in the presence or absence of estrogen treatment were subjected to RT-qPCR analysis using primers specifically targeting several ERα and JMJD6 co-bound active enhancers nearby estrogen-induced coding genes. 29527594 chr6 127033997 127036097 FGF23 Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in various disease states, including chronic kidney disease (CKD). human Low+High throughput A Novel Distal Enhancer Mediates Inflammation-, PTH-, and Early Onset Murine Kidney Disease-Induced Expression of the Mouse Fgf23 Gene. 否 Chronic Kidney Disease Osteocyte Cell Lines E_02_0758 ChIP-seq,CRISPR/Cas9 We therefore utilized chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) data from an osteocyte cell line to identify potential regulatory regions of the Fgf23 gene. Based on ChIP-seq analysis of enhancer_x0002_associated histone modifications, including H3K4 methylation and H3K9 acetylation, we discovered several potential enhancers for Fgf23, one of which was located 16kb upstream of the gene’s transcriptional start site. Enhancer CRISPR/Cas9 ChIP-seq,RT-PCR Fgf23 16kb Enhancer mediates the induction of Fgf23 by inflammation and PTH and facilitates the increase in FGF23 expression in a murine model of CKD ChIP-seq These results suggest that 16kb Enhancer mediates the induction of Fgf23 by inflammation and PTH and facilitates the increase in FGF23 expression in a murine model of CKD. NF-KB1,NF-kappaB,NF-kappaB1,p105,p50,p50/p105;AA959795,HIF-1-alpha,HIF1-alpha,HIF1alpha,MOP1,bHLHe78 ChIP-seq -- -- Fgf23,Fgf23 Nfkb1,Hif1a,Nfkb1,Hif1a Nevertheless, lack of the _x0003_16kb enhancer blunted FGF23 upregulation in a tissue-specific manner by the acute inflammatory inducers lipopolysaccharide (LPS), interleukin-1-beta (IL-1b), and tumor necrosis factor-alpha (TNFa) in bone, non-osseous tissues,and in circulation. Lack of the _x0003_16kb enhancer also inhibited PTH-induced bone Fgf23 mRNA. Moreover, the absence of this Fgf23 enhancer in an oxalate diet-induced murine CKD model prevented the early onset induction of osseous, renal, and thymic Fgf23 mRNA levels and led to a significant blunting of elevated circulating intact FGF23 levels. These results suggest that _x0003_16kb enhancer mediates the induction of Fgf23 by inflammation and PTH and facilitates the increase in FGF23 expression in a murine model of CKD.;Nevertheless, lack of the _x0003_16kb enhancer blunted FGF23 upregulation in a tissue-specific manner by the acute inflammatory inducers lipopolysaccharide (LPS), interleukin-1-beta (IL-1b), and tumor necrosis factor-alpha (TNFa) in bone, non-osseous tissues,and in circulation. Lack of the _x0003_16kb enhancer also inhibited PTH-induced bone Fgf23 mRNA. Moreover, the absence of this Fgf23 enhancer in an oxalate diet-induced murine CKD model prevented the early onset induction of osseous, renal, and thymic Fgf23 mRNA levels and led to a significant blunting of elevated circulating intact FGF23 levels. These results suggest that _x0003_16kb enhancer mediates the induction of Fgf23 by inflammation and PTH and facilitates the increase in FGF23 expression in a murine model of CKD. Advances in genome‐wide techniques such as chromatin immunoprecipitation followed by DNA sequencing (ChIP‐seq) have revealed that the transcriptional regulation of many genes, including receptor activator of NF‐κB ligand (Tnfsf11), vitamin D receptor (Vdr), or matrix metallopeptidase 13 (Mmp13), are mediated through a complex network of Enhancers each providing distinct factor‐ and cell‐type specificity.;Advances in genome‐wide techniques such as chromatin immunoprecipitation followed by DNA sequencing (ChIP‐seq) have revealed that the transcriptional regulation of many genes, including receptor activator of NF‐κB ligand (Tnfsf11), vitamin D receptor (Vdr), or matrix metallopeptidase 13 (Mmp13), are mediated through a complex network of Enhancers each providing distinct factor‐ and cell‐type specificity. 29514092 chr19 61151074 61161722 IRF8 Of the transcription factors pre- dicted to bind to these enhancers, IRF8, essential for monocyte and DC development, was found to be required for the establishment of these en- hancers, particularly those common to both mono- cyte and DC lineages. CBFb, which heterodimerizes with RUNX family transcription factors to bind target genes, is needed for MDP and CDP devel- opment, and its deficiency causes a loss of monocytes, cDCs, and pDCs (Satpathy et al., 2014). human Low+High throughput Transcription Factor IRF8 Governs Enhancer Landscape Dynamics in Mononuclear Phagocyte Progenitors. 否 -- Mononuclear cell,dendritic cell E_02_0759 ChIP-seq Active enhancers shared by monocytes and DCs (but not neutrophils) and those specific for monocytes were primed and activated with similar kinetics(Figure 2A, left and center). H3K4me1 and H3K27ac ChIP-seq tag densities in these enhancer regions initially increased at the MDP stage.Notably, the expression of genes with primed but not active (often called poised) enhancers was barely induced in monocytes and DCs (Figure S2). We found that the kinetics of DC-specific active enhancers were slower(Figure 2A, right); Super-Enhancer -- ChIP-seq,Transgenic mice,RT-qPCR CD116,Csfgmra,GM-CSFR,GM-CSF-Ra -- -- -- AI893568,ICSBP,IRF-8,Icsbp1,Myls ChIP-seq,Transgenic mice -- -- Csf2ra Irf8 Representative genome browser images of monocyte- or DC-specific en_x0002_hancers, associated with the Bfsp1 and Ehf genes, respec_x0002_tively, are depicted in Figures 2B and 2C.Thus, monocyte_x0002_and/or DC-specific active enhancers are gradually established at progenitor stages prior to the expression of associated genes. Analysis of Enhancer landscapes in Irf8–/– mononuclear phagocyte progenitors and ChIP-seq of IRF8 binding sites in wild-type (WT) cells uncovered a critical role for IRF8.Using an in vitro monocyte differentiation system, we additionally showed that IRF8 binds to promoter-distal enhancers and promotes H3K4me1 enrichment at its binding sites.Consistent with these data, the correlation coefficient of H3K4me1 ChIP-seq tag densities between WT MDPs and Irf8–/– MDPs was lower than that of the microarray data. 29511351 chr4 84277627 84281723 HPSE HPSE enhancer RNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis. human Nervous Low+High throughput HPSE enhancer RNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis 否 Gastric Cancer AGS E_02_0760 3C,ChIP-seq,qPCR Overlapping analysis of FANTOM5 expression atlas and chromatin interaction dataset derived from 4DGenome revealed one potential enhancer region (chr4:84277627–84281723) adjacent to human HPSE promoter(chr4: 84255915–84256935). Chromosome conformation capture (3C) and nucleic acid sequencing revealed the endogenous chromatin looping between HPSE promoter and super enhancer in AGS cells Super-Enhancer -- Luciferase Reporter Assay,qPCR HPA,HPA1,HPR1,HPSE1,HSE1 HPSE eRNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis. ChIP,qPCR ChIP and qPCR assay revealed that knockdown or ectopic expression of hnRNPU prevented the increased or decreased binding of hnRNPU or p300 to super Enhancer region following stable ectopic expression or knockdown of HPSE eRNA AT225,G0S30,KROX-24,NGFI-A,TIS8,ZIF-268,ZNF225 ChIP-seq,qPCR -- -- HPSE,HPSE EGR1,EGR1 Dual-luciferase assay revealed that this super enhancer increased the activity of HPSE promoter in gastric cancer cell lines SGC-7901 and AGS, independent of the orientation or location.;Dual-luciferase assay revealed that this super enhancer increased the activity of HPSE promoter in gastric cancer cell lines SGC-7901 and AGS, independent of the orientation or location. ChIP and qPCR assay revealed that ectopic expression or knockdown of HPSE eRNA increased and decreased the enrichment of EGR1 on HPSE promoter,which was attenuated by knockdown or overexpression of hnRNPU or p300, respectively.;ChIP and qPCR assay revealed that ectopic expression or knockdown of HPSE eRNA increased and decreased the enrichment of EGR1 on HPSE promoter,which was attenuated by knockdown or overexpression of hnRNPU or p300, respectively. 29507293 chr15 66074477 66098025 CTCF Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. human bone marrow Low+High throughput Dissecting super-enhancer hierarchy based on chromatin interactions 是 -- Erythroleukemia Cell Lines E_02_0761 Hi-C,ChIP-seq Finally, if an enhancer element within hierarchical SEs overlaps with a bin associated with a z-score greater than the threshold H-score, the element is referred to a hub enhancer, whereas the remaining enhancers at the same SE are termed non-hub enhancers Super-Enhancer CRISPR/Cas9 -- PPP1R108,myr4,KMT3E,ZMYND1,ZNFN3A1,bA74P14.1 Hub enhancers are the major constituents responsible for SE functional and structural organization. ChIP-seq,CRISPR/Cas9 The signals for H3K27ac and DNase I hypersensitivity are slightly higher at hub than other types of Enhancers. ERYF1,GATA-1,GF-1,GF1,NF-E1,NFE1,XLANP,XLTDA,XLTT,SCL,ALL3,BSAPTCL5,bHLHa17,tal-1,ALL3,BSAP,COE1,EBF,O/E-1,OLF1 ChIP-seq -- -- MYO1D,SMYD3 GATA1,TAL1,PAX5,EBF1 we employed CRISPR-Cas9-mediated genome engineering to delete individual hub or non-hub enhancers with paired sgRNAs flanking the enhancer elements at the MYO1D SE.We observed that 3 of the 5 genes within the SE-containing TAD domain MYO1D,TMEM98 and SPACA3)displayed significant downregulation in mRNA expression, whereas the other two genes (PSMD11 and CDK5R1) remained unaffected , suggesting that the MYO1D SE may regulate only a subset of genes within the same TAD domain. Hub Enhancers contain significantly higher ChIP-seq binding signals for lineage-regulating master regulators than non-hub Enhancers, such as GATA1 and TAL1 in K562 cells, and PAX5 and EBF1 in GM12878 cells. 29440643 chr6 138226720 138233280 TNFAIP3 While the widely used immunohistochemical biomarker CD99 shows high sensitivity for Ewing sarcoma. human lymph Low+High throughput Dissection and function of autoimmunity-associated TNFAIP3 (A20) gene enhancers in humanized mouse models 否 Autoimmune Diseases B cell,mononuclear cell E_02_0762 CRISPR/Cas9,Hi-C,ChIP-seq Recent studies have begun to address mammalian enhancer function using CRISPR-mediated genome editing, including in vivo analysis of mouse genes.To identify enhancers activated by inflammatory stimuli,we analyzed ATAC-seq and ChIP-seq data sets generated in our laboratory (GSE43036, GSE9836926, and GSE104638) for chromatin accessibility, binding of PU.1 and C/EBP (which bind to regulatory elements and help define enhancers in myeloid cells), and induction of acetylation of histone 3 lysine 27 (H3K27-Ac), which indicates enhancer activation, at enhancer peaks after LPS stimulation of primary monocytes. Enhancer -- Hi-C,ChIP-seq A20,AISBL,OTUD7C,TNFA1P2 These findings provide insights into enhancers that regulate human A20 expression to prevent inflammatory pathology and autoimmunity. PCR,CRISPR/Cas9 Collectively, the results show that deletion of the TT>A Enhancer at the TNFAIP3 locus results in an autoimmune/inflammatory phenotype most clearly evident as athritis. -- -- -- -- TNFAIP3 -- To guide selection of BACs for generation of humanized transgenic mice, we analyzed chromatin conformation, accessibility, and enhancer-related histone marks at the TNFAIP3 locus using our laboratory’s (GSE4303620, GSE10038321 and previously unpublished data, GSE104628) and ENCODE and NIH Roadmap ChIP-seq data (available at genome.ucsc.edu and roadmapepigenomics.org) and Hi-C data.Analysis of pre-existing high-resolution Hi-C (chromatin conformation) data in GM12878 B cells identified a 305?kb topologically associating domain (TAD) flanked by CTCF sites roughly centered around the TNFAIP3 gene body. -- 29416716 chr14 99770698 99782638 ATP1A1 Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets. human Musculature Low throughput Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets 否 Ewing Sarcoma A673 cell E_02_0763 Luciferase Reporter Assay,qRT-PCR Expression of these genes appeared to be induced by EWSR1-FLI1-bound super-enhancers, which showed high activity in reporter assays.In fact, EWSR1-FLI1 is known to convert non-functional GGAA-microsatellites into potent enhancers to steer a large proportion of its target genes [24–26]. Strong EWSR1-FLI1-dependent enhancer activity of these GGAA-microsatellites in luciferase reporter assays was consistently observed. Super-Enhancer -- qRT-PCR,ChIP-seq ATL1,ATL1-alpha,ATL1-beta,ATL1-delta,ATL1-gamma,CTIP-2,CTIP2,IDDFSTA,IMD49,RIT1,ZNF856B,hRIT1-alpha -- -- -- -- -- -- -- BCL11B,BCL11B,BCL11B --,--,-- These data in cell lines suggested that ATP1A1, BCL11B, and GLG1 may be direct EWSR1-FLI1 target genes. Testing this hypothesis involved analyzing available ChIP-Seq and DNase-Seq data generated in Ewing sarcoma cell lines, which showed strong EWSR1-FLI1-binding to GGAA-microsatellites close to these genes.;These data in cell lines suggested that ATP1A1, BCL11B, and GLG1 may be direct EWSR1-FLI1 target genes. Testing this hypothesis involved analyzing available ChIP-Seq and DNase-Seq data generated in Ewing sarcoma cell lines, which showed strong EWSR1-FLI1-binding to GGAA-microsatellites close to these genes.;These data in cell lines suggested that ATP1A1, BCL11B, and GLG1 may be direct EWSR1-FLI1 target genes. Testing this hypothesis involved analyzing available ChIP-Seq and DNase-Seq data generated in Ewing sarcoma cell lines, which showed strong EWSR1-FLI1-binding to GGAA-microsatellites close to these genes. --;--;-- 29408204 chr3 69863244 70187654 CDK7 High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma. human tumour Low+High throughput High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma 否 Melanoma melanoma cells E_02_0764 ChIP-seq,Western blot,siRNA,qPCR H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) profiling, which marks active enhancers, indicated the presence of SEs at the MITF gene locus in MITF-hi cells and substantially less enhancer signal at the same location in an MITF-lo cell line (LOXIMVI) and a normal human dermal fibroblast line. Super-Enhancer -- qPCR,ChIP-seq CMM8,COMMAD,MI,WS2,WS2A,bHLHe32 -- -- -- CAK,CAK1,CDKN7,HCAK,MO15,STK1,p39MO15 siRNA -- -- MITF CDK7 To identify a set of MITF high- and low-expressing cells, we performed quantitative real-time reverse transcriptase-PCR analysis on 18 melanoma lines and found 8 lines with high MITF (MITF-hi) (>2-fold mean normalized MITF levels) and 5 lines with low MITF (MITF-lo) (200kb of linear genome. We identified genome-wide 110 long-range loop contacts affected in mutant neurons (DESeq2 P<0.05). Unexpectedly, the large majority, 84/110 or 76%, represented clustered, locus-specific ‘loop aggregates’ showing massive weakening, or complete loss, after neuronal Setdb1 ablation (Figure 1d, Supplementary Figure 2c). hese deficits were specific, because ChiP-seq profiling for open chromatin-associated acetyl-H3-lysine 27 (H3K27ac) showed that 96.4% of 1,112 differentially tagged sequences were hyperacetylated in Setdb1-deficient neurons (Figure 2a, Supplementary Tables 1,2). Enhancer -- ChIP-seq AU022152,ESET,KMT1E,mKIAA0067 -- -- -- AW108038 ChIP-seq -- -- Setdb1 Ctcf Therefore, we predicted that higher order chromatin organization at these positions will be highly conserved in human brain cells, and specifically in neurons, with long-range loopings radiating from ~200kb R1 towards cPCDH promoter and Enhancers primarily anchored in chromatin at and around the Setdb1 peak. To explore, we surveyed with 40kb resolution the cPCDH -bound chromosomal contacts in our in situ Hi-C datasets generated from human neurons and their isogenic neural precursors cells (NPC) and NPC-differentiated astrocytes. ChIP-seq data from stem cells and CD19+ B lymphocytes significant CTCF motif enrichment.CTCF motif (red) enrichment in sequences H3K9me3 hypomethylated in KO. (e) (Left) FACS plots showing separation of crosslinked NeuN+ from NeuN? nuclei (adult cortex) for cell-type specific CTCF ChIP-seq. 28667437 chr9 88325101 88326201 Elf2 We describe the existence of an enhancer sequence upstream of the mouse Nt5e minimal promoter and establish that the mouse Nt5e minimal promoter transcriptional activity is negatively regulated by an Elf2-like Ets-related transcription factor in activated mouse liver myofibroblasts. mouse Low throughput An Elf2-like transcription factor acts as repressor of the mouse ecto-5'-nucleotidase gene expression in hepatic myofibroblasts. 否 Hepatic Fibrosis Myofibroblast E_02_0795 Luciferase Reporter Assay The measured luciferase activity noticeably decreased between F1- and F2-Luc constructs, suggesting that F1-Luc construct contains a potential enhancer sequence, which spans approximately 1000 bp (?2069 to ?996 bp) and is absent in the shorter F2-Luc construct. Enhancer -- Luciferase Reporter Assay,PCR 2210401F01Rik,5'-NT,AI447961,CD73,NT,Nt5,eNT -- -- -- 2610036A20Rik,A230104O07Rik,AW111824,BB183398,EU32,NERF,NERF-1A,NERF-1B,NERF-2 Luciferase Reporter Assay -- -- Nt5e Elf2 Luciferase activity as_x0002_says showed that the ENH1074-F5-Luc construct containing the full putative Enhancer (-2069 to -996 bp) sequence has the ability to enhance the luciferase activity of the identified putative mouse Nt5e promoter. We found that mutation of Elf2 responsive element alone was sufficient to significantly increase the F5-Luc construct luciferase activity (F5-Luc, 11.79 ± 1.41 vs. mut Elf2-F5-Luc,20.48 ± 2.96, **p < 0.01).These data indicate that repression of mouse Nt5e promoter activity is likely mediated by transcription factor(s) acting at the identified Elf2 site in NIH3T3 fibroblasts. 28637769 Chr11 45846943 45846959 CRY2 Although CRY2 is a core component of the mammalian circadian clock (van der Horst et al., 1999), the mechanism of the circadian transcription of this gene has yet to be analyzed in detail. In the present study, we found that cell-autonomous circadian transcription of the Cry2 gene requires a functionally interdependent tandem E-box motif. human Epithelial Low throughput Potential contribution of tandem circadian enhancers to nonlinear oscillations in clock gene expression 否 -- U-2 OS cell E_02_0796 Luciferase Reporter Assay To identify components necessary for cell-autonomous circadian transcription of the hCry2 gene, a 3-kbp 5'-flanking region upstream from the hCry2 transcription start site was isolated and subcloned into the upstream of the luciferase gene, and the hCry2-driven luciferase activity was monitored in real time using a cell-based system (Figure 1A).To exclude systemic factors such as blood-borne factors and body temperature, it was necessary to examine cell-autonomous transcriptional regulatory mechanisms under an in vitro culture condition. The data clearly showed a robust circadian oscillation of the bioluminescence in U2OS human steosarcoma cells (Figure 1B), indicating that the cloned genomic region contained elements essential for circadian transcription.The 60-bp region is functionally divided into two; a 43-bp region (from -158 to -116) contains elements which enhance oscillation amplitude, while the 17-bp region (from -175 to -159) is indispensable for the generation of transcriptional oscillation. After narrowing down the transcriptional regulatory region required for the cell-autonomous circadian transcription of hCry2,and further narrowing down the genomic region essential for cell-autonomous circadian transcription,the results strongly suggested that the essential regulatory elements are contained in the region from -175 to -116 (60-bp length) (Figure 1D). To identify consensus sequences for transcription factor binding within the latter region, we performed an in silico search by sequence alignment, and found interspecies-conserved E-boxes within the 17-bp region (E1 and E2, Figure 1C). To investigate whether each of the E-boxes is functional for circadian transcription of the hCry2 gene, we produced constructs carrying hCry2 lacking either one of the E-boxes (Figure 2A). To confirm whether the BMAL1 and CLOCK complex actually activates hCry2 transcription via each E-box, we performed dual luciferase assays with these constructs (Figures 2B). The data showed that overexpression of BMAL1 and CLOCK activated hCry2 transcription via the region spanning from -249 to +41, and that deletion of one of the E-boxes produced severe attenuation of transcription, while deletion of both produced an almost complete loss of activation. Enhancer -- Luciferase Reporter Assay HCRY2,PHLL2 the interdependent behavior of enhancer elements including not only E-boxboxes but also ROR response elements (ROREs) might contribute to limit cycle oscillations by increasing transcriptional nonlinearity. EMSA Immunoprecipitation was performed with antibody-conjugated beads, and the immunoprecipitates were eluted with an excess amount of tag-peptide.A mutation of E1 resulted in a severe attenuation of the affinity of the BMAL1 and CLOCK complex to the probe, and the position of the shifted band was slightly changed, probably because of the reduction of the mole ratio between the binding proteins and probe. A mutation of E2 led to almost complete loss of the physical interaction between them. Taken together, the present EMSA data indicate that each of the hCry2 tandem E-boxes physically interacts directly with the BMAL1 and CLOCK complex in an interdependent and not independent manner. BMAL1,BMAL1c,JAP3,MOP3,PASD3,TIC,bHLHe5,KAT13D, bHLHe8 EMSA,Pull-down assay -- -- CRY2 ARNTL,CLOCK To identify components necessary for cell-autonomous circadian transcription of the hCry2 gene, a 3-kbp 5'-flanking region upstream from the hCry2 transcription start site was isolated and subcloned into the upstream of the luciferase gene, and the hCry2-driven luciferase activity was monitored in real time using a cell-based system (Figure 1A).To exclude systemic factors such as blood-borne factors and body temperature, it was necessary to examine cell-autonomous transcriptional regulatory mechanisms under an in vitro culture condition. The data clearly showed a robust circadian oscillation of the bioluminescence in U2OS human steosarcoma cells (Figure 1B), indicating that the cloned genomic region contained elements essential for circadian transcription.The 60-bp region is functionally divided into two; a 43-bp region (from -158 to -116) contains elements which enhance oscillation amplitude, while the 17-bp region (from -175 to -159) is indispensable for the generation of transcriptional oscillation. After narrowing down the transcriptional regulatory region required for the cell-autonomous circadian transcription of hCry2,and further narrowing down the genomic region essential for cell-autonomous circadian transcription,the results strongly suggested that the essential regulatory elements are contained in the region from -175 to -116 (60-bp length) (Figure 1D). To identify consensus sequences for transcription factor binding within the latter region, we performed an in silico search by sequence alignment, and found interspecies-conserved E-boxes within the 17-bp region (E1 and E2, Figure 1C). To investigate whether each of the E-boxes is functional for circadian transcription of the hCry2 gene, we produced constructs carrying hCry2 lacking either one of the E-boxes (Figure 2A). To confirm whether the BMAL1 and CLOCK complex actually activates hCry2 transcription via each E-box, we performed dual luciferase assays with these constructs (Figures 2B). The data showed that overexpression of BMAL1 and CLOCK activated hCry2 transcription via the region spanning from -249 to +41, and that deletion of one of the E-boxes produced severe attenuation of transcription, while deletion of both produced an almost complete loss of activation. We therefore performed electrophoretic mobility shift assays (EMSAs) to investigate the physical interaction of purified BMAL1 and CLOCK proteins to double-stranded DNA fragments (Figure 3A).We confirmed that the electrophoretic mobility of the probe was shifted by the physical interaction with BMAL1–CLOCK. A mutation of E1 resulted in a severe attenuation of the affinity of the BMAL1 and CLOCK complex to the probe, and the position of the shifted band was slightly changed, probably because of the reduction of the mole ratio between the binding proteins and probe. A mutation of E2 led to almost complete loss of the physical interaction between them. Taken together, the present EMSA data indicate that each of the hCry2 tandem E-boxes physically interacts directly with the BMAL1 and CLOCK complex in an interdependent and not independent manner. Next, we performed hCry2-oligodeoxynucleotide (ODN) pull-down assays and confirmed that endogenous BMAL1 and CLOCK expressed in the liver bound to a fragment containing the hCry2 tandem E-boxes (Figure 3B). 28614915 chr17 62627957 62633457 Ascl1 Further comparative genomic analysis indicated that two evolutionary conserved regions, ECR1 and ECR2, were present within this 5.5 kb region. Finally, both electrophoretic mobility shift assay and luciferase-based transactivation assay revealed that the transcription factor Ascl1 bound the bHLH consensus binding site in the mesencephalon-specific ephrin-A5 enhancer in vitro. mouse Low throughput Identification of an Enhancer Critical for the ephirn-A5 Gene Expression in the Posterior Region of the Mesencephalon. 否 -- Mesencephalon E_02_0797 Luciferase Reporter Assay Luciferase activity assay showing that Ascl1- E47 fusion protein induces transcriptional activation through the ephrin-A5 E-box DNA.Taken together, our findings suggest that the mesencephalon-specific enhancer of ephrin-A5 resided in a genomic region that is +11.6 kb to +57.7 kb from the TSS and is within the first intron (Fig. 1A). Enhancer -- Luciferase Reporter Assay,PCR AL-1,AV158822,EFL-5,Ephrin-A5,Epl7,LERK-7,RAGS -- -- -- AI225900,ASH1,Mash1,bHLHa46 EMSA,Luciferase Reporter Assay -- -- Efna5 Ascl1 To further restrict the possible locations of the mesencephalon-specific enhancer within the first intron, the 375B7 BAC was modified using a different targeting vector. Importantly, transgenic embryos carrying this recombinant BAC did not show significant LacZ expression in the mesencephalon (Fig. 2C, first panel from the left). This suggested that the deleted 30.4 kb region included the mesencephalon-specific enhancer of ephrin-A5.This suggests that the potential enhancer for ephrin-A5 expression in the mesencephalon was in a 5.5 kb genomic region from +25 kb to +30.5 kb of the TSS. Finally, both electrophoretic mobility shift assay and luciferase-based transactivation assay revealed that the transcription factor Ascl1 bound the bHLH consensus binding site in the mesencephalon-specific ephrin-A5 enhancer in vitro. 28578223 chr18 61533339 61545796 SERPINB2 The SERPINB2 gene is strongly upregulated in inflammatory states. In monocytes, it can constitute up to 1% of total cellular protein. It functions in protection from proteotoxic stress and plays a role in angioedema. human blood Low+High throughput SERPINB2 is regulated by dynamic interactions with pause-release proteins and enhancer RNAs 否 -- MonoMac6,K-562 cell E_02_0798 ChIP-seq,Luciferase Reporter Assay,qRT-PCR A cluster of RNAs, not previously annotated, was found approximately 21 kb upstream of the SERPINB2 gene in SLE monocytes (Shi et al.,2014). The RNAs (772, 774, 775) formed a cluster near an enhancer, de?ned by H3K27ac in UCSC Genome Browser. 774 is centered on the H3K27ac peak, 775 is at the proximal edge of the H3K27ac peak and 772 is at the distal shores of the H3K27ac peak. We will refer to this region as Enhancer 1. We tested the DNA corresponding to the 775 ncRNA in an enhancer assay by sub-cloning it downstream of a minimal thymidine kinase (TK) promoter. The DNA corresponding to the 775 ncRNA location was capable of augmenting luciferase production in this transient transfection assay in two di?erent cell types (K562 and HEK293), thereby assigning it as a probable enhancer (Fig. 2A and B). For this reason, we will refer to the ncRNAs subsequently as eRNAs. Enhancer RNAs are predicted to have chromatin localization. To validate the remaining eRNAs, we used qRT-PCR from three di?erent cell types to demonstrate tissue speci?city and analyzed eRNA sub-cellular localization by fractionating cells. The eRNAs were found predominantly in monocytes and in the chromatin and nucleoplasm fractions predominantly (Fig. 2C and D). This demonstration of enhancer activity of the DNA and chromatin localization support the assignment of the ncRNAs as eRNAs. Enhancer -- ChIP-seq,Luciferase Reporter Assay,qRT-PCR HsT1201,PAI,PAI-2,PAI2,PLANH2 Knock-down of the enhancer RNAs compromised stimulus induction of promoter and enhancer chromatin changes. Conversely,over-expression was associated with enhanced recruitment of c-JUN and increased expression of SERPINB2 mRNA expression. qRT-PCR We knocked down 774 and 775 as SERPINB2-speci?c eRNAs. Knock-down was validated by qRT-PCR of the target eRNAs. Knock-down of 774 and 775 led to inhibition of SERPINB2 mRNAs but not SERPINB10, which is not co-regulated with SERPINB2 (Fig. 3B). We then over-expressed 774 and 775 to determine whether they could regulate SERPIN gene expression when provided in trans. Each over-expression construct was validated as expressing the correct RNA species (Fig. 3C). Over-expression of both 774 and 775 led to higher SERPINB2 RNA but not the distinctly regulated SERPINB10.Ano?-target, control RNA, 477, had no e?ect. Enhancer RNAs have been hypothesized to regulate gene expression via diverse potential mechanisms. We tested whether they regulated histone modi?cations. To de?ne e?ects related to eRNAs, we used anti-sense oligonucleotides to knock-down 774 and 775.We examined chromatin marks of gene activation in MonoMac6 cells at baseline and after treatment with LPS (Fig. 4C–F). We compared the e?ects of 774 and 775 knock-down with GFP knock-down. Non-transfected cells were included as assay controls for each experiment but are not shown to streamline the ?gures.The GAPDH promoter was una?ected by LPS stimulation and serves as a control. The anti-sense oligonucleotides to 774 and 775 were associated with diminished acquisition of the chromatin marks seen with LPS stimulation at Enhancer 1. The e?ect was limited to LPS-stimulated cells and was not observed in resting cells. Knock-down of 774 and 775 primarily a?ected H3K4me3 and H3K27ac at the promoter. These data demonstrate that eRNAs regulate histone modi?cations not just at the enhancer but also at their target gene promoter. HH9,NELF,C-2k,CDC2L4,CTK1,PITALRE,TAK ChIP -- -- SERPINB2 NSMF,CDK9 A cluster of RNAs, not previously annotated, was found approximately 21 kb upstream of the SERPINB2 gene in SLE monocytes (Shi et al.,2014). The RNAs (772, 774, 775) formed a cluster near an enhancer, de?ned by H3K27ac in UCSC Genome Browser. 774 is centered on the H3K27ac peak, 775 is at the proximal edge of the H3K27ac peak and 772 is at the distal shores of the H3K27ac peak. We will refer to this region as Enhancer 1. We tested the DNA corresponding to the 775 ncRNA in an enhancer assay by sub-cloning it downstream of a minimal thymidine kinase (TK) promoter. The DNA corresponding to the 775 ncRNA location was capable of augmenting luciferase production in this transient transfection assay in two di?erent cell types (K562 and HEK293), thereby assigning it as a probable enhancer (Fig. 2A and B). For this reason, we will refer to the ncRNAs subsequently as eRNAs. Enhancer RNAs are predicted to have chromatin localization. To validate the remaining eRNAs, we used qRT-PCR from three di?erent cell types to demonstrate tissue speci?city and analyzed eRNA sub-cellular localization by fractionating cells. The eRNAs were found predominantly in monocytes and in the chromatin and nucleoplasm fractions predominantly (Fig. 2C and D). This demonstration of enhancer activity of the DNA and chromatin localization support the assignment of the ncRNAs as eRNAs. To examine whether NELF and its major kinase are localized to the promoter and Enhancer of SERPINB2, we performed ChIP studies for NELF and CDK9. 28536097 chr1 221049243 221051243 DLL4 By assessing the signals responsible for induction of the Notch ligand, Delta-Like 4 (DLL4) in endothelial cells we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. human connective Low+High throughput Dynamic regulation of VEGF-inducible genes by an ERK-ERG-p300 transcriptional network 否 -- HUVEC E_02_0799 ChIP-seq,Luciferase Reporter Assay,ChIP We also performed H3K27ac ChIP-seq and found that 94% of conserved ERG peaks overlapped H3K27ac-enriched regions, supporting their association with active enhancers. We also identified an ERG-bound enhancer, conserved in cows and humans, ~3.0 kb upstream of the gene H2.0-Like Homeobox (HLX) (Fig. 8B; Fig. S8). We cloned this conserved H3K27ac- and ERG-enriched -3 kb 5’ putative regulatory region (HLX-3a, 1565 bp fragment) upstream of a minimal promoter (SV40) driving a luciferase reporter, and found that it was VEGF-responsive, and that the basal and VEGF-induced activity of this enhancer required ETS DNA binding sequences (Fig. 9D). Enhancer -- ChIP-seq,Luciferase Reporter Assay HB241, HLX A highly-conserved ERG-bound regulatory element was required in the VEGF responsiveness of the angiogenic gene, HLX. CRISPR/Cas9,PCR To further test the functional importance of this enhancer, we utilized CRISPR genome editing to delete a portion (1201 bp; see Fig. 8B for schematic) of the H3K27Ac-enriched, ERG-bound region upstream of HLX in TeloHAECs, an immortalized aortic EC line. Several clonal lines (ΔHLX15, ΔHLX17 and ΔHLX21) heterozygous for deletion of this region were generated and confirmed by PCR and DNA sequencing (data not shown). Comparison was made to a clonal line generated following transfection of scrambled control gRNAs (Scr3). While the basal expression of HLX appeared to be unaffected in the deletion lines, the VEGF-dependent induction of HLX was attenuated (Fig. 9G). In contrast, DLL4 induction was unaffected. Furthermore, knock-down of ERG appeared to attenuate the induction of HLX to a greater extent in the control line compared to the deletion lines, implying that ERG acts through the deleted enhancer region. Collectively, these findings demonstrate the requirement of a highly-conserved ERG-bound regulatory element in the VEGF responsiveness of the angiogenic gene, HLX. MVCD1,VEGF,VPF,erg-3,p55 Luciferase Reporter Assay -- -- HLX,HLX VEGF,ERG,VEGF,ERG We also performed H3K27ac ChIP--seq and found that 94% of conserved ERG peaks overlapped H3K27ac--enriched regions, supporting their association with active enhancers. We also identified an ERG--bound enhancer, conserved in cows and humans, ~3.0 kb upstream of the gene H2.0--Like Homeobox (HLX) (Fig. 8B; Fig. S8). We cloned this conserved H3K27ac-- and ERG--enriched --3 kb 5’ putative regulatory region (HLX--3a, 1565 bp fragment) upstream of a minimal promoter (SV40) driving a luciferase reporter, and found that it was VEGF--responsive, and that the basal and VEGF--induced activity of this enhancer required ETS DNA binding sequences (Fig. 9D).;We also performed H3K27ac ChIP--seq and found that 94% of conserved ERG peaks overlapped H3K27ac--enriched regions, supporting their association with active enhancers. We also identified an ERG--bound enhancer, conserved in cows and humans, ~3.0 kb upstream of the gene H2.0--Like Homeobox (HLX) (Fig. 8B; Fig. S8). We cloned this conserved H3K27ac-- and ERG--enriched --3 kb 5’ putative regulatory region (HLX--3a, 1565 bp fragment) upstream of a minimal promoter (SV40) driving a luciferase reporter, and found that it was VEGF--responsive, and that the basal and VEGF--induced activity of this enhancer required ETS DNA binding sequences (Fig. 9D). We cloned this conserved H3K27ac- and ERG-enriched -3 kb 5’ putative regulatory region (HLX-3a, 1565 bp fragment) upstream of a minimal promoter (SV40) driving a luciferase reporter, and found that it was VEGF-responsive, and that the basal and VEGF-induced activity of this enhancer required ETS DNA binding sequences (Fig. 9D). ;We cloned this conserved H3K27ac- and ERG-enriched -3 kb 5’ putative regulatory region (HLX-3a, 1565 bp fragment) upstream of a minimal promoter (SV40) driving a luciferase reporter, and found that it was VEGF-responsive, and that the basal and VEGF-induced activity of this enhancer required ETS DNA binding sequences (Fig. 9D). 28511927 chr11 355447 358949 STAT1 The enhancer drove the coordinate expression of IFITM1, 2 and 3 through constitutive long-range interactions and IFNβ-induced STAT1 binding. human kidney Low throughput Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer through long-range chromatin interactions 否 -- A549,HEK-293 cell E_02_0800 Luciferase Reporter Assay,CRISPR/Cas9,ChIP,EMSA,3C Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35 kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. Finally, we showed that in vivo truncation of the enhancer impaired IFN-induced resistance to influenza A virus (IAV) infection. Enhancer CRISPR/Cas9,3C Luciferase Reporter Assay,EMSA 927,CD225,DSPA2a,IFI17,LEU13,1-8D,DSPA2c,1-8U,DSPA2b,IP15 In vivo truncation of the enhancer impaired IFN-induced resistance to influenza A virus (IAV) infection. RT-PCR,Western blot As IFITM1, 2 and 3 are very important for host to resist infection of IAV [4], [8], we infected wild-type and E2-3-truncated HEK293 cells with IAV Puerto Rico/8/1934 (PR8) at a MOI of 0.1 for 24 h. Although IFITM1, 2 and 3 were induced by PR8 virus in both wild-type and E2-3-truncated HEK293 cells, the inductions were greatly impaired upon truncation of E2-3 (Fig. 5A and B), further confirming the regulation of IFITM1, 2 and 3 expression by the enhancer E2-3. Surprisingly, we did not observe a significant effect on the replication of IAV when enhancer E2-3 was truncated, as revealed by the mRNA and protein levels of virus NP and progeny virus titers determined by TCID50 assay (Fig. S9). Nonetheless, when we treated wild-type and E2-3-truncated HEK293 cells with IFNβ respectively for 24 h before infection of PR8, NP mRNA and protein levels were found to be much higher in mutant HEK293 cells (Fig. 5C and D). Moreover, consistent with virus NP expression, the viral titers were also increased in E2-3-truncated cells (Fig. 5E), indicating that enhancer E2-3 was responsible for IFNβ-induced resistance to IAV infection. CANDF7,IMD31A,IMD31B,IMD31C,ISGF-3,STAT91 ChIP,EMSA,3C -- -- IFITM1,IFITM2,IFITM3,IFITM1,IFITM2,IFITM3,IFITM1,IFITM2,IFITM3 STAT1,STAT1,STAT1 Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35 kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer.;Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35 kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer.;Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35 kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. ;Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. ;Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. 28446439 chr11 17666830 17677080 MYOG P3F uses SEs to setup auto-regulatory loops in collaboration with master transcription factors MYOG, MYOD and MYCN. human lung Low+High throughput PAX3-FOXO1 establishes myogenic super enhancers and confers BET bromodomain vulnerability 否 Alveolar Rhabdomyosarcoma Human Fibroblast Cell Lines E_02_0801 ChIP-seq,4C,Luciferase Reporter Assay We found PAX3-FOXO1 most frequently occupied the strong Enhancer chromatin state , exemplified by known PAX3-FOXO1 target FGFR4 and oncogenes MYC, ALK and MET Super-Enhancer 4C ChIP-seq,Luciferase Reporter Assay MYF3,MYOD,PUM,bHLHc1 -- -- -- CDHS,HUP2,WS1,WS3,FKH1,FKHR,FOXO1A ChIP-qPCR,ChIP-seq -- -- MYOD1,MYOD1 PAX3,FOXO1,PAX3,FOXO1 We found PAX3-FOXO1 most frequently occupied the strong Enhancer chromatin state , exemplified by known PAX3-FOXO1 target FGFR4 and oncogenes MYC, ALK and MET;We found PAX3-FOXO1 most frequently occupied the strong Enhancer chromatin state , exemplified by known PAX3-FOXO1 target FGFR4 and oncogenes MYC, ALK and MET To gain insight into the epigenetic consequences of PAX3-FOXO1, we mapped the landscape of active and repressive histone marks by sequencing DNA enriched by chromatin immunoprecipitation (ChIP-seq) from a patient derived fusion positive FP-RMS cell line RH4. ;To gain insight into the epigenetic consequences of PAX3-FOXO1, we mapped the landscape of active and repressive histone marks by sequencing DNA enriched by chromatin immunoprecipitation (ChIP-seq) from a patient derived fusion positive FP-RMS cell line RH4. 28378740 chr3 107702615 107714185 CD47 CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPa, on macrophages and other immune cells. human breast Low+High throughput A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer 否 Breast Cancer MCF-7 cell E_02_0802 ChIP-seq,Luciferase Reporter Assay By rank-ordering of enhancer regions based on H3K27ac enrichment, we discovered that T-cell acute lymphoblastic leukemia (T-ALL (RPMI18402, Jurkat and MOLT3)) diffuse large B-cell lymphoma (DLBCL (LY4)) and breast cancer (MCF7 and HCC1954) cell lines have SEs within B200 kb of CD47 (Fig. 1a). To validate their function experimentally, we cloned each candidate CD47 enhancer (E1–9) into an EGFP reporter lentiviral construct containing the minimal (basal) promoter for the thymidine kinase (TK) gene7. We found that two of the CD47 enhancers (E5 and E3.2) had MCF7- and Jurkat-speci?c regulatory activity (Fig. 2a–c).First, E5, in the downstream CD47 SE seen in breast cancers (Fig. 1a,b), showed increased reporter activity speci?cally in the MCF7 breast cancer cell line (Fig. 2a). Further analysis of publicly available Paired-End Tag (ChIA-PET) data22,23 con?rmed that E5 and the downstream CD47 SE in MCF7 are connected by a DNA loop containing RNA Polymerase II.Second, we found that E3.2, located within the upstream CD47 SE (Fig. 1a), had increased reporter expression speci?cally in the Jurkat cell line (Fig. 2b). We also found that a third functional enhancer, E7, located within the upstream CD47 SE (Fig. 1a), drove reporter expression in all of the cancer cell lines tested (Fig. 2d). Enhancer -- ChIP-seq,Luciferase Reporter Assay IAP,MER6,OA3 -- -- -- CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NFKB-p105,NFKB-p50,NFkappaB,p105,p50 shRNA -- -- CD47 NFKB1 To validate their function experimentally, we cloned each candidate CD47 enhancer (E1–9) into an EGFP reporter lentiviral construct containing the minimal (basal) promoter for the thymidine kinase (TK) gene7. We found that two of the CD47 enhancers (E5 and E3.2) had MCF7- and Jurkat-speci?c regulatory activity (Fig. 2a–c).First, E5, in the downstream CD47 SE seen in breast cancers (Fig. 1a,b), showed increased reporter activity speci?cally in the MCF7 breast cancer cell line (Fig. 2a). Further analysis of publicly available Paired-End Tag (ChIA-PET) data22,23 con?rmed that E5 and the downstream CD47 SE in MCF7 are connected by a DNA loop containing RNA Polymerase II.Second, we found that E3.2, located within the upstream CD47 SE (Fig. 1a), had increased reporter expression speci?cally in the Jurkat cell line (Fig. 2b). We also found that a third functional enhancer, E7, located within the upstream CD47 SE (Fig. 1a), drove reporter expression in all of the cancer cell lines tested (Fig. 2d). We?observed?that?72?h?after?shRNA?transduction,?expression?of?CD47?transcript?and?protein?(measured?by?flow?cytometry)?was?significantly?reduced?by?NFKB1?(Fig.?3b,c)?and?PPARα?(Fig.?3b,?Supplementary?Fig.?3d,e)?shRNAs,?when?compared?to?control?shRNA.?On?the?other?hand,?shRNAs?against?STATs?3,?5?and?6?did?not?reduce?CD47?expression?significantly?(Fig.?3b).?This?information?demonstrates?that?NFKB?and?PPAR?are?involved?in?the?regulation?of?CD47?in?MCF7?cells?and?since?knocking?down?NFKB1?had?the?strongest?effect?on?CD47?gene?expression,?we?focus?this?study?on?the?regulatory?role?of?this?transcription?factor. 28335007 chr5 9034150 9036900 CLOCK It is now known that the central molecular clock is formed by two main feedback loops consisting of core clock genes (1 4). In the first loop, BMAL1 and CLOCK form heterodimers to initiate the expression of Period (Per1/2/3) and Cryptochrome (Cry1/2) genes that in return repress BMAL1/CLOCK activities. human Low+High throughput A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation. 否 -- hepatocyte E_02_0803 ChIP-seq On the other hand, the enhancer regions associated with lncRNAs tended to have much higher intensities of H3K27ac marks than the enhancers not associated with lncRNAs (KS test, P-value < 2.2 × 10?16) (Figure ?(Figure2E).2E). The enhancers associated with circadian lncRNAs have even higher levels of H3K27ac marks than those associated with lncRNAs (KS test, P-value = 0.0017). Taken together, there is a strong association between circadian lncRNAs and super-enhancers. Super-Enhancer 4C qPCR,RNA-seq,ChIP-seq lnc-Crot Enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. qPCR,CRISPR/Cas9 Our result points to a model that the lnc-Crot locus and nearby genes first form a scaffold upon which histone modifications and TF bindings then take place to confer tissue- and time-dependent expression (Figure ?(Figure5G).5G). The circadian lncRNAs that we examined may be a result of circadian transcription at the enhancer regions while the lncRNAs themselves do not influence the circadian gene regulation. Arnt3,BMAL1b,Bmal1,MOP3,bHLHe5,bmal1b',RVR,Rev-erb ChIP-seq,RNA-seq,Knockout mice -- -- Gm40264,Gm40264 Arntl,Nr1d2,Arntl,Nr1d2 The enhancers defined from mouse liver GRO-seq and 5? CAGE technology were consistent with H3K27ac marks of enhancer at this lnc-Crot region (Supplementary Figure S3C). Using RACE assay, we obtained the full-length sequence of lnc-Crot (Figure ?(Figure4B).4B). Both BMAL1 and REV-ERBα binding sites were found on the promoter and gene body of lnc-Crot (Figure ?(Figure4B)4B) but not on the promoters of nearby circadian genes including Crot, Tmem243 and Dmtf1 (Supplementary Figure S3D).By qPCR, we showed that Crot and lnc-Crot were co-expressed (r = 0.8) across adult mouse tissues with elevated expression in liver and kidney (Supplementary Figure S3F).4C signals from three biological replicates at each circadian time were highly reproducible judging from their cross-sample correlations between 0.89 and 0.95. About 44% of 4C signals fell within chromosome 5 where lnc-Crot is situated and the signal profile around lnc-Crot region was displayed in Supplementary Figure S5A. ;The enhancers defined from mouse liver GRO-seq and 5? CAGE technology were consistent with H3K27ac marks of enhancer at this lnc-Crot region (Supplementary Figure S3C). Using RACE assay, we obtained the full-length sequence of lnc-Crot (Figure ?(Figure4B).4B). Both BMAL1 and REV-ERBα binding sites were found on the promoter and gene body of lnc-Crot (Figure ?(Figure4B)4B) but not on the promoters of nearby circadian genes including Crot, Tmem243 and Dmtf1 (Supplementary Figure S3D).By qPCR, we showed that Crot and lnc-Crot were co-expressed (r = 0.8) across adult mouse tissues with elevated expression in liver and kidney (Supplementary Figure S3F).4C signals from three biological replicates at each circadian time were highly reproducible judging from their cross-sample correlations between 0.89 and 0.95. About 44% of 4C signals fell within chromosome 5 where lnc-Crot is situated and the signal profile around lnc-Crot region was displayed in Supplementary Figure S5A. We defined BMAL1 and REV-ERB binding sites from two sets of BMAL1 ChIP-seq studies and two sets of REV-ERB ChIP-seq data in mouse liver respectively, resulting in 8001 BMAL1and 17545REV-ERB binding sites.Atotal of 259 (43%) circadian lncRNA clusters contain either BMAL1 or REV-ERB binding sites.For each lncRNA cluster, we quantified its expression in the BMAL1 knockout and WT mouse livers at CT0 and CT12 using our RNA-seq data.This suggested that circadian lncRNAs were regulated by these two master circadian TFs in the similar way as circadian protein coding genes.Circadian expression of lnc-Crot was disrupted when BMAL1 or REV-ERBα was knocked out, resulting in its downregulation at CT0 in BMAL1 knockout mice and upregulation at CT12 in REV-ERBα knockout mice (Figure ?(Figure4B,4B, Supplementary Figure S3E). This demonstrated that lnc-Crot was directly regulated by BMAL1 and REV-ERBα.;We defined BMAL1 and REV-ERB binding sites from two sets of BMAL1 ChIP-seq studies and two sets of REV-ERB ChIP-seq data in mouse liver respectively, resulting in 8001 BMAL1and 17545REV-ERB binding sites.Atotal of 259 (43%) circadian lncRNA clusters contain either BMAL1 or REV-ERB binding sites.For each lncRNA cluster, we quantified its expression in the BMAL1 knockout and WT mouse livers at CT0 and CT12 using our RNA-seq data.This suggested that circadian lncRNAs were regulated by these two master circadian TFs in the similar way as circadian protein coding genes.Circadian expression of lnc-Crot was disrupted when BMAL1 or REV-ERBα was knocked out, resulting in its downregulation at CT0 in BMAL1 knockout mice and upregulation at CT12 in REV-ERBα knockout mice (Figure ?(Figure4B,4B, Supplementary Figure S3E). This demonstrated that lnc-Crot was directly regulated by BMAL1 and REV-ERBα. 28262837 chr9 97396388 97401553 AKT1 For example, AKT1 stimulates glycolysis by increasing the expression and membrane translocation of glucose trans_x0002_porters, and by phosphorylating key glycolytic enzymes such as hexokinase and phosphofructokinase-22,3. human liver Low+High throughput Inhibiting histone deacetylases suppresses glucose metabolism and hepatocellular carcinoma growth by restoring FBP1 expression 否 Hepatocellular carcinoma Hepatocellular carcinoma E_02_0804 ChIP-seq,ChIP,RT-PCR We noticed that there is a putative H3K4me1-positive enhancer region in the first intron of the FBP1 gene (Fig.?4E).Importantly, we found that at the same region there is a peak of histone H3 lysine-27 acetylation (H3K27Ac) (Fig.?4E), the level of which often correlates with transcriptional activity of the gene. We first examined whether treatment of the HDAC inhibitor NaBu affects H3K27Ac levels in this region. To this end, we erformed chromatin immunoprecipitation (ChIP) assays using H3K27Ac-specific antibody. As demonstrated in Fig.?4F, the H3K27Ac level was readily detectable in the enhancer region of FBP1 gene in both HepG2 and SK-Hep1 cell lines.However, consistent with the finding that NaBu treatment markedly increased expression of FBP1 mRNA (Fig.?2A), it also significantly increased H3K27Ac level in the FBP1 enhancer (Fig.?4F). Similar to the finding that HDAC1 and HDAC2 knockdown induced FBP1 expression, depletion of these proteins alone or together also largely increased H3K27Ac level at this locus (Fig.?4G). This data indicate that the FBP1 gene locus indeed harbors a regulatory region where H3K27Ac level can be modulated by HDAC proteins. Thus, HDAC inhibitor-induced upregulation of H3K27 acetylation in the enhancer of the FBP1 gene correlates with increased expression of FBP1 induced by HDAC inhibitors. Enhancer -- ChIP-seq,ChIP,RT-PCR FBP HDAC-mediated suppression of FBP1 expression correlated with decreased histone H3K27Ac in the FBP1 enhancer. ChIP,RT-PCR Real-time PCR analysis of DNA mmunoprecipitated by control IgG or H3K27Ac antibody from HepG2 and SK-Hep1 cells transfected with control or HDAC1- and/or HDAC2-specific siRNAs. Cells harvested for ChIP assay at 48 hours after transfectio. -- -- -- -- FBP1,FBP1,FBP1 --,--,-- We noticed that there is a putative H3K4me1-positive enhancer region in the first intron of the FBP1 gene (Fig.?4E).Importantly, we found that at the same region there is a peak of histone H3 lysine-27 acetylation (H3K27Ac) (Fig.?4E), the level of which often correlates with transcriptional activity of the gene. We first examined whether treatment of the HDAC inhibitor NaBu affects H3K27Ac levels in this region. To this end, we erformed chromatin immunoprecipitation (ChIP) assays using H3K27Ac-specific antibody. As demonstrated in Fig.?4F, the H3K27Ac level was readily detectable in the enhancer region of FBP1 gene in both HepG2 and SK-Hep1 cell lines.However, consistent with the finding that NaBu treatment markedly increased expression of FBP1 mRNA (Fig.?2A), it also significantly increased H3K27Ac level in the FBP1 enhancer (Fig.?4F). Similar to the finding that HDAC1 and HDAC2 knockdown induced FBP1 expression, depletion of these proteins alone or together also largely increased H3K27Ac level at this locus (Fig.?4G). This data indicate that the FBP1 gene locus indeed harbors a regulatory region where H3K27Ac level can be modulated by HDAC proteins. Thus, HDAC inhibitor-induced upregulation of H3K27 acetylation in the enhancer of the FBP1 gene correlates with increased expression of FBP1 induced by HDAC inhibitors.;We noticed that there is a putative H3K4me1-positive enhancer region in the first intron of the FBP1 gene (Fig.?4E).Importantly, we found that at the same region there is a peak of histone H3 lysine-27 acetylation (H3K27Ac) (Fig.?4E), the level of which often correlates with transcriptional activity of the gene. We first examined whether treatment of the HDAC inhibitor NaBu affects H3K27Ac levels in this region. To this end, we erformed chromatin immunoprecipitation (ChIP) assays using H3K27Ac-specific antibody. As demonstrated in Fig.?4F, the H3K27Ac level was readily detectable in the enhancer region of FBP1 gene in both HepG2 and SK-Hep1 cell lines.However, consistent with the finding that NaBu treatment markedly increased expression of FBP1 mRNA (Fig.?2A), it also significantly increased H3K27Ac level in the FBP1 enhancer (Fig.?4F). Similar to the finding that HDAC1 and HDAC2 knockdown induced FBP1 expression, depletion of these proteins alone or together also largely increased H3K27Ac level at this locus (Fig.?4G). This data indicate that the FBP1 gene locus indeed harbors a regulatory region where H3K27Ac level can be modulated by HDAC proteins. Thus, HDAC inhibitor-induced upregulation of H3K27 acetylation in the enhancer of the FBP1 gene correlates with increased expression of FBP1 induced by HDAC inhibitors.;We noticed that there is a putative H3K4me1-positive enhancer region in the first intron of the FBP1 gene (Fig.?4E).Importantly, we found that at the same region there is a peak of histone H3 lysine-27 acetylation (H3K27Ac) (Fig.?4E), the level of which often correlates with transcriptional activity of the gene. We first examined whether treatment of the HDAC inhibitor NaBu affects H3K27Ac levels in this region. To this end, we erformed chromatin immunoprecipitation (ChIP) assays using H3K27Ac-specific antibody. As demonstrated in Fig.?4F, the H3K27Ac level was readily detectable in the enhancer region of FBP1 gene in both HepG2 and SK-Hep1 cell lines.However, consistent with the finding that NaBu treatment markedly increased expression of FBP1 mRNA (Fig.?2A), it also significantly increased H3K27Ac level in the FBP1 enhancer (Fig.?4F). Similar to the finding that HDAC1 and HDAC2 knockdown induced FBP1 expression, depletion of these proteins alone or together also largely increased H3K27Ac level at this locus (Fig.?4G). This data indicate that the FBP1 gene locus indeed harbors a regulatory region where H3K27Ac level can be modulated by HDAC proteins. Thus, HDAC inhibitor-induced upregulation of H3K27 acetylation in the enhancer of the FBP1 gene correlates with increased expression of FBP1 induced by HDAC inhibitors. --;--;-- 28262751 chr4 97123309 97712957 SMARCB1 Of these subunits, several core members are present in most or all SWI/SNF complexes, including SMARCB1 (also known as SNF5, BAF47 and INI1), SMARCC1/SMARCC2 (also known as BAF155 and BAF170), and one of the two mutually exclusive ATPase subunits, SMARCA4 (also known as BRG1) and SMARCA2 (also known as BRM), which utilize energy derived from ATP hydrolysis to mobilize nucleosomes2,3. human Low+High throughput The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers. 否 Malignancies mouse embryonic fibroblast cell E_02_0805 ChIP-seq Following inactivation of either Smarcb1 or Smarca4, we observed little change in H3K27ac levels at promoters, but a marked reduction at many enhancers (Fig. 1b,c). This reduction at enhancers was robust and consistent across replicate experiments performed on MEFs derived from independent mice (Methods, Supplementary Figs 3-7). Enhancer -- ChIP-seq,Western blot 1110047K16Rik,9430022M17Rik,CTF,NF1-A,NF1A -- -- -- A430090G16,A730011L11,KAT3B,p300,p300 HAT ChIP-seq -- -- Nfia,Nfia,Nfia,Nfia Ep300,Ep300,Ep300,Ep300 To investigate whether SWI/SNF is acting directly at active enhancers, we performed ChIP-Seq for the core SWI/SNF subunits SMARCC1 and SMARCA4 in wild-type and Smarcb1-deficient cells. Because the genome-wide binding profiles of these two subunits were very similar (Supplementary Fig. 3), we considered the average of the two experiments to be representative of SWI/SNF binding for each condition. Interestingly, we found that SWI/SNF was bound at the vast majority of enhancers in wild-type cells-over 95% of enhancers showed enrichment (IP>input; Fig. 2a and Supplementary Fig. 9a). Deletion of the Smarcb1 subunit led to a widespread reduction in SWI/SNF binding (Fig. 2b and Supplementary Fig. 9b).Taken together, the targeting of SWI/SNF to enhancers and the association between loss of SWI/SNF binding and the loss of H3K27ac suggests a direct role for the SWI/SNF complex in regulating the enhancer chromatin landscape in MEFs.;To investigate whether SWI/SNF is acting directly at active enhancers, we performed ChIP-Seq for the core SWI/SNF subunits SMARCC1 and SMARCA4 in wild-type and Smarcb1-deficient cells. Because the genome-wide binding profiles of these two subunits were very similar (Supplementary Fig. 3), we considered the average of the two experiments to be representative of SWI/SNF binding for each condition. Interestingly, we found that SWI/SNF was bound at the vast majority of enhancers in wild-type cells-over 95% of enhancers showed enrichment (IP>input; Fig. 2a and Supplementary Fig. 9a). Deletion of the Smarcb1 subunit led to a widespread reduction in SWI/SNF binding (Fig. 2b and Supplementary Fig. 9b).Taken together, the targeting of SWI/SNF to enhancers and the association between loss of SWI/SNF binding and the loss of H3K27ac suggests a direct role for the SWI/SNF complex in regulating the enhancer chromatin landscape in MEFs.;To investigate whether SWI/SNF is acting directly at active enhancers, we performed ChIP-Seq for the core SWI/SNF subunits SMARCC1 and SMARCA4 in wild-type and Smarcb1-deficient cells. Because the genome-wide binding profiles of these two subunits were very similar (Supplementary Fig. 3), we considered the average of the two experiments to be representative of SWI/SNF binding for each condition. Interestingly, we found that SWI/SNF was bound at the vast majority of enhancers in wild-type cells-over 95% of enhancers showed enrichment (IP>input; Fig. 2a and Supplementary Fig. 9a). Deletion of the Smarcb1 subunit led to a widespread reduction in SWI/SNF binding (Fig. 2b and Supplementary Fig. 9b).Taken together, the targeting of SWI/SNF to enhancers and the association between loss of SWI/SNF binding and the loss of H3K27ac suggests a direct role for the SWI/SNF complex in regulating the enhancer chromatin landscape in MEFs.;To investigate whether SWI/SNF is acting directly at active enhancers, we performed ChIP-Seq for the core SWI/SNF subunits SMARCC1 and SMARCA4 in wild-type and Smarcb1-deficient cells. Because the genome-wide binding profiles of these two subunits were very similar (Supplementary Fig. 3), we considered the average of the two experiments to be representative of SWI/SNF binding for each condition. Interestingly, we found that SWI/SNF was bound at the vast majority of enhancers in wild-type cells-over 95% of enhancers showed enrichment (IP>input; Fig. 2a and Supplementary Fig. 9a). Deletion of the Smarcb1 subunit led to a widespread reduction in SWI/SNF binding (Fig. 2b and Supplementary Fig. 9b).Taken together, the targeting of SWI/SNF to enhancers and the association between loss of SWI/SNF binding and the loss of H3K27ac suggests a direct role for the SWI/SNF complex in regulating the enhancer chromatin landscape in MEFs. To further evaluate how the interaction between SWI/SNF and p300 regulates H3K27ac levels, we immunoprecipitated SWI/SNF complexes using an antibody against the core subunit SMARCC1 and measured histone acetylation activity using recombinant histones as a substrate. With immunoprecipitated SWI/SNF complexes from a RT cell line that lacked SMARCB1, the sample lacked acetyltransferase activity. However, re-expression of SMARCB1 increased H3K27-specific acetyltransferase activity, despite acetylation of H3K9ac being not significantly changed, suggesting the presence of H3K27-specific acetylation activity (Fig. 3d). ;To further evaluate how the interaction between SWI/SNF and p300 regulates H3K27ac levels, we immunoprecipitated SWI/SNF complexes using an antibody against the core subunit SMARCC1 and measured histone acetylation activity using recombinant histones as a substrate. With immunoprecipitated SWI/SNF complexes from a RT cell line that lacked SMARCB1, the sample lacked acetyltransferase activity. However, re-expression of SMARCB1 increased H3K27-specific acetyltransferase activity, despite acetylation of H3K9ac being not significantly changed, suggesting the presence of H3K27-specific acetylation activity (Fig. 3d). ;To further evaluate how the interaction between SWI/SNF and p300 regulates H3K27ac levels, we immunoprecipitated SWI/SNF complexes using an antibody against the core subunit SMARCC1 and measured histone acetylation activity using recombinant histones as a substrate. With immunoprecipitated SWI/SNF complexes from a RT cell line that lacked SMARCB1, the sample lacked acetyltransferase activity. However, re-expression of SMARCB1 increased H3K27-specific acetyltransferase activity, despite acetylation of H3K9ac being not significantly changed, suggesting the presence of H3K27-specific acetylation activity (Fig. 3d). ;To further evaluate how the interaction between SWI/SNF and p300 regulates H3K27ac levels, we immunoprecipitated SWI/SNF complexes using an antibody against the core subunit SMARCC1 and measured histone acetylation activity using recombinant histones as a substrate. With immunoprecipitated SWI/SNF complexes from a RT cell line that lacked SMARCB1, the sample lacked acetyltransferase activity. However, re-expression of SMARCB1 increased H3K27-specific acetyltransferase activity, despite acetylation of H3K9ac being not significantly changed, suggesting the presence of H3K27-specific acetylation activity (Fig. 3d). 28260788 chr11 8240851 8242851 LMO1 APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL. human lymph Low+High throughput APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL 否 -- RPMI-8402 cell E_02_0806 ChIP-seq,Luciferase Reporter Assay,ChIA-PET To identify mutations in the T-ALL genome that might signi?cantly alter oncogene expression, we focused our search on aberrant,sample-speci?c enhancers in 10 different human T-ALL cell lines as identi?ed by H3K27ac ChIP-seq. The aberrant active enhancer we identi?ed was present upstream of the LMO1 gene in RPMI-8402 and Jurkat T-ALL cell lines. To ascertain whether this single base-pair substitution can activate LMO1 gene expression, we cloned a 585-bp genomic DNA fragment from either the C allele or T allele upstream of luciferase and tested the enhancer activity of this fragment in a reporter assay.When introduced into Jurkat cells, the construct containing the T allele exhibited robust reporter activity, which was four-fold greater than that of the fragment containing the C allele (Figure 3f).Taken together, we have shown that the somatically acquired C-to-T mutation that creates a MYB binding motif ~ 4 kb upstream of the proximal transcription start site of LMO1 in T-ALL can generate an active transcriptional enhancer that drives monoallelic overexpression of the LMO1 oncogene. We also used chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) 24 in Jurkat cells to demonstrate that the stream of the proximal LMO1 transcription start site used by Jurkat cells (Figure 5d and Supplementary Figure S1), indicating that the active enhancer mediated by the acquired MYB binding motif loops to the LMO1 gene promoter region to regulate the transcription of LMO1 (Figure 5e). Enhancer -- Luciferase Reporter Assay RBTN1,RHOM1,TTG1 -- -- -- Cmyb, c-myb, c-myb_CDS, efg ChIP-seq -- -- LMO1 MYB To ascertain whether this single base-pair substitution can activate LMO1 gene expression, we cloned a 585-bp genomic DNA fragment from either the C allele or T allele upstream of luciferase and tested the enhancer activity of this fragment in a reporter assay.When introduced into Jurkat cells, the construct containing the T allele exhibited robust reporter activity, which was four-fold greater than that of the fragment containing the C allele (Figure 3f).Taken together, we have shown that the somatically acquired C-to-T mutation that creates a MYB binding motif ~ 4 kb upstream of the proximal transcription start site of LMO1 in T-ALL can generate an active transcriptional enhancer that drives monoallelic overexpression of the LMO1 oncogene. Analysis of the genomic sequences of both C and T alleles, using UniPROBE and HOCOMOCO databases, identi?ed a de novo-binding motif for the MYB transcription factor (Figure 3a and Supplementary Table S3), while analysis of the MYB and H3K27ac ChIP-seq DNA sequence reads aligned with this site demon-strated that MYB and H3K27ac were bound almost exclusively by the T allele (Figure 3b).Knockdown of MYB expression using lentivirus-transduced shRNA decreased the expression of LMO1 signi?cantly in Jurkat cells (Figure 3d), indicating that MYB binding to the somatically acquired heterozygous MYB binding motif leads to enhanced expression of LMO1 in T-ALL from the same allele. 28244015 chr3 181572712 181574712 SOX2 These findings suggest that physiological levels of BPA increase estrogen receptor-positive breast cancer tumor maintenance through enhanced cancer stem-like cell activity via direct regulation of SOX2 transcription. human breast Low throughput Bisphenol A Induces Sox2 in ER + Breast Cancer Stem-Like Cells 否 -- MCF-7 cell E_02_0807 ChIP,qPCR To determine whether BPA-activated pCREB directly regulates SOX2 , ChIP was performed after a 5-minute treatment with either E2 or BPA. pCREB was enriched at an Enhancer region located 143 kilobases downstream of the SOX2 coding region only after BPA treatment (Figure 6), which correlates with gene expression Enhancer -- ChIP,qPCR ANOP3, MCOPS3 -- -- -- BP240,BPA,BPAG1,CATX-15,CATX15,D6S1101,DMH,DT,EBSB2,HSAN6,MACF2 ChIP -- -- SOX2 DST To determine whether BPA-activated pCREB directly regulates SOX2 , ChIP was performed after a 5-minute treatment with either E2 or BPA. pCREB was enriched at an Enhancer region located 143 kilobases downstream of the SOX2 coding region only after BPA treatment (Figure 6), which correlates with gene expression To determine whether BPA-activated pCREB directly regulates SOX2, ChIP was performed after a 5-minute treatment with either E2 or BPA. pCREB was enriched at an Enhancer region located 143 kilobases downstream of the SOX2 coding region only after BPA treatment (Figure 6), which correlates with gene expression. 28213503 chr11 44386118 44393090 STAT3 The receptor for IL-10 activates STAT3 through a JAK1 dependent pathway (12). In most systems STAT3 is a transcriptional activator and there is little evidence that STAT3 has direct inhibitory function or binds to regulatory regions of IL-10-inhibited genes (13). human Low+High throughput Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation. 否 Inflammatory Disease macrophage E_02_0808 ChIP-seq However, following treatment with acute IL-10, H3K27ac was significantly lower at peaks associated with genes from Cluster 2 than at peaks associated with genes from Cluster 1 (p-value <0.01 by Mann-Whitney test, Fig. 6A). Examples of Cluster 1 and Cluster 2 enhancers are shown in Fig. 6B and Fig. 6C, respectively. Interestingly this analysis identified a peak inhibited by acute IL-10 that encompasses a DNAse hypersensitivity site 10 kb upstream of Il12b that has previously been demonstrated in a reporter assay to exhibit enhancer activity (Fig. 6C). Enhancer -- ChIP-seq,RT-PCR CINC-2a,GROb,Gro2,MIP-2,MIP-2a,Mgsa-b,Mip2,Scyb,Scyb2 -- -- -- 1110034C02Rik, AW109958, Aprf ChIP-seq -- -- Cxcl2,Cxcl2 Stat3,Stat3 To evaluate this issue, we compared induction of Cxcl2 transcription in IL-10-deficient macrophages stimulated with LPS alone, both LPS and IL-10, or stimulated with IL-10 for 1 hour prior to stimulation with LPS. As predicted, LPS rapidly induced Cxcl2 pre-mRNA within 1h hour of stimulation. Surprisingly, addition of IL-10 at the time of LPS stimulation or addition 1 hour prior to LPS stimulation had little influence on Cxcl2 pre-mRNA at 1h post LPS stimulation, although significant suppression was observed at 2h post LPS stimulation (Fig. 8A). ;To evaluate this issue, we compared induction of Cxcl2 transcription in IL-10-deficient macrophages stimulated with LPS alone, both LPS and IL-10, or stimulated with IL-10 for 1 hour prior to stimulation with LPS. As predicted, LPS rapidly induced Cxcl2 pre-mRNA within 1h hour of stimulation. Surprisingly, addition of IL-10 at the time of LPS stimulation or addition 1 hour prior to LPS stimulation had little influence on Cxcl2 pre-mRNA at 1h post LPS stimulation, although significant suppression was observed at 2h post LPS stimulation (Fig. 8A). To address this possibility, we performed ChIP-seq with an anti-STAT3 antibody to identify STAT3 binding sites.Interestingly, virtually all identified STAT3 binding sites were located within H3K4me1 peaks, suggesting that STAT3 binds to enhancers. As anticipated, we found strong STAT3 binding near Cluster 3 genes induced by IL-10, such as Socs3 (Fig. 7, bottom left), and IL-10 induced an increase in average mean acetylation at STAT3 binding sites associated with genes in Cluster 3, consistent with enhancer activation (Fig. 7, bottom right).;To address this possibility, we performed ChIP-seq with an anti-STAT3 antibody to identify STAT3 binding sites.Interestingly, virtually all identified STAT3 binding sites were located within H3K4me1 peaks, suggesting that STAT3 binds to enhancers. As anticipated, we found strong STAT3 binding near Cluster 3 genes induced by IL-10, such as Socs3 (Fig. 7, bottom left), and IL-10 induced an increase in average mean acetylation at STAT3 binding sites associated with genes in Cluster 3, consistent with enhancer activation (Fig. 7, bottom right). 28123038 chrX 55054584 55054678 ALAS2 However, compared with the int-8-GATA site, the int-1-GATA site is more essential for regulating ALAS2 expression through CRISPR/Cas9-mediated site-specific deletion. human bone marrow Low throughput Intron 1 GATA site enhances ALAS2 expression indispensably during erythroid differentiation 否 -- K-562 CELL E_02_0809 3C,Luciferase Reporter Assay,RT-qPCR,CRISPR/Cas9 A luciferase reporter assay conirmed the enhancer activity of this GATA site in vitro (Figure 1E). Furthermore, the physical proximity between the int-1-GATA and int-8-GATA sites and between the promoter and the int-8-GATA site were veriied by 3C assays (Figure 4H and I), suggesting that the promoter, the int-1-GATA site and the int-8-GATA site could form a potential chromatin enhancer loop. To further interrogate the speciic role of proximal int-1-GATA and distal int-8-GATA enhancer elements in ALAS2 regulation, we employed CRISPR/Cas9 technol-ogy to separately delete the GATA1 binding sites from the intron 1 or 8 enhancer regions in K562 cells.As expected,GATA site deletion in int1 6 and int8 4 cells entirely disrupted GATA1 occupancy at the intron 1 and 8 enhancer regions, respectively, whereas each deletion did not affect GATA1 occupancy at the other intronic GATA site and the promoter region (Figure 7C). We detected signiicant reductions in ALAS2 expression in both int1 6 and int8 4 cells during cytosine arabinoside (AraC)-inducedK562 erythroid differentiation (Fig-Nucleic Acids Research, 2017, Vol. 45, No. 2 667 ure 7D and E). Enhancer 3C,CRISPR/Cas9 Luciferase Reporter Assay,RT-qPCR ALAS-E,ALASE,ANH1,ASB,SIDBA1,XLDPP,XLEPP,XLSA -- -- -- ERYF1,GATA-1,GF-1,GF1,NF-E1,NFE1,XLANP,XLTDA,XLTT ChIP-qPCR -- -- ALAS2 GATA1 A luciferase reporter assay conirmed the enhancer activity of this GATA site in vitro (Figure 1E). Furthermore, the physical proximity between the int-1-GATA and int-8-GATA sites and between the promoter and the int-8-GATA site were veriied by 3C assays (Figure 4H and I), suggesting that the promoter, the int-1-GATA site and the int-8-GATA site could form a potential chromatin enhancer loop. To further interrogate the speciic role of proximal int-1-GATA and distal int-8-GATA enhancer elements in ALAS2 regulation, we employed CRISPR/Cas9 technol-ogy to separately delete the GATA1 binding sites from the intron 1 or 8 enhancer regions in K562 cells.As expected,GATA site deletion in int1 6 and int8 4 cells entirely disrupted GATA1 occupancy at the intron 1 and 8 enhancer regions, respectively, whereas each deletion did not affect GATA1 occupancy at the other intronic GATA site and the promoter region (Figure 7C). We detected signiicant reductions in ALAS2 expression in both int1 6 and int8 4 cells during cytosine arabinoside (AraC)-inducedK562 erythroid differentiation (Fig-Nucleic Acids Research, 2017, Vol. 45, No. 2 667 ure 7D and E). The ChIP-qPCR assay showed the binding of GATA1 to the promoter and the intron 1 and 8 enhancer regions in int1_x0002_6, int8_x0002_4 and WT K562 cells. The DNA sequence at the exon 4-intron 4 junction (exon 4/intron 4) acts as a negative control region. Normal rabbit IgG was employed as the control in all ChIP assays. 28121289 chr6 88202011 88204330 SUN1 Although this mouse line was reported to be normal, SUN1 overexpression potentially could affect cell phenotype and gene regulation (Chen et al., 2012). human Low+High throughput Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq. 否 -- Endothelial stalk cell E_02_0810 Luciferase Reporter Assay,ChIP-seq,Western blot Viewing Ep300fb bioChiP-seq signal at genes selectively expressed in heart or brain confirmed robust tissue-specific differences that overlapped enhancers with known tissue-specific activity.To further functionally validate the transcriptional activity of these heterodimer motifs, we measured their enhancer activity using luciferase reporter assays. Enhancer -- Luciferase Reporter Assay,ChIP-seq Gata-2 -- -- -- A430090G16,A730011L11,KAT3B,p300,p300 HAT ChIP-seq -- -- Gata2 Ep300 At the skeletal muscle specific gene Myod, Myf5Cre drove strong Ep300fb bioChiP-seq signal at a known distal Enhancer (Goldhamer et al., 1992), as well as a second Ep300 bound region about 12 kb upstream from the transcriptional start site. However, antibodies for Ep300 are marginal for robust ChIP-seq, particularly from tissues, leading to low reproducibility, variation between antibody lots, and inefficient Enhancer identification. 28104492 chr15 97898854 97902854 CYP24A1 Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12V) significantly reduced 1,25(OH)2D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. However, chromatin accessibility to the VDR gene at the proximal promoter ( 300 bp), an enhancer region at 6 kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). human Low throughput Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression. 否 Colon Cancer YAMC Cell E_02_0811 Luciferase Reporter Assay,Western blot,DNaseI-seq Zella et al. [22] found that transcription of the mouse VDR gene is regulated at seven promoter and enhancer regions (Fig. 5A) in the mouse osteoblast cell line MC3T3-E1. In addition, the ENCODE project has identified DNAse I hypersensitive sites in the mouse large intestine that overlap with these regions. Enhancer -- Luciferase Reporter Assay,Western blot Nr1i1 -- -- -- -- -- -- -- Vdr,Vdr --,-- However, chromatin accessibility to the VDR gene at the proximal promoter (_x0001_300 bp), an Enhancer region at _x0001_6 kb, and an Enhancer region located in exon 7 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS).;However, chromatin accessibility to the VDR gene at the proximal promoter (_x0001_300 bp), an Enhancer region at _x0001_6 kb, and an Enhancer region located in exon 7 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). --;-- 28087634 chr2 105072843 105076843 SOX9 SRY and SOX9 control the differentiation of Sertoli cells by triggering a dramatic transcriptional reprogramming of bipotential progenitor cells within just 24 h, leading to the upregulation of over 200 genes important for Sertoli cell development and downregulation of 100 pregranulosa cell-expressed genes that were expressed at the bipotential stage (Munger et al., 2013). human Low+High throughput Genome-wide identification of regulatory elements in Sertoli cells. 否 Genitourinary Defects Sustentacular cell E_02_0812 ChIP-seq,DNaseI-seq H3K27ac ChIP-seq on E13.5 Sertoli cells identified >28,000 H3K27ac peaks, ?70% of which overlapped a DHS in our E13.5 Sertoli cell dataset (Fig. 3A, Fig. S4).H3K27ac-positive DHSs, which are indicative of active enhancers, were significantly enriched specifically in neighboring Sertoli cell-expressed genes (Fig. 3D), as expected. Enhancer -- ChIP-seq,DNaseI-seq D630046I19Rik,Wt-1 -- -- -- -- -- -- -- Wt1 ,Wt1 --,-- To demonstrate this, we performed a transient transgenic assay with a putative active enhancer of the Wt1 gene (Fig. 5A,B).We identified a DHS peak located 50?kb upstream of Wt1 that was unique to E13.5 and E15.5 Sertoli cells compared with the other cell types we examined, and marked by H3K27ac, suggesting that it functions as an active enhancer.;To demonstrate this, we performed a transient transgenic assay with a putative active enhancer of the Wt1 gene (Fig. 5A,B).We identified a DHS peak located 50?kb upstream of Wt1 that was unique to E13.5 and E15.5 Sertoli cells compared with the other cell types we examined, and marked by H3K27ac, suggesting that it functions as an active enhancer. --;-- 28082341 chr3 46988575 46990242 GATA1 In conclusion, we herein show a long-distance regulatory region with GATA1 binding sites as being a strong enhancer for NBEAL2 expression. human bone marrow Low throughput The transcription factor GATA1 regulates NBEAL2 expression through a long-distance enhancer 否 -- K-562 CELL E_02_0813 Luciferase Reporter Assay,ChIP,RT-PCR Chromatin immunoprecipitation sequencing revealed 5 GATA binding sites in a regulatory region 31 kb upstream of NBEAL2 covered by a H3K4Me1 mark indicative of an Enhancer locus.Luciferase reporter constructs containing this region confirmed its Enhancer activity in K562 cells, and mutagenesis of the GATA1 binding sites resulted in significantly reduced Enhancer activity. Enhancer -- Luciferase Reporter Assay,ChIP,RT-PCR BDPLT4,GPS -- -- -- ERYF1,GATA-1,GF-1,GF1,NF-E1,NFE1,XLANP,XLTDA,XLTT Immunoblot -- -- NBEAL2 GATA1 Chromatin immunoprecipitation sequencing revealed 5 GATA binding sites in a regulatory region 31 kb upstream of NBEAL2 covered by a H3K4Me1 mark indicative of an Enhancer locus.Luciferase reporter constructs containing this region confirmed its Enhancer activity in K562 cells, and mutagenesis of the GATA1 binding sites resulted in significantly reduced Enhancer activity. Immunoblot analysis for NBEAL2 with a rabbit polyclonal antibody and integrin β3 were performed (left) using total protein MK lysates at days 8 and 11 for the control and day 11 for GATA1 D218Y (right) using total protein MK lysates at day 13 for the control and GATA1 D218G. 28045957 chr11 112769210 112772210 Sox9 Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly. mouse connective Low throughput Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone 否 -- Testis somatic cell E_02_0814 Transgenic mice,CRISPR/Cas9,qRT-PCR During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Enhancer -- qRT-PCR 2010306G03Rik,AV220920,mKIAA4243 reduced expression of the SOX9 target Amh. CRISPR/Cas9 Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. -- -- -- -- Sox9 ,Sox9 --,-- These results of qRT-PCR clearly indicate that the TESCO Enhancer is an important regulator of Sox9 expression throughout testis development, accounting for around 40% of its expression levels.;These results of qRT-PCR clearly indicate that the TESCO Enhancer is an important regulator of Sox9 expression throughout testis development, accounting for around 40% of its expression levels. --;-- 27989796 chr17 69541883 69542989 SOX9 SR4 activity and the observed SOX9 expression pattern suggest that SR4 may function as a Sox9 genital tubercle enhancer. human testis Low throughput Altered SOX9 genital tubercle enhancer region in hypospadias 否 Disorders Of Sexual Development TM4 cell E_02_0815 Luciferase Reporter Assay,PCR,Transgenic mice,Immunofluorescence Our previous work involving the genomic analysis of isolated DSD patients revealed a 78 kb minimal sex determining region (RevSex) far upstream of SOX9 that was duplicated in 46,XX and deleted in 46,XY DSDs. It was postulated that RevSex contains a gonadal enhancer. However, the most highly conserved sub-region within RevSex, called SR4, was neither responsive to sex determining factors in vitro nor active in the gonads of transgenic mice, suggesting that SR4 may not be functioning as a testicular enhancer. Interestingly, SR4 transgenic mice showed reporter activity in the genital tubercle, the primordium of the penis and clitoris, a previously unreported domain of Sox9 expression. SOX9 protein was detected in the genital tubercle, notably in the urethral plate epithelium, preputial glands, ventral surface ectoderm and corpus cavernosa. SR4 may therefore function as a Sox9 genital tubercle enhancer, mutations of which could possibly lead to hypospadias, a birth defect seen in the DSD patients in the RevSex study. SR4 activity and the observed SOX9 expression pattern suggest that SR4 may function as a Sox9 genital tubercle enhancer. However, conditional ablation of Sox9 in the genital tubercle using Shh-Cre/+;Sox9flox/flox mice revealed no genital tubercle abnormalities, possibly due to compensation by similar Sox factors. To conclude, we have identified a novel regulatory enhancer driving Sox9 expression during external genitalia development. Enhancer -- Transgenic mice,Immunofluorescence CMD1,CMPD1,SRA1,SRXX2,SRXY10 -- -- -- CMD1,CMPD1,SRA1,SRXX2,SRXY10 Luciferase Reporter Assay -- -- SOX9 SOX9 The transcriptional activity of the SR4 enhancer in the genital tubercle led us to investigate whether SOX9 protein was also expressed there. Immunofluorescence using a SOX9 antibody on genital tubercle sections from E15.5 mouse embryos was performed (Fig. 5). SOX9 was detected in the genital tubercle of both sexes, specifically in the preputial glands, the urethral plate epithelium, ventral surface ectoderm and the corpus cavernosa. SR4 and TESC luciferase constructs containing an E1b minimal promoter, as well as the empty E1b-Luc vector, were transiently co-transfected into TM4 cells with expression plasmids bearing SF-1 and SRY, or SF-1 and SOX9. While activation of the TESCO enhancer was observed in luciferase assays, SR4 was not activated by the transcription factors tested. Data are represented in the form of relative luciferase activity. 27986456 chr18 69656860 69683465 TCF4 We report that TCF4 comprises two transcriptional isoforms, both of which are required for optimal pDC development in vitro. The long Tcf4 isoform is expressed specifically in pDCs, and its deletion in mice impaired pDCs development and led to the expansion of non-canonical CD8 cDCs. The expression of Tcf4 commenced in progenitors and was further upregulated in pDCs, correlating with stage-specific activity of multiple enhancer elements. A conserved enhancer downstream of Tcf4 was required for its upregulation during pDC differentiation, revealing a positive feedback loop. The expression of Tcf4 and the resulting pDC differentiation were selectively sensitive to the inhibition of enhancer-binding BET protein activity. Thus, lineage-specifying function of E proteins is facilitated by lineage-specific isoform expression and by BET-dependent feedback regulation through distal regulatory elements. human connective Low+High throughput Isoform-Specific Expression and Feedback Regulation of E Protein TCF4 Control Dendritic Cell Lineage Specification 否 -- HoxB8-FL cell E_02_0816 ATAC-seq ATAC-Seq analysis of Tcf4 locus in primary DCs. Shown are ATAC-Seq peaks across ~1.5 Mb of the Tcf4 locus; indicated are proximal promoters of Tcf4L (green) and Tcf4S (purple), the 3′ enhancer (orange) and the cluster of 5′ regulatory elements (yellow). In this and subsequent panels, the scale was adjusted between different samples based on signals from housekeeping genes.We analyzed the 3′ region by ChIP during the differentiation of HoxB8-FL cells. Histone modifications associated with active enhancers, including histone 3 lysine 4 monomethylation (H3K4me1) and lysine 27 acetylation (H3K27ac), were induced in this region on day 4, i.e. at the onset of pDC differentiation (Fig. 5D). Super-Enhancer CRISPR/Cas9 ChIP-seq,ATAC-seq 5730422P05Rik,ASPI2,E2-2,E2.2,ITF-2,ITF-2b,ITF2,ME2,MITF-2A,MITF-2B,SEF-2,SEF2,SEF2-1,TFE,Tcf-4,bHLHb19 A conserved Enhancer downstream of Tcf4 was required for its upregulation during pDC differentiation, revealing a positive feedback loop qRT-PCR,CRISPR/Cas9 By qRT-PCR, Tcf4S was prominently expressed in pDCs but also present in other cell types including B cells and cDCs 5730422P05Rik,ASPI2,E2-2,E2.2,ITF-2,ITF-2b,ITF2,ME2,MITF-2A,MITF-2B,SEF-2,SEF2,SEF2-1,TFE,Tcf-4,bHLHb19 qRT-PCR -- -- Tcf4 Tcf4 ChIP analysis of histone modifications (H3K4me1 and H3K27ac) and of TCF4 binding to the 3′ Enhancer in differentiating HoxB8-FL cells. By qRT-PCR, Tcf4S was prominently expressed in pDCs but also present in other cell types including B cells and cDCs. 27980063 chr1 24601612 24626812 GRHL3 Together, our findings support a function for BRD4 in promoting basal mammary cell epithelial differentiation, at least in part, by regulating FOXO factor function on enhancers to activate TP63 and GRHL3 expression. human Low+High throughput BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells 否 Breast Cancer B cell E_02_0817 ChIP-seq,Western blot ChIP analyses of BRD4 and RNAPII occupancy revealed that decreased BRD4 occupanc on enhancers in response to JQ1 or OTX015 treatment leads to a signiicant concomitant reduction in RNAPII occupancy on these regions (Figure 4H, I and K, L). While BRD4 occupancy was not significantly affected around the Np63 TSS, the potential enhancers displayed a substantial reduction in the occupancy of both BRD4 and RNAPII (Figure 4HandI). Most importantly, BRD4 inhibition resulted in the down regulation of the putative TP63-- and GRHL3--associated eRNAs (Figure 4J and N). Enhancer -- ChIP SOM,TFCP2L4,VWS2 This Enhancer is located in a region where a long-range chromatin interaction among the promoters and promoter-Enhancer of several genes has been described, possibly affecting their expression simultaneously. Luciferase Reporter Assay In the present work, by integrating several strategies, we have uncovered the variant most strongly associated with MS in the region. This variant also affects the activity of an Enhancer in an allele-dependent and orientation-dependent manner and correlates with the expression of five genes of the locus. FOXO,SOM,TFCP2L4,VWS2 Western blot -- -- GRHL3 FOXO,GRHL3 ChIP analyses of BRD4 and RNAPII occupancy revealed that decreased BRD4 occupanc on enhancers in response to JQ1 or OTX015 treatment leads to a significant concomitant reduction in RNAPII occupancy on these regions (Figure 4H, I and K, L).Altogether, these studies demonstrate an enhancer--associated function of BRD4 in modulating the expression of TP63 and GRHL3. Western blot analyses of MCF10A protein ysates showing total p63 and GRHL3 expression with 100 nM and 1 _x0002_M of FOXO1 inhibitor AS1842856 (FOXO1i) for 24 h after removal of EGF and Insulin (-EGF/-Ins) for 48 h. 27941798 chr15 63833002 63863200 ARID1A These tumors lack deregulation of APC/β-catenin signaling components, which are crucial gatekeepers in common forms of intestinal cancer. We find that ARID1A normally targets SWI/SNF complexes to enhancers, where they function in coordination with transcription factors to facilitate gene activation. ARID1B preserves SWI/SNF function in ARID1A-deficient cells, but defects in SWI/SNF targeting and control of enhancer activity cause extensive dysregulation of gene expression. These findings represent an advance in colon cancer modeling and implicate enhancer-mediated gene regulation as a principal tumor-suppressor function of ARID1A. human connective Low+High throughput ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice 否 Colon Cancer HCT116 cell E_02_0818 ChIP-seq To determine if control of enhancer activity by SWI/SNF complexes is coordinated with TFs, we analyzed sequence motifs at enhancers sensitive to ARID1A loss. The CTCF motif was relatively depleted in regions of H3K27ac loss, implying CTCF-bound insulator regions may resist modulation, while the AP1 (JUND/FOSL1) motif was most enriched (Fig. 5a, Supplementary Table 5).Among factors assessed in HCT116 cells, binding of these TFs correlated most strongly with SWI/SNF occupancy (Supplementary Fig. 6b) and was higher at enhancers that lost activity than at enhancers that were unaffected by ARID1A deficiency (Fig. 5c). Super-Enhancer -- ChIP-seq,ChIP-qPCR 1110030E03Rik, BAF250a, Osa1, Smarcf1 -- -- -- AP-1c,c-jun,Jun,C/EBPbeta,CRP2,IL-6DBP,LAP,LIP,NF-IL6,NF-M,Nfil6 ChIP-seq -- -- Arid1a Jun,Cebpb To determine if ARID1A loss impairs enhancer activity?in vivo, we examined H3K27ac and gene expression in the colonic epithelium of wildtype and Villin-CreER-T2?Arid1afl/fl?mice. Again, whereas promoter activation states were changed little (Fig. 5d), the effects on H3K27ac at enhancers were significant and were correlated with changes in mRNA levels of the nearest genes (Fig. 5e).? ChIP-Seq profiles for HCT116 cells, including those generated by ENCODE21 (Encyclopedia of DNA Elements, Supplementary Table 6), revealed further that H3K27ac loss was most strongly associated with sites bound in WT cells by SWI/SNF complexes and/or TFs including AP1, CEBPB, and TEAD4 (Fig. 5b). Among factors assessed in HCT116 cells, binding of these TFs correlated most strongly with SWI/SNF occupancy (Supplementary Fig. 6b) and was higher at enhancers that lost activity than at enhancers that were unaffected by ARID1A deficiency (Fig. 5c) 27920250 chr5 137465620 137479420 Epo We prepared various Epo gene-reporter constructs utilizing a bacterial artificial chromosome and generated a number of transgenic-mouse lines. We observed that deletion of the CURE region (δCURE) abrogated Epo gene expression in REP cells. Although transgenic expression of the δCURE construct rescued Epo-deficient mice from embryonic lethality, the rescued mice had severe EPO-dependent anemia. These mouse lines serve as an elaborate model for the search for erythroid stimulatory activity and are referred to as AnRED (anemic model with renal EPO deficiency) mice. We also dissected the CURE region by exploiting a minigene harboring four phylogenetically conserved elements in reporter transgenic-mouse analyses. Our analyses revealed that Epo gene regulation in REP cells is a complex process that utilizes multiple regulatory influences. mouse epithelial Low throughput Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements 否 Renal Anemia Nephrocyte E_02_0819 Luciferase Reporter Assay,Transgenic mice 17k-GFP contains the 17-kb upstream and 15-kb downstream regions, whereas 17kXM-GFP contains only the 17-kb upstream region as a regulatory element. As in 22k-GFP mice, GFP expression was observed in the kidney and liver in 17k-GFP mice under anemic conditions (Fig. 1C). Enhancer -- Luciferase Reporter Assay,qRT-PCR Epo -- -- -- -- -- -- -- Epo -- we generated a series of transgenic GFP reporter constructs using 60k-GFP and 22k-GFP as the starting materia GFP expression was observed in the kidney but not in the liver in 17kXM-GFP mice.By means of long genomic PCR assays utilizing a primer set recognizing sequences located 18.6 kb upstream (forward primer) and 3.7 kb downstream (reverse primer) from the Epo gene transcription start site, we confirmed that the bulk of the Epo-BAC DNA containing a 17-kb upstream region and a downstream hepatic enhancer region was integrated into the genome of the transgenic mice in the right order (Fig. 4C). -- 27895109 chr9 78368337 78376479 SHH In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes. human epithelial Low+High throughput Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes 否 -- embryonic stem cell E_02_0820 Luciferase Reporter Assay,RT-qPCR,ChIP-seq Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B). Deletion of the entire EC(DppUp) significantly affects the expression of both Dppa5a and Ooep, although the effect on Ooep is much greater (92% reduction compared to a 36% reduction).Enhancer activity was identified in a reporter assay for the ?1 enhancer and the ?5.8 enhancer within the EC(DppUpA) and EC(DppUpB) regions, respectively. Enhancer -- Luciferase Reporter Assay,RT-qPCR,ChIP-seq AA536857,Dppa5,Esg1,ecat2,2410146L05Rik,Floped,Moep19,Sddr Robust transcriptional output can be achieved by an isolated enhancer,clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes. ChIP-seq This occurs despite the fact that deletion of EC(DppDn) alone has only a modest effect on both Dppa5a (16% reduction) and Ooep (15% reduction) ex_x0002_pression (Table 1). This finding indicates partially redundant control of Dppa5a and Ooep by Enhancers in the upstream and downstream EC. -- -- -- -- Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep,Dppa5a,Ooep --,--,--,--,--,--,--,--,--,--,--,--,--,--,-- We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B).;We found that the enhancer cluster EC(DppUp), which lies between the Dppa5a and Ooep genes, regulated both Dppa5a and Ooep in cis. We considered two alternatives for the mechanism underlying this observation: Either this region contained two distinct regulatory modules, one for Dppa5a and one for Ooep, or each of the enhancers within the cluster contributed to the expression of both genes. To differentiate between these two alternatives, we split the EC into two segments and deleted each individually (Fig. 2). The region closest to Ooep, EC(DppUpB), contains one MTL bound by four transcription factors, whereas the region closest to Dppa5a, EC(DppUpA), contains three separate MTLs. Reporter assays revealed that each of these regions contained an active enhancer (Fig. 2B). --;--;--;--;--;--;--;--;--;--;--;--;--;--;-- 27881681 chr7 129554284 129564284 SOX9 Here, we aimed to determine the role of the novel SOX9-binding site in intron 6. We prepared reporter constructs that contain a Col2a1 promoter, intron 1 with or without intron 6, and the luciferase gene. Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5-10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. Furthermore, SOX9, but not SOX5, binds to this region as demonstrated in an electrophoretic mobility shift assay, although both SOX9 and SOX5 bind to a larger 325-bp fragment of intron 6 containing this small sequence. These findings suggest a novel mechanism of action of SOX5/6; namely, the SOX9/5/6 combination enhances Col2a1 transcription through a novel enhancer in intron 6 together with the enhancer in intron 1. human epithelial Low+High throughput A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent Enhancer in Intron 6 否 Skeletal Diseases Chondrosarcoma Cell E_02_0821 Luciferase Reporter Assay,ChIP-seq However, ChIP sequencing revealed that SOX9 does not strongly bind to intron 1, but rather it binds to intron 6 and a site 30 kb upstream of the transcription start site. Here, we aimed to determine the role of the novel SOX9-binding site in intron 6. We prepared reporter constructs that contain a Col2a1 promoter, intron 1 with or without intron 6, and the luciferase gene. Enhancer CRISPR/Cas9 Luciferase Reporter Assay,ChIP-seq Col2,Col2a,Col2a-1,Del1,Dmm,Lpk,M100413,Rgsc413,Rgsc856 -- -- -- 2010306G03Rik,AV220920,mKIAA4243 ChIP-seq,ChIP-qPCR,EMSA -- -- Col2a1,Col2a1,Col2a1,Col2a1 Sox9,Sox9,Sox9,Sox9 the ChIP-Seq data of SOX9 in the Col2a1 gene using rat chondrosarcoma cells (RCS cells)show that there is a strong SOX9-binding site in intron 6 and a weaker binding site in intron 1.Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5–10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. ;the ChIP-Seq data of SOX9 in the Col2a1 gene using rat chondrosarcoma cells (RCS cells)show that there is a strong SOX9-binding site in intron 6 and a weaker binding site in intron 1.Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5–10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. ;the ChIP-Seq data of SOX9 in the Col2a1 gene using rat chondrosarcoma cells (RCS cells)show that there is a strong SOX9-binding site in intron 6 and a weaker binding site in intron 1.Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5–10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. ;the ChIP-Seq data of SOX9 in the Col2a1 gene using rat chondrosarcoma cells (RCS cells)show that there is a strong SOX9-binding site in intron 6 and a weaker binding site in intron 1.Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5–10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. SOX9 bind to intron 6 and the binding of SOX5/SOX6 to intron 6 may facilitate the binding of SOX9 to the intron 1.To explore this possibility, we tested whether SOX9 and SOX5 bound to the SB2 fragment(600bp)shownabove or an even shorter fragment by means of an EMSA.;SOX9 bind to intron 6 and the binding of SOX5/SOX6 to intron 6 may facilitate the binding of SOX9 to the intron 1.To explore this possibility, we tested whether SOX9 and SOX5 bound to the SB2 fragment(600bp)shownabove or an even shorter fragment by means of an EMSA.;SOX9 bind to intron 6 and the binding of SOX5/SOX6 to intron 6 may facilitate the binding of SOX9 to the intron 1.To explore this possibility, we tested whether SOX9 and SOX5 bound to the SB2 fragment(600bp)shownabove or an even shorter fragment by means of an EMSA.;SOX9 bind to intron 6 and the binding of SOX5/SOX6 to intron 6 may facilitate the binding of SOX9 to the intron 1.To explore this possibility, we tested whether SOX9 and SOX5 bound to the SB2 fragment(600bp)shownabove or an even shorter fragment by means of an EMSA. 27869826 chr11 2219531 2239062 IRS4 We demonstrate that IRS4 overexpression in lung cancer is associated with recurrent deletions in cis, and we present evidence supporting a tumor-promoting role. human lung Low+High throughput Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking 否 Lung Cancer HCC-15 cell E_02_0822 ChIP-seq,Luciferase Reporter Assay We next performed ChIP-Seq at the IGF2 locus, detecting an accumulation of the active chromatin mark H3K27ac at a previously identified IGF2 enhancer66 herein referred to as IGF2 cognate enhancer (Fig. 5a, Supplementary Fig. 11). An even more pronounced H3K27ac peak, however, intersected with an element previously inferred to represent a lineage-specific super-enhancer in CRC cell lines (VACO-400 and VACO-9M)46.To verify enhancer function, we performed luciferase assays revealing enhancer activity of cloned fragments of this previously inferred super-enhancer46 in the HCT116 colon cancer but not in a control (HeLa) cancer cell line (Supplementary Fig. 12 and Supplementary Table 6). Super-Enhancer -- Luciferase Reporter Assay C11orf43,GRDF,IGF-II,PP9974 this IGF2 region indeed interacts with and hence represents a candidate IGF2 Enhancer. 4C-seq we additionally performed 4C-Seq (chromosome conformation capture sequencing63) experiments employing the putative CRE downstream of IRS4 as a viewpoint -- -- -- -- IGF2 -- To verify enhancer function, we performed luciferase assays revealing enhancer activity of cloned fragments of this previously inferred super-enhancer46 in the HCT116 colon cancer but not in a control (HeLa) cancer cell line (Supplementary Fig. 12 and Supplementary Table 6). -- 27333824 chr1 183149939 183150336 CDX2 Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation. human Intestinal epithelium Low throughput Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation 否 -- enterocyte E_02_0823 Luciferase Reporter Assay To determine whether CDX2 regulates the basal LAMC2 gene activity, a luciferase reporter gene driven by the LAMC2 promoter with and without the upstream LAMC2 enhancer identi?ed previously [Boyd et al., 2014] was transfected into Caco-2 cells without or with concomitant CDX2 expression plasmid. Over-expression of CDX2 increased the luciferase activity driven by the enhancer-less construct of LAMC2 by 2.5-fold (P?0.028) relative to cells transfected with the LAMC2 reporter vector alone, whereas the LAMC2 promoter with enhancer construct gave a fourfold increase (P?0.006) in reporter signal when co-transfected with CDX2 expression plasmid relative to cells transfected with the LAMC2 promoter/enhancer reporter vector alone (Fig. 1A). The LAMC2 luciferase reporter constructs were: pGL3-LAMC2 containing the 1.2 kb human LAMC2 promoter region upstream of transcription start site [Olsen et al., 2000], and pGL3-LAMC2+ Enhancer containing the 1.2 kb LAMC2 promoter and the enhancer region at chr1:183,149,939–183,150,336 (hg19) [Boyd et al., 2014]. Enhancer -- Luciferase Reporter Assay B2T,BM600,CSF,EBR2,EBR2A,LAMB2T,LAMNB2 -- -- -- CDX-3/AS, CDX3, CDX2 ChIP-seq -- -- LAMC2 CDX2 To determine whether CDX2 regulates the basal LAMC2 gene activity, a luciferase reporter gene driven by the LAMC2 promoter with and without the upstream LAMC2 enhancer identi?ed previously [Boyd et al., 2014] was transfected into Caco-2 cells without or with concomitant CDX2 expression plasmid. Over-expression of CDX2 increased the luciferase activity driven by the enhancer-less construct of LAMC2 by 2.5-fold (P?0.028) relative to cells transfected with the LAMC2 reporter vector alone, whereas the LAMC2 promoter with enhancer construct gave a fourfold increase (P?0.006) in reporter signal when co-transfected with CDX2 expression plasmid relative to cells transfected with the LAMC2 promoter/enhancer reporter vector alone (Fig. 1A). Thus, to further analyze,whether LAMC2 is a direct target of CDX2 also in the native chromatin environment, we performed ChIP experiments with Caco-2 and with cells purified from human colonic tissue samples. 27207652 chr11 95817801 95818824 DNMT3B This condensed chromatin structure is associated with binding of DNMT3B and decreased occupancy of OCT1 transcription factor at MAML2 enhancer, suggesting a role of DNMT3B in increasing methylation of MAML2 after stilbenoid treatment. Our results deliver a novel insight into epigenetic regulation of oncogenic signals in cancer and provide support for epigenetic-targeting strategies as an effective anticancer approac human connective Low+High throughput Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity 否 Breast Cancer MCF10CA1h,MCF10CA1a cell E_02_0824 ChIP,qPCR,Transfection,Western blot The difference in DNA meth_x0002_ylation within MAML2 in RSV treated versus control cells was determined as 0.37 in MCF10CA1h and 0.1 in MCF10CA1a cells based on the array data. These elevated levels of methylation were identified in a fragment corresponding to the predic_x0002_tive enhancer within MAML2 gene body. It has been demonstrated that active enhancers are enriched with H3K27ac.We confirmed by ChIP assay that this histone mark is present at MAML2 in cancer cells and its occupancy is significantly reduced by RSV.These data strongly support the role of this region as a gene enhancer and the role of RSV in decreasing the activ_x0002_ity of this enhancer. Enhancer -- ChIP,Transfection,Western blot MAM-3,MAM2,MAM3,MLL-MAML2 -- -- -- OCT1,OTF1,oct-1B ChIP,qPCR -- -- MAML2 POU2F1 MAML2, a coactivator of NOTCH targets, is methylated at the enhancer region and transcriptionally silenced in response to stilbenoids, possibly explaining the downregulation of NOTCH target genes.It has been demonstrated that active enhancers are enriched with H3K27ac.We confirmed by ChIP assay that this histone mark is present at MAML2 in cancer cells and its occupancy is significantly reduced by RSV. Using ChIP, we confirmed OCT1 binding to MAML2 enhancer (Figure?6C, control cells). The binding dramati_x0002_cally decreases upon treatment of MCF10CA1a with 15?μM RSV.The lack of OCT1 binding may be directly linked to MAML2 transcriptional silencing. To test this hypothesis, we depleted OCT1 in MCF10CA1a cells using SmartPool siRNA mixture and four siRNA sequences separately, as confirmed by QPCR and western blot and tested the effect of OCT1 absence on MAML2 expression. 27166834 chr8 120876144 120876856 CTCF We describe enhancer-blocking or boundary elements on either side of the locus that are bound in vivo by the transcription factor CTCF, but we found that they do not coincide with transitions in nuclease sensitivity flanking the locus or with patterns of histone modifications within it. human Low+High throughput A Complex Chromatin Landscape Revealed by Patterns of Nuclease Sensitivity and Histone Modification within the Mouse 尾-Globin Locus 否 -- embryonic cell E_02_0825 3C,ChIP-seq To identify the presence of physical interaction between the 11 enhancer candidates and the Foxf1 promoter, 3C assays were performed. Among 11 selected regions, three enhancer candidates demonstrated interactions with the Foxf1 promoter. Enhancer 3C RT-qPCR,DNaseI-seq,Transgenic mice AI450827,FREAC1a,Freac-1,HFH-8,Hfh8,Foxf1 -- -- -- AV235269,Zfp-5,Zfp5;Gli2,AI854843,AU023367,Bph,GLI3-190,GLI3FL,Pdn,Xt,add RT-qPCR,Luciferase Reporter Assay -- -- Foxf1 Gli1,Gli2,Gli3 To investigate the in vivo activity of the discovered enhanc_x0002_ers and compare the location of activity with Foxf1-express_x0002_ing regions, we generated enhancer-driven lacZ-reporter mice 5′e207mFoxf1-lacZ and 5′e201mFoxf1-lacZ.Foxf1 mRNA was expressed in the maxilla, mandible, limbs, sclerotome and gut of wild-type mouse embryos at E12 (Fig. 2a), whereas lacZ-positive cells were observed in part of the forebrain and neural tube in 5′e207mFoxf1-lacZ transgenic mice at E11 and E12 as well as 5′e201mFoxf1-lacZ transgenic mouse embryos at E11 after x-gal staining.Foxf1 was also expressed in the mesenchyme surrounding epithelial buds in lungs at E12. Schematic drawing of luciferase reporter constructs containing 112 bp 5′e207mFoxf1 and 173 bp 5′e201mFoxf1 fragments with Gli binding sites is shown. Luciferase reporter constructs were assayed for luciferase activity without or with Gli1 over-expression vector at 50 or 100 ng. 27149122 chr5 110175800 110176600 TSLP Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. human heart low throughput Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure 是 rs9885413 Heart Failure 293T cell E_02_0826 Luciferase Reporter Assay To experimentally test the effect of rs9885413 on enhancer activity, the 100 bp region flanking the SNP (50 bp on either side) was cloned into a reporter vector and transfected into HEK293 cells expressing NHLH1 (S1 Text). Luciferase activity measured after 24 hours was 4-fold higher with a construct corresponding to the risk allele as compared to the wild-type allele (S4 Fig, P < 0.001), indicating that the risk allele of rs9885413 substantially increases enhancer activity. enhancer -- Luciferase Reporter Assay TSLP -- -- -- -- -- 110176128 Transfection,Luciferase Reporter Assay TSLP -- To experimentally test the effect of rs9885413 on enhancer activity, the 100 bp region flanking the SNP (50 bp on either side) was cloned into a reporter vector and transfected into HEK293 cells expressing NHLH1 (S1 Text). Luciferase activity measured after 24 hours was 4-fold higher with a construct corresponding to the risk allele as compared to the wild-type allele (S4 Fig, P < 0.001), indicating that the risk allele of rs9885413 substantially increases enhancer activity. -- 26937964 chr7 35156353 35161233 Runx1 CRISPR/Cas9-mediated replacement of the wild-type enhancer with a variant mutant in its seven Ets sites leads to 20-fold reduction of Cebpa mRNA in the 32Dcl3 myeloid cell line. To determine the effect of deleting the enhancer in vivo, we now characterize C57BL/6 mice in which loxP sites flank a 688 bp DNA segment containing the enhancer. CMV-Cre mediated germline deletion resulted in diminution of the expected number of viable Enh(f/f);CMV-Cre offspring, with 28-fold reduction in marrow Cebpa mRNA but normal levels in liver, lung, adipose, intestine, muscle, and kidney. Cre-transduction of lineage-negative marrow cells in vitro reduced Cebpa mRNA 12-fold, with impairment of granulocytic maturation, morphologic blast accumulation, and IL-3 dependent myeloid colony replating for >12 generations. Exposure of Enh(f/f);Mx1-Cre mice to pIpC led to 14-fold reduction of Cebpa mRNA in GMP or CMP, 30-fold reduction in LSK, and <2-fold reduction in the LSK/SLAM subset. FACS analysis of marrow from these mice revealed 10-fold reduced neutrophils, 3-fold decreased GMP, and 3-fold increased LSK cells. Progenitor cell cycle progression was mildly impaired. Granulocyte and B lymphoid colony forming units were reduced while monocytic and erythroid colonies were increased, with reduced Pu.1 and Gfi1 and increased Egr1 and Klf4 in GMP. Finally, competitive transplantation indicated preservation of functional long-term hematopoietic stem cells upon enhancer deletion and confirmed marrow-intrinsic impairment of granulopoiesis and B cell generation with LSK and monocyte lineage expansion. These findings demonstrate a critical role for the +37 kb Cebpa enhancer for hematopoietic-specific Cebpa expression, with enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion. mouse connective Low+High throughput In Vivo Deletion of the Cebpa +37 kb Enhancer Markedly Reduces Cebpa mRNA in Myeloid Progenitors but Not in Non-Hematopoietic Tissues to Impair Granulopoiesis 否 -- bone marrow cell E_02_0827 ChIP-seq,CRISPR/Cas9,Transgenic mice To determine the effect of deleting the enhancer in vivo, we now characterize C57BL/6 mice in which loxP sites flank a 688 bp DNA segment containing the enhancer. Enhancer CRISPR/Cas9 ChIP-seq C/ebpalpha,CBF-A,Cebp These findings demonstrate a critical role for the +37 kb Cebpa enhancer for hematopoietic-specific Cebpa expression, with enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion. CRISPR/Cas9,PCR,Western blot Together, these data indicate that reduced Cebpa expression consequent to +37 kb Enhancer deletion impairs hematopoietic cell autonomous granulopoiesis in vitro, leading to preservation of immature myeloid progenitors capable of long-term, IL-3-dependent proliferation without complete terminal maturation,a preleukemic phenotype. AML1,CBF-alpha-2,Cbfa2,Pebp2a2,Pebpa2b ChIP-seq -- -- Cebpa,Cebpa,Cebpa,Cebpa,Cebpa Runx1,Runx1,Runx1,Runx1,Runx1 These findings demonstrate a critical role for the +37 kb Cebpa Enhancer for hematopoietic-specific Cebpa expression,with Enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion.;These findings demonstrate a critical role for the +37 kb Cebpa Enhancer for hematopoietic-specific Cebpa expression,with Enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion.;These findings demonstrate a critical role for the +37 kb Cebpa Enhancer for hematopoietic-specific Cebpa expression,with Enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion.;These findings demonstrate a critical role for the +37 kb Cebpa Enhancer for hematopoietic-specific Cebpa expression,with Enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion.;These findings demonstrate a critical role for the +37 kb Cebpa Enhancer for hematopoietic-specific Cebpa expression,with Enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion. Runx1,C/EBPα,Spi1,Erg,Fli-1,GATA2,Scl,Meis1,and Gfi-1b bind chromatin in the region of this Enhancer in hematopoietic cells as determined by ChIP-Seq.;Runx1,C/EBPα,Spi1,Erg,Fli-1,GATA2,Scl,Meis1,and Gfi-1b bind chromatin in the region of this Enhancer in hematopoietic cells as determined by ChIP-Seq.;Runx1,C/EBPα,Spi1,Erg,Fli-1,GATA2,Scl,Meis1,and Gfi-1b bind chromatin in the region of this Enhancer in hematopoietic cells as determined by ChIP-Seq.;Runx1,C/EBPα,Spi1,Erg,Fli-1,GATA2,Scl,Meis1,and Gfi-1b bind chromatin in the region of this Enhancer in hematopoietic cells as determined by ChIP-Seq.;Runx1,C/EBPα,Spi1,Erg,Fli-1,GATA2,Scl,Meis1,and Gfi-1b bind chromatin in the region of this Enhancer in hematopoietic cells as determined by ChIP-Seq. 26916345 chr1 67739940 67741075 IL12RB2 The proportion of IFN-γ+ CD4+ T-cells was increased in 'A/A' homozygotes (p=0.004), but neither IL23R nor IL12RB2 mRNA was affected. human bone low throughput An ankylosing spondylitis-associated genetic variant in the IL23R-IL12RB2 intergenic region modulates enhancer activity and is associated with increased Th1-cell differentiation 是 rs11209026 Ankylosing Spondylitis Lymphoblastoid cell lines E_02_0828 DNase I Hypersensitivity Assay We identified a PRE (Chr1:67739940–67741075) located 14.2 kb downstream of IL23R and 33.1 kb upstream of IL12RB2.This region is DNase I hypersensitive (in Th1-cells, but not Th17-cells) and exhibits TF binding (lymphoblastoid cell line; GM12878) and enhancer-associated H3K4me1 methylation (CD4+ CD25? IL-17A? T-cells; PMA and ionomycin-stimulated). enhancer -- DNase I Hypersensitivity Assay IL23R -- -- -- -- -- 67705958 DNase I Hypersensitivity Assay,Luciferase Reporter Assay IL23R -- We identified a PRE (Chr1:67739940–67741075) located 14.2 kb downstream of IL23R and 33.1 kb upstream of IL12RB2.This region is DNase I hypersensitive (in Th1-cells, but not Th17-cells) and exhibits TF binding (lymphoblastoid cell line; GM12878) and enhancer-associated H3K4me1 methylation (CD4+ CD25? IL-17A? T-cells; PMA and ionomycin-stimulated). -- 26886256 chr6 43891400 43898360 VEGFA Further analyses of a hypomethylated ESSE downstream to the VEGFA gene revealed a novel regulatory circuit affecting VEGFA transcript levels across cancers and patients. human lymph Low+High throughput Embryonic Stem Cell (ES)-Specific Enhancers Specify the Expression Potential of ES Genes in Cancer -- K-562 CELL E_02_0829 ChIP-seq We termed these promoter-distal elements, which carry the H3K4me1 mark in ES but not in hematopoietic cells,the ES-specific enhancers (ESSEs) of the hematopoietic cell lineage. enhancer 4C-seq,CRISPR/Cas9 Luciferase Reporter Assay MVCD1, VEGF, VPF -- -- -- CANDF7,IMD31A,IMD31B,IMD31C,ISGF-3,STAT91,IMD44,ISGF-3,P113,STAT113 ChIP-seq -- -- VEGFA STAT1/2 To determine whether this ESSE is able to enhance transcription, a 1,500 bp fragment surrounding the ESSE methylation site was cloned upstream to a minimal SV40 promoter in a luciferase reporter plasmid and transfected to K562 cells.Indeed, the ESSE segment significantly enhanced expression when placed upstream or downstream to the minimal promoter. Thus,the DNA element surrounding the ESSE site is a transcriptional enhancer in leukemia cells.The Circularized Chromosome Conformation Capture (4C-seqencing) assay allowed mapping the interactions between the VEGFA promoter and DNA sequences across the K562 cell genome.To determine whether VEGFA expression depends upon the ESSE, we mutated the ESSE site in K562 cells by utilization of the CRISPR/Cas9 genome-editing system. Focused (<600 bp) cluster of transcription factor binding sites (Chip-seq data) within the predicted enhancer. The factors bound in K562 cells are listed. This is the only cluster within 20 kb around the ESSE. 26884396 chr14 61121917 61123917 Six2 We compared the regulatory actions of Six2 in mouse and human nephron progenitors by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). mouse Low+High throughput Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators 否 -- nephron progenitor cell E_02_0830 ChIP-seq ChIP-seq was performed on 17 week fetal kidneys and E16.5 mouse kidneys to assess chromatin marks associated with active genes and enhancers (H3K27ac) and transcriptionally silenced chromatin (H3K27me3). Similarly, the human SIX1 locus was bound by SIX2 at multiple conserved elements and displayed prominent H3K27ac throughout the gene body and the SIX2-bound regions (Fig. 3A). Enhancer -- RNA-seq BOS3,DFNA23,TIP39 -- -- -- SIX2 ChIP -- -- SIX1,SIX1 SIX2,SIX2 Using RNA-seq data from nephron progenitors, we compared expression of genes between human and mouse and identified genes that were >5-fold enriched in either species and were also a species-specific target (Fig. 2E, right panel,highlighted genes). SIX1 is expressed in the human ITGA8+progenitors, but not in mouse nephron progenitors, identifying SIX1 as a human specific target on the basis of both cis-interactions around the SIX1 gene and active SIX1 expression (right panelFig. 2E; Table S3).;Using RNA-seq data from nephron progenitors, we compared expression of genes between human and mouse and identified genes that were >5-fold enriched in either species and were also a species-specific target (Fig. 2E, right panel,highlighted genes). SIX1 is expressed in the human ITGA8+progenitors, but not in mouse nephron progenitors, identifying SIX1 as a human specific target on the basis of both cis-interactions around the SIX1 gene and active SIX1 expression (right panelFig. 2E; Table S3). The differing number of peaks was due to lower levels of SIX2 ChIP enrichment in the second replicate (Fig. S1C). Examination of SIX2 binding near MEOX1 and WT1 highlighted the similar binding profiles for SIX2 replicates(Fig. 1B).;The differing number of peaks was due to lower levels of SIX2 ChIP enrichment in the second replicate (Fig. S1C). Examination of SIX2 binding near MEOX1 and WT1 highlighted the similar binding profiles for SIX2 replicates(Fig. 1B). 26864944 chr14 24435744 24437744 DHRS4 The human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene-duplication events. human Cancer Low throughput Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster 否 -- Hep G2,HL-7702 cell E_02_0831 Luciferase Reporter Assay,ChIP we searched for and identified a putative enhancer region located 13.8 kb downstream from the TSS of DHRS4-AS117,18. We performed chromatin immunoprecipitation (ChIP) to confirm the enrichment of histone modifications in hepatocellular carcinoma cells (HepG2) and normal hepatocytes (HL7702) (Fig.?1D). We then examined the potential enhancement of luciferase reporter activity by using luciferase reporter assays in HepG2 and HL7702 cells (Fig.?1E). Enhancer 3C Luciferase Reporter Assay,ChIP,qPCR AS1DHRS4,C14orf167,C14orf67,DHRS4AS1,PRO1488 -- -- -- KAT3B,MKHK2,RSTS2,p300 ChIP -- -- DHRS4-AS1 EP300 In a search of the DHRS4-AS1 region for nearby enhancers, we identified an enhancer located 13.8 kb downstream of the DHRS4-AS1 transcriptional start site. We further showed, by using a chromosome conformation capture (3C) assay, that this enhancer is capable of physically interacting with the DHRS4-AS1 promoter through chromosomal looping. RNA pol II and the transcriptional coactivator p300/CBP occupy enhancer regions and target gene promoters to maintain chromatin loops29. We next characterized the effect of AS1eRNA knockdown on the binding levels of RNA pol II and p300 at the AS1 enhancer and the DHRS4-AS1 promoter (Fig.?4A,B). 26829750 chr9 14538685 14540685 TP63 MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. human lymph Low+High throughput An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma Adenoid Cystic Carcinoma MCF-7 cell E_02_0832 Luciferase Reporter Assay,RT-PCR,ChIP,ChIP-seq Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps highlight distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Enhancer 3C ChIP,ChIP-seq CTF,HMGIC/NFIB,MACID,NF-I/B,NF1-B,NFI-B,NFI-RED2,NFIB3,NFIB Here we identify the juxtaposition of super-enhancer regions to the MYB locus as the unifying feature of ACC translocations.Detailed genomic and epigenomic analyses of ACCs identify alternate rearrangements that translocate super-enhancers in the NFIB and 3C To test whether specific enhancers within the translocated super_x0002_enhancers might activate the MYB promoter, we examined their physical proximity to the promoter using chromosome conforma_x0002_tion capture (3C).These data suggest that the translocations reposition super-enhancers that subsequently loop to the MYB promoter and sustain high-level MYB expression. AIS, B(p51A), B(p51B), EEC3, KET, LMS, NBP, OFC8, RHS, SHFM4, TP53CP, TP53L, TP73L, p40, p51, p53CP, p63, p73H, p73L ChIP-seq -- -- NFIB TP63 To test whether specific enhancers within the translocated super_x0002_enhancers might activate the MYB promoter, we examined their physical proximity to the promoter using chromosome conforma_x0002_tion capture (3C). First, we examined an ACC with a translocation involving MYB and the NFIB locus. To directly test whether TP63 co-binds with MYB, we mapped binding of this transcription factor by ChIP-seq.Remarkably, we found that 81% of TP63-binding sites in ACC were co-bound by MYB.These data suggest that MYB,TP63 and Notch signaling may coordinately orchestrate the diverse expression programs in ACC. 26813977 chr6 30904342 30904788 POU5F2 Unexpectedly, we also discovered a new class of enhancers that contribute to POU5F1 transcription in an unusual way: Disruption of such sequences led to a temporary loss of POU5F2 transcription that is fully restored after a few rounds of cell division. human Early embryos Low throughput A new class of temporarily phenotypic enhancers identified by CRISPR/Cas11-mediated genetic screening 否 -- embryonic stem cell E_02_0833 CRISPR/Cas9,Luciferase Reporter Assay,4C-seq We designed 1964 sgRNA sequences (Supplemental Table S2) targeting these putative cis-regulatory elements with an average of 11 sgRNA per element (Supplemental Fig. S1A). To eliminate these false positives,we required that a positive cis-regulatory element should have at least two distinct sgRNAs enriched by twofold or more in the eGFP? population in at least three out of the four independent experiments (Supplemental Table S3; Supplemental Fig. S2A). By use of this criterion, no negative control sgRNA passed the filter, while six cis-regulatory elements were identified as positives (Fig. 2A). Next, we tested whether the identified elements could function as enhancers in the classical reporter assays (DHS_37,CTCF_38, DHS_65, DHS_108, and DHS_115).We cloned genomic fragments corresponding to each element into a reporter plasmid containing the 360-bp POU5F1 core promoter region and a luciferase reporter gene. All elements, with the exception of DHS_65, exhibited significant enhancer activities in the H1 cells compared with the control plasmid containing only the POU5F1 core promoter sequence (Fig. 2C). We found that all Temp Enhancers, namely, DHS_37, DHS_65, and DHS_108, are located near regions that show high levels of chromatin interactions with the POU5F1 promoter. To confirm this observation, we also performed 4C-seq experiments in H1 POU5F1-eGFP cells. Again, we found these elements near regions displaying high and consistent interaction frequencies with the POU5F1 promoter (Fig. 4D). Enhancer 4C-seq Luciferase Reporter Assay OCT3, OCT4, OTF-3, OTF3, OTF4, Oct-3, Oct-4 DHS_65 and DHS_108 act in cis to regulate POU5F1 expression CRISPR/Cas9 Those results support our model that DHS_65 and DHS_108 act in cis to regulate POU5F1 transcription. -- -- -- -- POU5F1,POU5F1 --,-- Next, we tested whether the identified elements could function as enhancers in the classical reporter assays (DHS_37,CTCF_38, DHS_65, DHS_108, and DHS_115).We cloned genomic fragments corresponding to each element into a reporter plasmid containing the 360-bp POU5F1 core promoter region and a luciferase reporter gene. All elements, with the exception of DHS_65, exhibited significant enhancer activities in the H1 cells compared with the control plasmid containing only the POU5F1 core promoter sequence (Fig. 2C). We found that all Temp Enhancers, namely, DHS_37, DHS_65, and DHS_108, are located near regions that show high levels of chromatin interactions with the POU5F1 promoter. To confirm this observation, we also performed 4C-seq experiments in H1 POU5F1-eGFP cells. Again, we found these elements near regions displaying high and consistent interaction frequencies with the POU5F1 promoter (Fig. 4D).;Next, we tested whether the identified elements could function as enhancers in the classical reporter assays (DHS_37,CTCF_38, DHS_65, DHS_108, and DHS_115).We cloned genomic fragments corresponding to each element into a reporter plasmid containing the 360-bp POU5F1 core promoter region and a luciferase reporter gene. All elements, with the exception of DHS_65, exhibited significant enhancer activities in the H1 cells compared with the control plasmid containing only the POU5F1 core promoter sequence (Fig. 2C). We found that all Temp Enhancers, namely, DHS_37, DHS_65, and DHS_108, are located near regions that show high levels of chromatin interactions with the POU5F1 promoter. To confirm this observation, we also performed 4C-seq experiments in H1 POU5F1-eGFP cells. Again, we found these elements near regions displaying high and consistent interaction frequencies with the POU5F1 promoter (Fig. 4D). --;-- 26808502 chr2 10136078 10138078 Gata3 Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell-regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell-specific transcriptional activity. mouse connective Low throughput Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs 否 -- T cell E_02_0834 CRISPR/Cas9,ChIP,RT-PCR We next asked whether this 1.2-kb Gata3 Tce1 fragment was also necessary for the transcription of a reporter gene in T cells. To answer this question, we prepared another EGFP reporter plasmid in which the 1.2-kb sequence was deleted from full-length Tce1 (Figure 5A) and generated additional F0 Tg mice (TgΔ1.2 mice). None of the F0 TgΔ1.2 mice expressed EGFP in peripheral CD4 T cells (Table 1 and Supplemental Figure 5C) or in thymocytes (Figure 5, B and C), except possibly at the DN4 stage (Table 2). We also analyzed TgΔ1.7, TgΔ1.5, and TgΔ2.7 mice and found that all of them expressed EGFP in peripheral CD4 T cells (Tables 1 and ?and2).2). Therefore, the EGFP expression in those mice confirmed that these sequences were not required for Tce1 enhancer activity in peripheral CD4 T cells. These data show that the 1.2-kb T cell enhancer fragment within Tce1 is also necessary for reporter gene transcription in T cells and, taken together with the data shown in Figure 1, that this fragment functions as an enhancer core element in vivo for Gata3 T cell–specific transcription. Enhancer CRISPR/Cas9 ChIP,PCR Gata-3,jal Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell–specific transcriptional activity. CRISPR/Cas9,ChIP,RT-PCR Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte–specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell–regulatory element. AI465550,TCF-1,Tcf1,A130037E08Rik,ALF1,HEB,HEBAlt,HTF-4,HTF4,ME1,REB,bHLHb20,AI843960,CBF1,Igkjrb,Igkrsbp,RBP-J,RBP-Jkappa,RBP-Jkappa,RBPjk,Rbpsuh ChIP -- -- Gata3 Tcf7,Tcf12,Rbpj As anticipated, homozygous loss of Tce1 (Tce1–/–) led to a reduction in the number of ETPs (62% of that of heterozygous controls), and Gata3 mRNA in the remaining ETPs was only 52% of that of controls (Figure 1B). In contrast, the number of Tce1–/– DN2 and DN3 stage cells was unaltered compared with that of controls, although Gata3 mRNA levels in DN2 thymocytes were reduced (83% of that of heterozygous controls; Figure 1B). We therefore examined the association of CSL/RBP-J with predicted binding sites within Tce1. CSL/RBP-J binding to the Cd25 locus, a robust direct Notch target gene, was used as a positive control with an anti–RBP-J antibody in ChIP assays.Taken together, these data show that at least 3 critical T cell–affiliated transcription factors, TCF-1, HEB, and CSL/RBP-J, occupy binding sites within Tce1 at different developmental stages.Since all 3 have been shown to vitally affect T cell development, it seems likely that these factors and their associated signaling pathways directly modulate Gata3 expression through their binding to multiple consensus sites within Tce1. 26795348 chr2 202120390 202125986 CASP8 we implicate three regulatory variants at 2q33 that target CASP8 (rs3769823,rs3769821 in CASP8, and rs10197246 in ALS2CR12) as func- tionally relevant. We conclude that nested discordant haplo- type sequencing is a promising approach to aid mapping of low-risk association loci. human connective Low+High throughput Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus. 否 Breast Cancer Chronic lymphocytic leukemia cell E_02_0835 PCR,Luciferase Reporter Assay,ChIP-seq Variants rs3769823, rs3769821, and rs10197246 were chosen to investigate for ability to affect enhancer activity. To create the enhancer constructs, we performed PCR using genomic DNA from T-47D, which is homozygous for risk alleles at all three SNPs, and MCF10A, which is homozygous for neutral alleles, using the following primer pairs. Enhancer -- DNase I Hypersensitivity Assay CASP-8, FLICE, MACH, Mch5 -- -- -- 1110034C02Rik, AW109958, Aprf,MRTLC,bHLHe39,c-Myc,MYC,MRD21 DNase I Hypersensitivity Assay,ChIP-seq -- -- CASP8 STAT3,MYC,CTCF To prioritize further, we used expression-quantitative trait locus analysis of RNA sequencing from breast tissues, gene regulation annota_x0002_tions from the ENCODE consortium, and functional assays for differential enhancer activities. Notably, we implicate three regulatory variants at 2q33 that target CASP8 (rs3769823, rs3769821 in CASP8, and rs10197246 in ALS2CR12) as func_x0002_tionally relevant. The first two reside 435 bp apart in a promoter proximal region that exhibits DNAse I hypersensitivity in mammary epithelial and breast cancer cell lines, and binds multiple transcription factors(STAT3, MYC, Pol2, and CTCF) based on ENCODE data (22).Also notable are results from an eQTL study in blood (23),indicating highly significant decreased CASP8 expression associ_x0002_ated with these cFSVs and suggesting the expression signature is also readily observed in blood. 26766440 chr8 23448386 23454886 GATA2 Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progenitor cells and committed erythroid progenitors. We find that enhancers are modulated pervasively and direct lineage- and stage-specific transcription. GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning. Examination of lineage-specific enhancers identifies transcription factors and their combinatorial patterns in enhancer turnover. Importantly, by CRISPR/Cas9-mediated genomic editing, we uncover functional hierarchy of constituent enhancers within the SLC25A37 super-enhancer. Despite indistinguishable chromatin features, we reveal through genomic editing the functional diversity of several GATA switch enhancers in which enhancers with opposing functions cooperate to coordinate transcription. Thus, genome-wide enhancer profiling coupled with in situ enhancer editing provide critical insights into the functional complexity of enhancers during development. human epithelial Low+High throughput Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis 否 -- Erythroid lineage cell E_02_0836 CRISPR/Cas9,ChIP-seq The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). We designed sequence-specific guide RNAs (or sgRNAs) flanking each constituent enhancer (E1, E2 and E3) or the promoter (P) (Figure 3B). Upon transfection into undifferentiated G1E cells together with an SpCas9 expressing construct, we screened and obtained multiple independent single cell-derived clones containing bi-allelic deletion of each enhancer (Figure S2B,C). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C). Enhancer CRISPR/Cas9 ChIP-seq HT015,MFRN,MFRN1,MSC,MSCP,PRO1278,PRO1584,PRO2217 GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning. CRISPR/Cas9 While the E2 and E3 Enhancers are indispensable for maximal Gata2 activation in stem/progenitor cells, the E1 Enhancer is required to maintain Gata2 repression in committed erythroid cells. ERYF1,GATA-1,GF-1,GF1,NF-E1,NFE1,XLANP,XLTDA,XLTT,SCL,TCL5,bHLHa17,tal-1 ChIP-seq -- -- SLC25A37 ,SLC25A37 ,SLC25A37 ,SLC25A37 GATA1,TAL1,GATA1,TAL1,GATA1,TAL1,GATA1,TAL1 The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C). ;The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C). ;The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C). ;The enhancer cluster upstream of the SLC25A37 gene, consisting of three distinct constituent enhancers as measured by H3K4me1 and H3K27ac ChIP-seq, is defined as an erythroid-specific super-enhancer in both human (A5 ProE) and mouse (G1ER) erythroid cells (Figure 3A; Table S4). To define the regulatory components of the SLC25A37 super-enhancer, we asked whether the function of each constituent enhancer depends on the activity of neighboring enhancers in situ. We employed site-directed loss-of-function analysis of the SLC25A37 super-enhancer constituents using CRISPR/Cas9-mediated genomic engineering.We focused on the orthologous mouse super-enhancer in the murine G1E/G1ER erythroid cell model (Welch et al., 2004). Surprisingly, knockout of individual enhancers confer markedly varying effects on Slc25a37 expression. Specifically, while deletion of E1 or E2 individually only modestly or slightly impairs Slc25a37 activation during differentiation, respectively, E3 deletion abolishes its activation resulting in a 15-fold decrease in expression (48h after β-estradiol treatment; Figure 3C). Strikingly, while only 3% (22,570 of 707,718) of the GATA1 motif-matched loci are covered by GATA1 ChIP-seq at a genome scale in ProEs, 34% of identified GATA1 motifs are covered by GATA1 within the Enhancer context.Similar pattern is observed for another principal erythroid regulator TAL1.;Strikingly, while only 3% (22,570 of 707,718) of the GATA1 motif-matched loci are covered by GATA1 ChIP-seq at a genome scale in ProEs, 34% of identified GATA1 motifs are covered by GATA1 within the Enhancer context.Similar pattern is observed for another principal erythroid regulator TAL1.;Strikingly, while only 3% (22,570 of 707,718) of the GATA1 motif-matched loci are covered by GATA1 ChIP-seq at a genome scale in ProEs, 34% of identified GATA1 motifs are covered by GATA1 within the Enhancer context.Similar pattern is observed for another principal erythroid regulator TAL1.;Strikingly, while only 3% (22,570 of 707,718) of the GATA1 motif-matched loci are covered by GATA1 ChIP-seq at a genome scale in ProEs, 34% of identified GATA1 motifs are covered by GATA1 within the Enhancer context.Similar pattern is observed for another principal erythroid regulator TAL1. 26748758 chr2 172513228 172520500 Foxd3 Using mouse embryonic stem cells as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for exit from naive pluripotency and progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naive pluripotency expression program through decommissioning of active enhancers associated with key naive pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow re-activation of relevant genes required for proper PGC specification. Our findings therefore uncover a cycle of activation and deactivation of Foxd3 required for exit from naive pluripotency and subsequent PGC specification. mouse epithelial Low+High throughput Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification 否 -- embryonic stem cell E_02_0837 ChIP-seq,RT-qPCR To test if Foxd3 was indeed able to silence na?ve pluripotency enhancers, we evaluated the impact of Foxd3 overexpression on some of these regulatory elements. tetOn Foxd3 mESC were treated with Dox and the levels of various histone modifications (i.e. H3K27ac, H3K27me2, H3K4me1, H3K4me2) at selected enhancers were evaluated by ChIP-qPCR. Compared to control cells, tetOn Foxd3 cells displayed lower levels of H3K27ac and H3K4me2 (active enhancers) , increased H3K27me2 (inactive enhancers) and minor changes in H3K4me1 levels (active and inactive enhancers)at most of the analysed na?ve enhancers (Figure 4B-C, Figure S5A-B). Enhancer -- ChIP-seq,RT-qPCR AA409384,AP2gamma,Ap-2.2,Stra2,Tcfap2c -- -- -- CWH3,Genesis,Hfh2 ChIP-qPCR -- -- Tfap2C,Tfap2C Foxd3,Foxd3 ChIP-Seq profiles generated in Foxd3-FH mES cells with anti-HA and anti-Flag antibodies around a representative locus (i.e.,Tfap2c).;ChIP-Seq profiles generated in Foxd3-FH mES cells with anti-HA and anti-Flag antibodies around a representative locus (i.e.,Tfap2c). To test if Foxd3 was indeed able to silence naive pluripotency enhancers, we evaluated the impact of Foxd3 overexpression on some of these regulatory elements. tetOn Foxd3 mESCs were treated with Dox, and the levels of various histone modifications (i.e., H3K27ac, H3K27me2, H3K4me1, and H3K4me2) at selected enhancers were evaluated by ChIP-qPCR. Compared to control cells, tetOn Foxd3 cells displayed lower levels of H3K27ac and H3K4me2 (active enhancers) , increased H3K27me2 (inactive enhancers) and minor changes in H3K4me1 levels (active and inactive enhancers)at most of the analysed na?ve enhancers (Figure 4B-C, Figure S5A-B).Using RT-qPCR, we found that Foxd3 overexpression significantly reduced eRNA levels at most of the analysed enhancers (Figure S5C). The role of Foxd3 was similarly evaluated using Foxd3?/? mESC, which displayed increased levels of H3K27ac and H3K4me2 (Figure 4D-E) and minor changes in H3K27me2 (Figure S5D) at most of the analysed enhancers.;To test if Foxd3 was indeed able to silence naive pluripotency enhancers, we evaluated the impact of Foxd3 overexpression on some of these regulatory elements. tetOn Foxd3 mESCs were treated with Dox, and the levels of various histone modifications (i.e., H3K27ac, H3K27me2, H3K4me1, and H3K4me2) at selected enhancers were evaluated by ChIP-qPCR. Compared to control cells, tetOn Foxd3 cells displayed lower levels of H3K27ac and H3K4me2 (active enhancers) , increased H3K27me2 (inactive enhancers) and minor changes in H3K4me1 levels (active and inactive enhancers)at most of the analysed na?ve enhancers (Figure 4B-C, Figure S5A-B).Using RT-qPCR, we found that Foxd3 overexpression significantly reduced eRNA levels at most of the analysed enhancers (Figure S5C). The role of Foxd3 was similarly evaluated using Foxd3?/? mESC, which displayed increased levels of H3K27ac and H3K4me2 (Figure 4D-E) and minor changes in H3K27me2 (Figure S5D) at most of the analysed enhancers. 26745862 chr6 36640937 36642937 CDK9 ChIP and functional analyses reason for a prominent role of CDK9 itself and elongation factor complexes PAF1c and SEC involved in pause and elongation control. human lymph Low throughput The Establishment of a Hyperactive Structure Allows the Tumour Suppressor Protein p53 to Function through P-TEFb during Limited CDK9 Kinase Inhibition Tumour T cell E_02_0838 ChIP,qPCR "Our ChIP experiments showed that prior to activation p53 was exclusively found at the upstream enhancer that harbors a high-affinity, near-consen_x0002_sus binding site for p53 (Fig 5A). Occupancy of this site increased incrementally after 1.5 and 4 hours of CDK9 inhibition (Fig 5B). In contrast to this pre-loaded ""primary"" enhancer, treat_x0002_ment with 067 was followed by de novo recruitment of p53 to additional, secondary binding sites, most notably to an intronic region that maps to position +4 kb downstream of the p21 TSS and contains another near-consensus p53 motif (Fig 5A). After four hours of treatment,p53 occupancy of this site reached similar levels as found at the upstream enhancer (Fig 5B)." Enhancer -- ChIP-qPCR CAP20, CDKN1, CIP1, MDA-6,?P21, SDI1, WAF1, p21CIP1 -- -- -- BCC7, BMFS5, LFS1,?P53, TRP53 qPCR -- -- CDKN1A,CDKN1A TP53,TP53 "Our ChIP experiments showed that prior to activation p53 was exclusively found at the upstream enhancer that harbors a high-affinity, near-consen_x0002_sus binding site for p53 (Fig 5A). Occupancy of this site increased incrementally after 1.5 and 4 hours of CDK9 inhibition (Fig 5B). In contrast to this pre-loaded ""primary"" enhancer, treat_x0002_ment with 067 was followed by de novo recruitment of p53 to additional, secondary binding sites, most notably to an intronic region that maps to position +4 kb downstream of the p21 TSS and contains another near-consensus p53 motif (Fig 5A). After four hours of treatment,p53 occupancy of this site reached similar levels as found at the upstream enhancer (Fig 5B).;Our ChIP experiments showed that prior to activation p53 was exclusively found at the upstream enhancer that harbors a high-affinity, near-consen_x0002_sus binding site for p53 (Fig 5A). Occupancy of this site increased incrementally after 1.5 and 4 hours of CDK9 inhibition (Fig 5B). In contrast to this pre-loaded ""primary"" enhancer, treat_x0002_ment with 067 was followed by de novo recruitment of p53 to additional, secondary binding sites, most notably to an intronic region that maps to position +4 kb downstream of the p21 TSS and contains another near-consensus p53 motif (Fig 5A). After four hours of treatment,p53 occupancy of this site reached similar levels as found at the upstream enhancer (Fig 5B)." MCF7 cells, which harbour functional wild-type p53, were treated for 20 minutes to 4 hours with 10 μM 067 and both nascent unspliced precursor (pre) and mature spliced mRNA was analyzed by quantitative PCR (qPCR). Inhibitor treatment led to significant(2.5-fold) repression of nascent RNA synthesis of the p53 target gene p21 within 20 minutes (Fig1A).;MCF7 cells, which harbour functional wild-type p53, were treated for 20 minutes to 4 hours with 10 μM 067 and both nascent unspliced precursor (pre) and mature spliced mRNA was analyzed by quantitative PCR (qPCR). Inhibitor treatment led to significant(2.5-fold) repression of nascent RNA synthesis of the p53 target gene p21 within 20 minutes (Fig1A). 26728555 chr12 109528035 109532509 AFF3 Here, we report that AFF3 can specifically bind both gametic DMRs (gDMRs) and enhancers within imprinted loci in an allele-specific manner. human Low+High throughput Regulation of the imprinted Dlk1-Dio3 locus by allele-specific enhancer activity 否 -- embryonic stem cell E_02_0839 ChIP-seq,ChIP By performing ChIP-seq in different mESC lines and using two different antibodies, we were able to identify 973 high-confidence AFF3-binding sites.AFF3 is also de_x0002_tected in the intergenic regions within the Dlk1-Dio3 locus, which harbors a paternally methylated gDMR/ ICR (Fig. 1A). Two discrete AFF3-binding sites are located 12 kb (distal AFF3 peak) and 10 kb (proximal AFF3 peak)upstream of the promoter region of the maternally ex_x0002_pressed gene Meg3 (Fig. 1B).This AFF3 peak resides within the intergenic DMR (IG-DMR) of the Dlk1-Dio3 cluster and corresponds to the Meg3-proximal enhancer peak located just 2.4 kb from the Meg3-distal gDMR peak (Figs. 1B, 3A). While bisulfite sequencing of ChIP DNA demonstrated that AFF3 is on the inactive allele at the Meg3-distal gDMR,AFF3 is restricted to the unmethylated allele at the Meg3-proximal enhancer (Fig. 3B,C; Supplemental Fig. S4). Enhancer -- ChIP-seq,ChIP 2900016C05Rik,3110050O07Rik,6330408G06Rik,AI425946,AW108224,D12Bwg1266e,Gtl2,R74756,R75394 -- -- -- LAF4,MLLT2-like ChIP,ChIP-seq -- -- Meg3 Aff3 This AFF3 peak resides within the intergenic DMR (IG-DMR) of the Dlk1-Dio3 cluster and corresponds to the Meg3-proximal enhancer peak located just 2.4 kb from the Meg3-distal gDMR peak (Figs. 1B, 3A). While bisulfite sequencing of ChIP DNA demonstrated that AFF3 is on the inactive allele at the Meg3-distal gDMR,AFF3 is restricted to the unmethylated allele at the Meg3-proximal enhancer (Fig. 3B,C; Supplemental Fig. S4). This AFF3 peak resides within the intergenic DMR (IG-DMR) of the Dlk1-Dio3 cluster and corresponds to the Meg3-proximal enhancer peak located just 2.4 kb from the Meg3-distal gDMR peak (Figs. 1B, 3A). While bisulfite sequencing of ChIP DNA demonstrated that AFF3 is on the inactive allele at the Meg3-distal gDMR,AFF3 is restricted to the unmethylated allele at the Meg3-proximal enhancer (Fig. 3B,C; Supplemental Fig. S4).Knockdown of AFF3 leads to reduced H3K27ac at the Meg3-proximal enhancer, indicating that AFF3 is required to maintain its active chromatin state (Fig. 3D; Supple_x0002_mental Table 2). Furthermore, the expression levels of Meg3 and the downstream maternally expressed noncod_x0002_ing genes within the Dlk1-Dio3 locus are also reduced in AFF3 knockdown ESCs (Fig. 3E; Supplemental Fig. S5A),suggesting that an activating function of AFF3 might beexerted from the nearby Meg3-proximal enhancer. 26673704 chr7 117038917 117040917 CFTR We showed previously that intronic and ex_x0002_tragenic enhancers, when occupied by specific tran_x0002_scription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. human lung Low throughput Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus -- Caco-2,Calu3 cell E_02_0840 RT-qPCR,4C,ChIP,CRISPR/Cas9 Two pairs of gRNAs ?anking the ?20.9 kb CTCF site and the intron 11 enhancer core were identifed using the CRISPR Design Program Enhancer CRISPR/Cas9 -- ABC35,ABCC7,CF,CFTR/MRP,MRP7,TNR-CFTR,dJ760C5.1 -- -- -- HNF3A,TCF3A,HNF3B,TCF3B,HNF-1A,HNF1,HNF4A,IDDM20,LFB1,MODY3,TCF-1,TCF1,CDX-3/AS, CDX3, CDX2 4C,ChIP,CRISPR/Cas9 -- -- CFTR FOXA1,FOXA2,HNF1A,CDX2 Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and siRNA-mediated depletion of architectural proteins to determine the relative contribution of structural elements and enhancers to the higher order structure and expression of the CFTR locus. Approximately 1.2 encompass_x0002_ing the binding sites for critical transcription factors driving the intron 11 Enhancer (FOXA1/2,HNF1 and CDX2). 26673693 chr14 54227135 54228033 Ets1 We found that while Ets1 binding at distal sites was associated with active genes at both DN and DP stages, its enhancer activity was attained at the DP stage, as reflected by levels of the core transcriptional hallmarks H3K4me1/3, RNA Polymerase II and eRNA. This dual, stage-specific ability reflected a switch from non-T hematopoietic toward T-cell specific gene expression programs during the DN-to-DP transition, as indicated by transcriptome analyses of Ets1(-/-) thymic cells. Coincidentally, Ets1 associates more specifically with Runx1 in DN and with TCF1 in DP cells. We also provide evidence that Ets1 predominantly binds distal nucleosome-occupied regions in DN and nucleosome-depleted regions in DP. Finally and importantly, we demonstrate that Ets1 induces chromatin remodeling by displacing H3K4me1-marked nucleosomes. Our results thus provide an original model whereby the ability of a transcription factor to bind nucleosomal DNA changes during differentiation with consequences on its cognate enhancer activity. mouse epithelial Low+High throughput Dynamic recruitment of Ets1 to both nucleosome-occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation 否 -- P5424,CD4+ CD8+ DP cell E_02_0841 ChIP-seq,ChIP We found that eRNAs essentially reca_x0002_pitulated Pol II patterns during DN to DP transition as wellas those of Ets1 in DP only, suggesting highest enhancer ac_x0002_tivity in class 4 at the DN stage and classes 4–5 at the DP stage (Figure 3C). Thus, distal Ets1 enhancers broadly re_x0002_cruit Pol II that is able to generate paused transcripts.Significance of gene expression differences by increasing Ets1-fold change. Expression fold changes for all classes, shown as a boxplot. Significance levels for each comparison are indicated above, with 1 star denoting P < 0.05, 2 stars denoting P < 0.01 and 3 stars denoting P < 0.005. Enhancer -- ChIP-seq,Western blot,ChIP-qPCR AI323713 -- -- -- AI196000,AI448617,D230050P06,Ets-1,Tpl1,p54,vs,AI465550,TCF-1,Tcf1,AML1,CBF-alpha-2,Cbfa2,Pebp2a2,Pebpa2b ChIP-qPCR,Western blot -- -- Dad1,Dad1,Dad1,Dad1,Dad1,Dad1 Ets1,Tcf1,Runx1,Ets1,Tcf1,Runx1,Ets1,Tcf1,Runx1,Ets1,Tcf1,Runx1,Ets1,Tcf1,Runx1,Ets1,Tcf1,Runx1 We further validated the dy_x0002_namic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.UCSC genome browser screenshot of the Tcra (left) and Cd2 loci (right)showing increased H3K4me1 signal at the Ets1 binding site following knockdown in the P5424 cell line.;We further validated the dy_x0002_namic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.UCSC genome browser screenshot of the Tcra (left) and Cd2 loci (right)showing increased H3K4me1 signal at the Ets1 binding site following knockdown in the P5424 cell line.;We further validated the dy_x0002_namic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.UCSC genome browser screenshot of the Tcra (left) and Cd2 loci (right)showing increased H3K4me1 signal at the Ets1 binding site following knockdown in the P5424 cell line.;We further validated the dy_x0002_namic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.UCSC genome browser screenshot of the Tcra (left) and Cd2 loci (right)showing increased H3K4me1 signal at the Ets1 binding site following knockdown in the P5424 cell line.;We further validated the dy_x0002_namic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.UCSC genome browser screenshot of the Tcra (left) and Cd2 loci (right)showing increased H3K4me1 signal at the Ets1 binding site following knockdown in the P5424 cell line.;We further validated the dy_x0002_namic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.UCSC genome browser screenshot of the Tcra (left) and Cd2 loci (right)showing increased H3K4me1 signal at the Ets1 binding site following knockdown in the P5424 cell line. We further validated the dynamic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.;We further validated the dynamic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.;We further validated the dynamic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.;We further validated the dynamic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.;We further validated the dynamic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes.;We further validated the dynamic recruitment of TCF1 and Runx1 by ChIP-qPCR at the Tcra Enhancer, which is bound by similar levels of Ets1 in both DN and DP thymocytes. 26663721 chr12 85515101 85543901 GC We conclude that enhancer divergence underlies the difference in transcriptional activation after GC treatment between mouse and human macrophages. Only the shared inducible loci show evidence of selection, and therefore these loci may be important for the subset of responses to GC that is shared between species. human connective Low+High throughput Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages 否 -- Peripheral blood mononuclear cell E_02_0842 ChIP-seq To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM. Enhancer -- ChIP-seq D12Rfj1,c-fos,cFos,Jundm2,Jundp2,TIF -- -- -- -- -- -- -- Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2?,Fos-Jdp2? --,--,--,--,--,--,--,--,-- To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM.;To identify the sites involved in the GC response in the two species,Chromatin immunoprecipitation for GR and sequencing (ChIP-seq) was performed 2 h after dexamethasone treatment in both mBMDM and hMDM. Representative UCSC browser tracks for GR binding in mBMDM and hMDM are shown in Fig. 2A and 2C.ChIP-seq data tracks from the UCSC browser for the Fos – Jdp2 region, for GR binding in mBMDM. Data from ChIP with anti-GR antibodies after treatment with 100nM dexamethasone for 2h (Dex GR IP), input material (Dex input) and immunoprecipitated material from a vehicle treated control (Vehicle GR IP) are shown. Enriched motifs found de novo within GR bound sites in mBMDM and hMDM. --;--;--;--;--;--;--;--;-- 26659182 chr2 168744572 168752225 Chaf1a To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting. mouse epithelial Low+High throughput The histone chaperone CAF-1 safeguards somatic cell identity 否 -- MEF,iPS,ES,MEFs,HSP cell E_02_0843 ChIP-seq,ATAC-seq,CRISPR/Cas9 To validate these observations with an independent, higher resolution method, we performed Assay of Transposase Accessible Chromatin using sequencing (ATAC-seq), which detects integration of the Tn5 transposase in open chromatin regions27 (Extended Data Fig. 7c). Consistent with the SONO-seq data, ATAC-seq analysis of early reprogramming intermediates showed a more accessible chromatin configuration at regulatory regions including ESC-specific enhancers upon suppression of Chaf1a (Fig. 5a; P value <10?15). Moreover, Chaf1a knockdown caused a significant increase in chromatin accessibility across ESC-specific super-enhancers at day 3 of iPSC formation (Supplementary Table 3 and Extended Data Fig. 7d,e; P value <5.3×10?16). Of note, super-enhancers linked to specialized cell types such as macrophages, lymphocytes and muscle cells were also significantly more accessible in Chaf1a depleted reprogramming intermediates compared to controls (Extended Data Fig. 7f). Super-Enhancer -- ChIP-seq,ATAC-seq 5730441M18Rik,AA407717,AL022809,AW536104,C330011P20Rik,C78083,C78563,Tex20 -- -- -- Sox-2,lcc,ysb ChIP-seq,ATAC-seq -- -- Sall4,Sall4,Sall4,Sall4,Sall4,Sall4,Sall4,Sall4,Sall4,Sall4,Sall4,Sall4 Sox2,Sox2,Sox2,Sox2,Sox2,Sox2,Sox2,Sox2,Sox2,Sox2,Sox2,Sox2 Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation.;Moreover,Chaf1a knockdown caused a significant increase in Chromatin accessibility across ES-cell-specific Super-Enhancers at day 3 of iPS cell formation. Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. ;Next,we performed ChIP-seq analysis for Sox2 at day 3 of OKSM expression in order to test our hypothesis that increased Chromatin accessibility at Enhancer lements influences reprogramming factor binding. Of the Sox2-bound super-Enhancers unique to CAF-1 knockdown cells, a subset also showed a more accessible chromatin structure by ATAC-seq analysis. 26615198 chr7 117011495 117063767 CFTR We demonstrate that two of these novel interacting regions cooperatively increase CFTR expression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin looping via CTCF. human Nose, skin Low+High throughput Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements 否 Cystic Fibrosis adepithelial cell,skin fibroblast E_02_0844 Hi-C,5C,Luciferase Reporter Assay,PCR We tested whether any of the newly identiied looping regions displayed enhancer activity in a reporter assay. As shown in Figure 4A, two of our interacting regions significantly enhanced CFTR promoter activity.The fragment encompassing a DHS in the region E displayed a strong Enhancer function with almost 6-fold effect on the CFTR promoter. Enhancer -- Luciferase Reporter Assay ABC35,ABCC7,CF,CFTR/MRP,MRP7,TNR-CFTR,dJ760C5.1 -- -- -- -- -- -- -- CFTR -- As shown in Figure 4A, two of our interacting regions significantly enhanced CFTR promoter activity.The fragment encompassing a DHS in the region E displayed a strong Enhancer function with almost 6-fold effect on the CFTR promoter. -- 26595656 chr12 85433906 85439068 Fos Here we demonstrate that multiple enhancers surrounding the c-fos gene are crucial for ensuring robust c-fos response to various stimuli. Membrane depolarization, brain-derived neurotrophic factor (BDNF) and forskolin activate distinct subsets of the enhancers to induce c-fos transcription in neurons, suggesting that stimulus-specific combinatorial activation of multiple enhancers underlies the broad inducibility of the c-fos gene. Accordingly, the functional requirement of key transcription factors varies depending on the type of stimulation. Combinatorial enhancer activation also occurs in the brain. Providing a comprehensive picture of the c-fos induction mechanism beyond the minimal promoter, our study should help in understanding the physiological nature of c-fos induction in relation to neural activity and plasticity. mouse nervous Low+High throughput Stimulus-specific combinatorial functionality of neuronal c-fos enhancers 否 -- neuron,neuroglioform cell E_02_0845 ChIP-seq,Luciferase Reporter Assay These enhancers, which we identified in primary cultures of mouse cortical neurons, appear to be active in the intact brain throughout development, as all of them were tightly aligned with the chroma_x0002_tin immunoprecipitation (ChIP)-seq peaks of the active enhancer marker, acetylated H3K27 (H3K27ac)(Supplementary Fig. 1). Enhancer 3C -- D12Rfj1,c-fos,cFos These results demonstrate that the combinatorial activation of the c-fosenhancers enables the c-fos gene to be broadly responsive to various signaling pathways. CRISPRi,RT-qPCR We also evaluated the functionality of individual enhancers in their native context by targeted transcription silencing via CRISPR interference (CRISPRi). Using eRNA as a proxy for enhancer activity, we found that distinc_x0002_tive subsets of the c-fos enhancers are activated in the intact brain following chemically induced seizure or light stimulation. CREB,CREB-1,MCM1,ADCAD1,RSRFC4,RSRFC9,mef2,C5DELq14.3,DEL5q14.3,Le-PAS,NXF,PASD10,bHLHe79 ChIP-seq -- -- Fos,Fos,Fos,Fos,Fos,Fos,Fos,Fos,Fos Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4,Creb,srf,Mef2a,Mef2d,Mef2c,Npas4 Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers.;Characterizing individual c-fos Enhancers by chromosome-conformation capture (3C) analysis and an Enhancer reporter assay, we have corroborated the idea that eRNA is a reliable marker for identifying activated Enhancers. ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5).;ChIP-_x0002_seq analysis has revealed that the c-fos promoter and enhancers were bound by different combinations of several activity-regulated TFs6 (Supplementary Fig. 1).Knockdown of CREB, MEF2A and NPAS4 significantly impaired c-fos induction by Cl-mediated membrane depolarization (Fig. 4a and Supplementary Fig. 4). Although knockdown of MEF2 family members MEF2D and MEF2C showed a slight decrease in c-fos expression, it was not significant and had a weaker impact than MEF2A knockdown. The decrease in c-fos expression was paralleled with little effect on eRNA transcription (Supplementary Fig. 5). 26581162 chr3 108015219 108015290 CD83 CD83 is a marker for T-cell activation,41 and the observed presence of upregulated CD83 points to TNFα's potential T-cell–activating role not observed in sg362F/dCas9-VP64 transfected cells. human lymph Low throughput Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex -- 293T cell E_02_0846 Luciferase Reporter Assay,Transient Transfection Assay,RNA-seq,PCR In this study, we identify a targeted hotspot for CRISPR acti_x0002_vation within the long terminal repeat (LTR) enhancer region,at the junction between two nuclear factor (NF)-κB transcrip_x0002_tion factor–binding sites.Twenty-three possible NGG Streptococcus pyogenes(Sp) Cas9 photospacer adjacent motif (PAM) sites for targeting of sgRNAs were identified in the U3 region of the LTR, upstream of the HIV transcriptional start site(TSS) (?450 to 0 bp; HIV genome HXB2) within the enhancer and modulatory region of the promoter. Enhancer CRISPR/Cas9 Luciferase Reporter Assay B7-H5,B7-H7,B7H7,B7y -- -- -- CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NFKB-p105,NFKB-p50,NFkappaB,p105,p50 CRISPR/Cas9 -- -- HHLA2 NFKB1 All sgRNAs were named according to the 3′ adjacent sense strand nucleotide cleavage site catalyzed by nuclease-active Cas9 (Figure? 1a) and were screened together with dCas9-VP64 or dCas9-VP160 for their activation properties by transient transfection with the reporter NL4-3.Luc.R_x005f_x0002_E-，a full-length HIV molec_x0002_ular clone where luciferase is driven by the viral LTR. Since sg362F fully occupies the sequence across both NF-κB–binding sites, we next determined if CRISPR activation via the sg362F target site was coupled to NF-κB function. these data strongly support a conclusion where sg362F/dCas9-VP64 functions independently of NF-κB as a stand-alone transactivator of LTR activation. 26560027 chr11 8271697 8279492 LMO1 These findings indicate that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells. human Low+High throughput Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism 相关 Neuroblastoma neuroblastoma cell lines E_02_0847 ChIP-seq,Luciferase Reporter Assay Acetylation of histone H3 at lysine 27 (H3K27ac) is a hallmark of active enhancers, and ChIP-seq analysis of SHSY5Y (G/G; not MYCN amplified), KELLY (G/?; MYCN amplified), BE2 (G/T; MYCN amplified) and NGP (G/T; MYCN amplified) neuroblastoma cells showed extensive H3K27 acetylation in the first intron of LMO1 across rs2168101, which was not observed in BE2C (T/? ; MYCN amplified; Fig. 3c). This region is classified as a super-enhancer in G-allele-containing lines SHSY5Y, KELLY and BE2 based on enhancer clustering and especially high H3K27ac signal (NGP was just below the threshold; see Methods), a pattern also observed for other known oncogenes and tumour suppressor genes in this disease12 (Fig. 3d and Extended Data Fig. 6a). We next performed luciferase reporter assays to measure the effect of rs2168101 alleles on enhancer activity. HEK293T cells transfected with constructs containing the risk G allele demonstrated 30–300-fold higher normalized luminescence compared to the T allele (t-test P = 0.002, Fig. 3e), whereas luciferase activity of the T allele was not significantly different from empty vector, indicating that the intact GATA motif is required for robust enhancer activity. Super-Enhancer -- ChIP-seq,Luciferase Reporter Assay RBTN1,RHOM1,TTG1 -- -- -- HDR, HDRS Luciferase Reporter Assay,RNAi -- -- LMO1 GATA3 Acetylation of histone H3 at lysine 27 (H3K27ac) is a hallmark of active enhancers, and ChIP-seq analysis of SHSY5Y (G/G; not MYCN amplified), KELLY (G/?; MYCN amplified), BE2 (G/T; MYCN amplified) and NGP (G/T; MYCN amplified) neuroblastoma cells showed extensive H3K27 acetylation in the first intron of LMO1 across rs2168101, which was not observed in BE2C (T/? ; MYCN amplified; Fig. 3c). This region is classified as a super-enhancer in G-allele-containing lines SHSY5Y, KELLY and BE2 based on enhancer clustering and especially high H3K27ac signal (NGP was just below the threshold; see Methods), a pattern also observed for other known oncogenes and tumour suppressor genes in this disease12 (Fig. 3d and Extended Data Fig. 6a). We next performed luciferase reporter assays to measure the effect of rs2168101 alleles on enhancer activity. HEK293T cells transfected with constructs containing the risk G allele demonstrated 30–300-fold higher normalized luminescence compared to the T allele (t-test P = 0.002, Fig. 3e), whereas luciferase activity of the T allele was not significantly different from empty vector, indicating that the intact GATA motif is required for robust enhancer activity. HEK293T cells transfected with constructs containing the risk G allele demonstrated 30–300-fold higher normalized luminescence compared to the T allele (t-test P = 0.002, Fig. 3e), whereas luciferase activity of the T allele was not significantly different from empty vector, indicating that the intact GATA motif is required for robust enhancer activity. Finally, knockdown of GATA3 in SHSY5Y and KELLY cells resulted in both decreased LMO1 protein levels and suppression of cell growth that was rescued by LMO1 overexpression (Fig. 3f and Extended Data Fig. 7), indicating the central role of GATA3 in regulating LMO1 expression levels in neuroblastoma.Finally, knockdown of GATA3 in SHSY5Y and KELLY cells resulted in both decreased LMO1 protein levels and suppression of cell growth that was rescued by LMO1 overexpression (Fig. 3f and Extended Data Fig. 7), indicating the central role of GATA3 in regulating LMO1 expression levels in neuroblastoma. 26550034 chr4 55565908 55608014 KAT5 The genome-wide mapping of Tip60 binding in mESCs by chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) shows that the Tip60 complex is present at promoter regions of predominantly active genes that are bound by RNA polymerase II (Pol II) and contain the H3K4me3 histone mark. The coactivator HAT complexes, Tip60- and Mof (KAT8)-containing (NSL and MSL), show a global overlap at promoters, whereas distinct binding profiles at enhancers suggest different regulatory functions of each essential HAT complex. Interestingly, Tip60 enrichment peaks at about 200 bp downstream of the transcription start sites suggesting a function for the Tip60 complexes in addition to histone acetylation. The comparison of genome-wide binding profiles of Tip60 and c-Myc, a somatic cell reprogramming factor that binds predominantly to active genes in mESCs, demonstrate that Tip60 and c-Myc co-bind at 50–60 % of their binding sites. We also show that the Tip60 complex binds to a subset of bivalent developmental genes and defines a set of mESC specific enhancer as well as super-enhancer regions. human epithelial Low+High throughput Tip60 complex binds to active PolII promoters and a subset of enhancers and co-regulates the c-Myc network in mouse embryonic stem cells 否 -- E14,CD1 feeder cell,wt cell E_02_0848 ChIP-seq,ChIP The genome-wide mapping of Tip60 binding in mESCs by chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) shows that the Tip60 complex is present at promoter regions of predominantly active genes that are bound by RNA polymerase II (Pol II) and contain the H3K4me3 histone mark. The coactivator HAT complexes, Tip60- and Mof (KAT8)- containing (NSL and MSL), show a global overlap at promoters, whereas distinct binding profiles at enhancers suggest different regulatory functions of each essential HAT complex. Interestingly, Tip60 enrichment peaks at about 200 bp downstream of the transcription start sites suggesting a function for the Tip60 complexes in addition to histone acetylation. Super-Enhancer -- ChIP-seq EZF,Gklf,Zie -- -- -- AI839539,CPLA2,Htatip,Htatip1,PLIP,Tip55,Tip60 ChIP-qPCR,ChIP-seq -- -- Klf4,Klf4,Klf4,Klf4,Klf4,Klf4,Klf4 Kat5,Kat5,Kat5,Kat5,Kat5,Kat5,Kat5 As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b).;As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b).;As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b).;As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b).;As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b).;As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b).;As two of the so-called ‘super Enhancer’ regions of the Nanog gene and the Enhancer of the Klf4 gene are bound by Tip60,but not by Nsl1 and Msl1(Fig.?7a, b). The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific.;The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific.;The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific.;The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific.;The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific.;The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific.;The validation of several randomly selected ChIP-seq positive sites by ChIP-qPCR indicated specific Tip60 enrichments at these sites, when compared to control IgG ChIP signals and to background enrichment at an intergenic region negative for Tip60 binding (Fig.?1b).These results, together with the ChIP-qPCR validation (Fig.? 1b), indicate that the obtained anti-Tip60 ChIP-seq signal is specific. 26537192 chr4 29115647 29140947 Lef1 To get insight into the mechanism of how EphA7 gene expression is regulated during the dorsal specification of the dien- and mesencephalon, we investigated the cis-acting regulatory sequence driving EphA7 to the dorsal midline of the dien- and mesencephalon. Transgenic LacZ reporter analysis, using overlapping EphA7 BACs, was used to narrow down the dorsal midline-specific enhancer, revealing the 25.3 kb genomic region as the enhancer candidate. Strikingly, this genomic DNA was located far downstream of the EphA7 transcription start site, +302.6 kb to +327.9 kb. Further enhancer mapping, using comparative genomic analysis and transgenic methods, showed that the 187 bp genomic DNA alone, approximately 305 kb downstream of the EphA7 transcription start site, was sufficient to act as the dorsal midline-specific enhancer of EphA7. Importantly, our results indicate that the 187 bp dorsal midline-specific enhancer is critically regulated by homeobox transcription factors during the development of the dien- and mesencephalon. mouse nervous Low throughput Identification of the 187 bp EphA7 Genomic DNA as the Dorsal Midline-Specific Enhancer of the Diencephalon and Mesencephalon 否 -- neural cell E_02_0849 PCR,Transgenic mice Transgenic LacZ reporter analysis, using overlapping EphA7 BACs, was used to narrow down the dorsal midline-specific enhancer, revealing the 25.3 kb genomic region as the enhancer candidate. Strikingly, this genomic DNA was located far downstream of the EphA7 transcription start site, +302.6 kb to +327.9 kb. Enhancer -- PCR,Transgenic mice Cek11,Ebk,Ehk3,Hek11,Mdk1 The 187 bp dorsal midline-specific enhancer is critically regulated by homeobox transcription factors during the development of the dien- and mesencephalon. PCR Importantly, we found that transgenic embryos carrying ECR3, but not ECR1 or 2, displayed LacZ expression in the dorsal midline of the dien- and mesencephalon ECR3 PCR -- -- Epha7,Epha7,Epha7 Sbe3,Sbe3,Sbe3 Further enhancer mapping, using comparative genomic analysis and transgenic methods, showed that the 187 bp genomic DNA alone, approximately 305 kb downstream of the EphA7 transcription start site, was sufficient to act as the dorsal midline-specific enhancer of EphA7.;Further enhancer mapping, using comparative genomic analysis and transgenic methods, showed that the 187 bp genomic DNA alone, approximately 305 kb downstream of the EphA7 transcription start site, was sufficient to act as the dorsal midline-specific enhancer of EphA7.;Further enhancer mapping, using comparative genomic analysis and transgenic methods, showed that the 187 bp genomic DNA alone, approximately 305 kb downstream of the EphA7 transcription start site, was sufficient to act as the dorsal midline-specific enhancer of EphA7. To investigate whether the conserved transcription factor binding sites are functionally important for the 187 bp ECR3 enhancer activity, three putative transcription factor binding sites were selected for deletion. The deleted ECR3 DNA was examined for its effect on the enhancer activity by creating transgenic mouse embryos (Figs. 4A and 4B).;To investigate whether the conserved transcription factor binding sites are functionally important for the 187 bp ECR3 enhancer activity, three putative transcription factor binding sites were selected for deletion. The deleted ECR3 DNA was examined for its effect on the enhancer activity by creating transgenic mouse embryos (Figs. 4A and 4B).;To investigate whether the conserved transcription factor binding sites are functionally important for the 187 bp ECR3 enhancer activity, three putative transcription factor binding sites were selected for deletion. The deleted ECR3 DNA was examined for its effect on the enhancer activity by creating transgenic mouse embryos (Figs. 4A and 4B). 26505625 chr7 95210132 95260132 MET The exonic single nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). human Low+High throughput Validation and genomic interrogation of the MET variant rs11762213 as a predictor of adverse outcomes in clear cell renal cell carcinoma 是 Clear Cell Renal Cell Carcinoma ccRCC cell E_02_0850 ChIP,ChIP-seq rs11762213 alone is found in a regulatory element of MET likely in an enhancer domain, and this has implications for its interaction both with MET itself and with potentially other cis-acting target genes.To further characterize the functional significance of rs11762213 we used our previously generated genome-wide chromatin annotation maps using cultured human proximal tubular epithelial cells (HKC8) and overlaid them with previously generated gene regulatory annotation maps from a panel of ChIP-seq data using the hidden Markov model-based ChromHMM chromatin segmentation program (Figure 4). Notably, rs11762213 maps to an H3K4me1 histone modification mark, which serves as an enhancer marker and is therefore consistent with the hypothesis that the SNP has a regulatory function.Mapping of rs11762213 to regulatory regions within the genome suggests that it may impact a DNA enhancer region. Enhancer -- ChIP,RNA-seq AI838057,HGF,HGFR,Par4,c-Met -- -- -- -- -- -- -- MET -- Next, we assessed the impact of rs11762213 on MET steady-state mRNA and protein tumor expression using available RNA seq data and reverse phase protein array (RPPA) data from the TCGA. We found no difference in tumor MET expression by SNP status (p=0.47 Mann Whitney) including all detected MET isoforms (n=18) (Supplemental figure 2A). Since rs11762213 is located in the coding region of exon 2 we further explored exon level expression differences by genotype and again did not find any difference by genotype for exon 2 MET expression (p=0.29) of any other exon (Supplemental figure 3). Additionally, we did not see differences in tumor MET protein (p=0.88) or MET phospho-protein expression (Y1235) (Supplemental figure 2B and 2C).rs11762213 was associated with higher normal tissue MET expression (p=0.019), however, in an independent normal kidney Affymetrix mRNA array data set this finding did not validate (n=95) (data not shown). -- 26494787 chr10 61403948 61408233 Lhx1 Here we demonstrate Smad4/Eomes-dependent Lhx1 expression in the epiblast marks the entire definitive endoderm lineage, the anterior mesendoderm, and midline progenitors. Conditional inactivation of Lhx1 disrupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. Moreover, in proteomic experiments, we characterized a complex comprised of Lhx1, Otx2, and Foxa2 as well as the chromatin-looping protein Ldb1. These partnerships cooperatively regulate development of the anterior mesendoderm, node, and midline cell populations responsible for establishment of the left-right body axis and head formation. mouse epithelial Low+High throughput Lhx1 functions together with Otx2, Foxa2,and Ldb1 to govern anterior mesendoderm,node, and midline development 否 -- embryonic stem cell E_02_0851 ChIP,ChIP-seq ChIP (red) and input (blue) wiggle plot overlays showing enrichment of Lhx1 ChIP-seq density at Hesx1,Fzd8,Embigin,Nodal,Otx2,and Foxa3. Purple boxes indicate the positions of previously mapped Nodal Enhancer elements. Enhancer -- ChIP,ChIP-seq Tg.413d -- -- -- Lim1,C77258,TBR-2,Tbr2 ChIP -- -- Nodal,Nodal,Nodal,Nodal,Nodal,Nodal Lhx1,Eomes,Lhx1,Eomes,Lhx1,Eomes,Lhx1,Eomes,Lhx1,Eomes,Lhx1,Eomes Conditional inactivation of Lhx1 dis_x0002_rupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunopre_x0002_cipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. ;Conditional inactivation of Lhx1 dis_x0002_rupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunopre_x0002_cipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. ;Conditional inactivation of Lhx1 dis_x0002_rupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunopre_x0002_cipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. ;Conditional inactivation of Lhx1 dis_x0002_rupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunopre_x0002_cipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. ;Conditional inactivation of Lhx1 dis_x0002_rupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunopre_x0002_cipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. ;Conditional inactivation of Lhx1 dis_x0002_rupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunopre_x0002_cipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. Several putative Lhx1 target genes were represented in our ChIP data set. For example, Lhx1 binding was detected at two distinct regions at the Hesx1 locus, including a regulatory element in the 5′ untranslated region (containing two Lhx1-binding motifs) and a 3′ distal enhancer. Lhx1 ChIP peaks were also present upstream of Embigin exon 1.;Several putative Lhx1 target genes were represented in our ChIP data set. For example, Lhx1 binding was detected at two distinct regions at the Hesx1 locus, including a regulatory element in the 5′ untranslated region (containing two Lhx1-binding motifs) and a 3′ distal enhancer. Lhx1 ChIP peaks were also present upstream of Embigin exon 1.;Several putative Lhx1 target genes were represented in our ChIP data set. For example, Lhx1 binding was detected at two distinct regions at the Hesx1 locus, including a regulatory element in the 5′ untranslated region (containing two Lhx1-binding motifs) and a 3′ distal enhancer. Lhx1 ChIP peaks were also present upstream of Embigin exon 1.;Several putative Lhx1 target genes were represented in our ChIP data set. For example, Lhx1 binding was detected at two distinct regions at the Hesx1 locus, including a regulatory element in the 5′ untranslated region (containing two Lhx1-binding motifs) and a 3′ distal enhancer. Lhx1 ChIP peaks were also present upstream of Embigin exon 1.;Several putative Lhx1 target genes were represented in our ChIP data set. For example, Lhx1 binding was detected at two distinct regions at the Hesx1 locus, including a regulatory element in the 5′ untranslated region (containing two Lhx1-binding motifs) and a 3′ distal enhancer. Lhx1 ChIP peaks were also present upstream of Embigin exon 1.;Several putative Lhx1 target genes were represented in our ChIP data set. For example, Lhx1 binding was detected at two distinct regions at the Hesx1 locus, including a regulatory element in the 5′ untranslated region (containing two Lhx1-binding motifs) and a 3′ distal enhancer. Lhx1 ChIP peaks were also present upstream of Embigin exon 1. 26445536 chr22 35686840 35687280 MAF Interestingly, Bach1, a nuclear protein shown to associate with small MAF proteins and serve as a repressor of HO-1 gene expression human blood Low throughput Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells -- Endothelial cell E_02_0852 ChIP,RT-PCR,qPCR To investigate whether the translocated Nrf2 interacted with the HO-1 promoter region, the primer sets for the enhancer region (E2) and promoter region near transcription start site were synthesized for ChIP assays (Figure 5A, upper panel schematic). The ChIP analyses demonstrated that AuNP treatment significantly induced Nrf2 binding to the human HO-1 E2 enhancer region, but not to the promoter region near the transcription start site. The binding to the enhancer region was concentration dependent, as determined by RT-PCR and real-time PCR (Figure 5B and C). Enhancer -- ChIP,RT-PCR,qPCR HMOX1D,HO-1,HSP32,bK286B10 -- -- -- -- -- -- -- HMOX1 -- To investigate whether the translocated Nrf2 interacted with the HO-1 promoter region, the primer sets for the enhancer region (E2) and promoter region near transcription start site were synthesized for ChIP assays (Figure 5A, upper panel schematic). The ChIP analyses demonstrated that AuNP treatment significantly induced Nrf2 binding to the human HO-1 E2 enhancer region, but not to the promoter region near the transcription start site. The binding to the enhancer region was concentration dependent, as determined by RT-PCR and real-time PCR (Figure 5B and C). -- 26443845 chr16 49740654 49742654 GATA1 Here we examined whether enhancers physically contact the gene segments transcribed by RNAPII.Initial results at the β-globin locus are consistent with elongation-dependent LCR–β-globin gene body contacts.To overcome the inherent resolution limitations of chromosome conformation capture (3C) studies associated with a small gene such as β-globin,we carried out our studies at the Kit locus. His locus has a well-characterized enhancer residing 114 kb upstream of the transcription start site (TSS),and its coding region encompasses∼82 kb,thus lending itself to finely space- and time-resolved 3C analysis (Jing et al. 2008). Using timed elongation block and release experiments,we found that the−114 enhancer forms stable contacts with the promoterproximal region throughout transcription elongation. Notably,additional dynamic contacts of the enhancer with the coding region were observed at the positions of elongating RNAPII.Similar dynamic enhancer gene body contacts were identified at the CD47 locus.These results are compatible with a dynamic folding pattern during transcription elongation in which the gene body is reeled past a stable enhancer–promoter complex,providing a physical platform upon which enhancers might impact on transcription elongation. human connective Low throughput Dynamic enhancer–gene body contacts during transcription elongation 否 -- G1E cell E_02_0853 RT-qPCR,ChIP CD47 gene contacts with its distal enhancer at ?80 kb dur_x0002_ing synchronized transcriptional elongation. (A) Map of the CD47 lo_x0002_cus. Blue bars indicate fragments of BglII, and red bars indicate the regions used for ChIP and RT-qPCR. Enhancer 3C RT-qPCR,ChIP 9130415E20Rik,AA407862,AI848868,AW108519,B430305P08Rik,IAP,Itgp -- -- -- -- -- -- -- Cd47,Cd47,Cd47,Cd47 --,--,--,-- This locus has a well-character- ized Enhancer residing 114 kb upstream of the transcrip- tion start site (TSS),and its coding region encompasses ～82 kb,thus lending itself to finely space-and time-re- solved 3C analysis (Jing et al. 2008) No- tably,additional dynamic contacts of the Enhancer with the coding region were observed at the positions of elon- gating RNAPII. Similar dynamic Enhancer gene body con- tacts were identified at the CD47 locus.CD47 gene contacts with its distal enhancer at ?80 kb dur_x0002_ing synchronized transcriptional elongation. (A) Map of the CD47 lo_x0002_cus. Blue bars indicate fragments of BglII, and red bars indicate the regions used for ChIP and RT-qPCR.;This locus has a well-character- ized Enhancer residing 114 kb upstream of the transcrip- tion start site (TSS),and its coding region encompasses ～82 kb,thus lending itself to finely space-and time-re- solved 3C analysis (Jing et al. 2008) No- tably,additional dynamic contacts of the Enhancer with the coding region were observed at the positions of elon- gating RNAPII. Similar dynamic Enhancer gene body con- tacts were identified at the CD47 locus.CD47 gene contacts with its distal enhancer at ?80 kb dur_x0002_ing synchronized transcriptional elongation. (A) Map of the CD47 lo_x0002_cus. Blue bars indicate fragments of BglII, and red bars indicate the regions used for ChIP and RT-qPCR.;This locus has a well-character- ized Enhancer residing 114 kb upstream of the transcrip- tion start site (TSS),and its coding region encompasses ～82 kb,thus lending itself to finely space-and time-re- solved 3C analysis (Jing et al. 2008) No- tably,additional dynamic contacts of the Enhancer with the coding region were observed at the positions of elon- gating RNAPII. Similar dynamic Enhancer gene body con- tacts were identified at the CD47 locus.CD47 gene contacts with its distal enhancer at ?80 kb dur_x0002_ing synchronized transcriptional elongation. (A) Map of the CD47 lo_x0002_cus. Blue bars indicate fragments of BglII, and red bars indicate the regions used for ChIP and RT-qPCR.;This locus has a well-character- ized Enhancer residing 114 kb upstream of the transcrip- tion start site (TSS),and its coding region encompasses ～82 kb,thus lending itself to finely space-and time-re- solved 3C analysis (Jing et al. 2008) No- tably,additional dynamic contacts of the Enhancer with the coding region were observed at the positions of elon- gating RNAPII. Similar dynamic Enhancer gene body con- tacts were identified at the CD47 locus.CD47 gene contacts with its distal enhancer at ?80 kb dur_x0002_ing synchronized transcriptional elongation. (A) Map of the CD47 lo_x0002_cus. Blue bars indicate fragments of BglII, and red bars indicate the regions used for ChIP and RT-qPCR. --;--;--;-- 26364592 chr10 78046488 78046636 Aire Here, we characterize a conserved noncoding sequence 1 (CNS1) containing two NF-κB binding sites upstream of the Aire coding region. We show that CNS1-deficient mice lack thymic expression of Aire and share several features of Aire-knockout mice, including downregulation of Aire-dependent genes, impaired terminal differentiation of the mTEC population, and reduced production of thymic Treg cells. In addition, we show that CNS1 is indispensable for RANK-induced Aire expression and that CNS1 is activated by NF-κB pathway complexes containing RelA. Together, our results indicate that CNS1 is a critical link between RANK signaling, NF-κB activation, and thymic expression of Aire. mouse epithelial Low throughput A highly conserved NF-κB-responsive enhancer is critical for thymic expression of Aire in mice 否 -- epithelial cell of thymus E_02_0854 qPCR To determine the in vivo function of the Aire enhancer region,we generated knockout mice (CNS1-KO) with a deletion of 45 bp within CNS1 including both NF-κB sites.We first studied thymic expression of Aire in purified thymic epithelial cell subsets-cTEC, mTEClo, and mTEChi-from homozygous CNS1-KO mice by qPCR targeting exons 7–9. Strik_x0002_ingly, Aire was not expressed in mTEChi from CNS1-KO mice,whereas the gene was highly expressed in mTEChi from WT mice(Fig. 2A). Enhancer -- qPCR,Immunofluorescence,RT-PCR Aire CNS1 is indispensable for RANK-induced Aire expression and that CNS1 is activated by NF-κB pathway complexes containing RelA. 3C,Luciferase Reporter Assay,EMSA To further examine the role of CNS1 in Aire gene regulation, we evaluated the spa_x0002_tial proximity between the CNS1 Enhancer and Aire promoter by chromosome conformation capture (3C) method.This result suggests that these distant regulatory regions are brought close to each other in intact chromatin. NF-KB1,NF-kappaB,NF-kappaB1,p105,p50,p50/p105 Luciferase Reporter Assay,EMSA -- -- Aire,Aire Nfkb1,Nfkb1 To determine whether the upstream CNS1 region regulates these variants, we analyzed the expression levels of the majority of exons in the Aire coding region by qPCR.Aire-KO mouse results are shown in Supporting Information Fig.2B), indicating that CNS1 is required for the thymic expression of the majority of, if not all, Aire splice variants.Deficiency of Aire protein expression was confirmed in situ by immunofluorescence staining, which showed no Aire protein in the thymi of CNS1-KO(Fig. 2D). These results established that the CNS1 region is critical for Aire mRNA and protein expression in the mouse thymus.;To determine whether the upstream CNS1 region regulates these variants, we analyzed the expression levels of the majority of exons in the Aire coding region by qPCR.Aire-KO mouse results are shown in Supporting Information Fig.2B), indicating that CNS1 is required for the thymic expression of the majority of, if not all, Aire splice variants.Deficiency of Aire protein expression was confirmed in situ by immunofluorescence staining, which showed no Aire protein in the thymi of CNS1-KO(Fig. 2D). These results established that the CNS1 region is critical for Aire mRNA and protein expression in the mouse thymus. We next analyzed the CNS1 region for its responsiveness to NF-κB stimulation in luciferase reporter assays in vitro.We inserted a CNS1 fragment containing the two NF-κB binding sites upstream of the IFN-β minimal promoter and luciferase coding region and then introduced specific mutations into the NF-κB binding sites A and B,either individually or in combination.;We next analyzed the CNS1 region for its responsiveness to NF-κB stimulation in luciferase reporter assays in vitro.We inserted a CNS1 fragment containing the two NF-κB binding sites upstream of the IFN-β minimal promoter and luciferase coding region and then introduced specific mutations into the NF-κB binding sites A and B,either individually or in combination. 26321200 chr13 83661050 83662862 Isl1 Here we show that Ldb1 is a central regulator of genome organization in cardiac progenitor cells, which is crucial for cardiac lineage differentiation and heart development. We demonstrate that Ldb1 binds to the key regulator of cardiac progenitors, Isl1, and protects it from degradation.Furthermore, the Isl1/Ldb1 complex promotes longrange enhancer-promoter interactions at the loci of the core cardiac transcription factors Mef2c and Hand2. Chromosome conformation capture followed by sequencing identified specific Ldb1-mediated interactions of the Isl1/Ldb1 responsive Mef2c anterior heart field enhancer with genes that play key roles in cardiac progenitor cell function and cardiovascular development. Importantly, the expression of these genes was downregulated upon Ldb1 depletion and Isl1/Ldb1 haplodeficiency. In conclusion,the Isl1/Ldb1 complex orchestrates a network for heart-specific transcriptional regulation and coordination in three-dimensional space during cardiogenesis. mouse epithelial Low throughput The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors 否 Heart Failure embryonic stem cell E_02_0855 3C-qPCR,3C-seq Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C). Enhancer 3C-qPCR,3C-seq -- 5430401D19Rik,9930028G15Rik,AV011172,Mef2 -- -- -- -- -- -- -- Mef2c,Mef2c,Mef2c,Mef2c,Mef2c,Mef2c,Mef2c,Mef2c,Mef2c,Mef2c,Mef2c --,--,--,--,--,--,--,--,--,--,-- Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C).;Multiple promoter-interacting elements were detected in the Mef2c lo_x0002_cus, of which some showed a lower signal in Ldb1-deficientEBs (Figure 5B). Importantly, we observed interactions of the AHF enhancer with the promoter area and with the 30 end of the Mef2c gene, which were decreased in Ldb1-deficient EBs(Figure 5B). 3C-qPCR experiments revealed a similar long-range interaction pattern in WT versus Ldb1-/-EBs during the course of cardiac differentiation and in dissected SHF and hearts of E8–10.5 embryos, confirming the 3C-seq results (Figure 5C). --;--;--;--;--;--;--;--;--;--;-- 26303528 chr8 84899088 84902859 DEK Using biochemical affinity purification, we have identified the DEK oncoprotein as a critical factor that interacts with an essential upstream enhancer element of the EKLF promoter and exerts a positive effect on EKLF levels. This element also binds a core set of erythroid transcription factors, suggesting that DEK is part of a tissue-restricted enhanceosome that contains BMP4-dependent and -independent components. Together with local enrichment of properly coded histones and an open chromatin domain, optimal transcriptional activation of the EKLF locus can be established. human connective Low throughput The DEK Oncoprotein Is a Critical Component of the EKLF/KLF1 Enhancer in Erythroid Cells 否 -- Murine erythroleukemia (MEL) line 745A,32DEpo1,293T E_02_0856 ChIP We have shown by cotransfection and in vivo analyses that the small 950-bp region adjacent to the EKLF transcription start site is sufficient for tissue-restricted expression and wished to address whether the epigenetic profile of this region supports its importance. Database perusal of modified histone H3 interactions within the critical 950-bp region of the EKLF promoter/enhancer during hematopoiesis shows that levels of the H3K4me1 active enhancer mark increase exactly in parallel with activation of EKLF expression during hematopoiesis , that is, low within the hematopoietic repopulating cells and in myeloid (CMP and MPP) progenitors but high in MEPs and erythroblasts Enhancer -- shRNA Eklf,Nan -- -- -- -- -- -- -- Klf1,Klf1,Klf1,Klf1,Klf1,Klf1 --,--,--,--,--,-- Collectively, these studies demonstrate that DEK is required for EKLF expression and directly interacts in vitro and in vivo with its cognate site in the EKLF EHS1 Enhancer.;Collectively, these studies demonstrate that DEK is required for EKLF expression and directly interacts in vitro and in vivo with its cognate site in the EKLF EHS1 Enhancer.;Collectively, these studies demonstrate that DEK is required for EKLF expression and directly interacts in vitro and in vivo with its cognate site in the EKLF EHS1 Enhancer.;Collectively, these studies demonstrate that DEK is required for EKLF expression and directly interacts in vitro and in vivo with its cognate site in the EKLF EHS1 Enhancer.;Collectively, these studies demonstrate that DEK is required for EKLF expression and directly interacts in vitro and in vivo with its cognate site in the EKLF EHS1 Enhancer.;Collectively, these studies demonstrate that DEK is required for EKLF expression and directly interacts in vitro and in vivo with its cognate site in the EKLF EHS1 Enhancer. --;--;--;--;--;-- 26300977 chr7 114541370 114542201 FOXP2 A chromosomal rearrangement in a child with severe speech and language disorder separates FOXP2 from a functional enhancer. human Low throughput A chromosomal rearrangement in a child with severe speech and language disorder separates FOXP2 from a functional enhancer 不相关 -- HEK-293,SK-N-MC E_02_0857 Luciferase Reporter Assay To test whether these regions could act as Enhancer elements we cloned them into a reporter construct in front of a minimal promoter and luciferase reporter gene.Element 1, which had multiple chromatin signatures characteristic of an enhancer, was able to act as a functional enhancer in both cell-lines (Fig. 1d).In HEK293 cells we observed a 3 fold increase of luciferase expression in comparison to the empty vector control.In SK-N-MC cells the luciferase expression increased nearly 7 fold as compared to the control. Enhancer -- Luciferase Reporter Assay CAGH44,SPCH1,TNRC10 -- -- -- -- -- -- -- FOXP2 -- To test whether these regions could act as Enhancer elements we cloned them into a reporter construct in front of a minimal promoter and luciferase reporter gene.Element 1, which had multiple chromatin signatures characteristic of an enhancer, was able to act as a functional enhancer in both cell-lines (Fig. 1d).In HEK293 cells we observed a 3 fold increase of luciferase expression in comparison to the empty vector control.In SK-N-MC cells the luciferase expression increased nearly 7 fold as compared to the control. -- 26229090 chr3 186938165 186940165 CCND1 This method detects rearrangements involving known cancer genes, including CCND1, BCL2, MYC, PDCD1LG2, NOTCH1, CIITA, and SGK1, as well as novel enhancer duplication events of likely oncogenic significance. human Low+High throughput Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in Bcell Lymphoma 相关 B-Cell Lymphoma Lymphoma Cell E_02_0858 ChIP-seq,3C,qRT-PCR This highlighted a known BCL6-interacting Enhancer region (6,16,17) 150-250 upstream of BCL6 (SE1),which overlaps the alternate breakpoint region,a recurrent site of BCL6 locus rearrangements (15). It also revealed a second Super-Enhancer overlapping the HGB-04 duplication at ?350 (SE2),and a third such region at ?500 (SE3).We used chromosome conformation capture (3C) analysis of GCB-DLBCL lymphoma cell lines (Supplementary Fig. S3A) to confirm looping of elements from super-enhancer regions to the BCL6 promoter, consistent with roles in activating this oncogene. Intriguingly, our PMBL case, HGB-04, showed a distinct acetylation pattern across these regions, with only the duplicated enhancer region, SE2, showing strong acetylation. In both cases, we detected the expected interactions between the BCL6 and MYC promoters and candidate enhancers in their native locus (Fig. 5C-D). We then used the same enhancer primers to measure interactions with the opposite gene promoter. We detected strong interactions between the MYC promoter and elements within the BCL6 SE1 and SE2 regions in HGB-07, but no such interactions in the non-rearranged tumor, HGB-06. Super-Enhancer 3C qRT-PCR BCL5A,BCL6,LAZ3,ZBTB27,ZNF51 -- -- -- RSRFR2 ChIP-Seq -- -- BCL6 MEF2B This highlighted a known BCL6-interacting Enhancer region (6,16,17) 150-250 upstream of BCL6 (SE1),which overlaps the alternate breakpoint region,a recurrent site of BCL6 locus rearrangements (15). It also revealed a second Super-Enhancer overlapping the HGB-04 duplication at ?350 (SE2),and a third such region at ?500 (SE3).We used chromosome conformation capture (3C) analysis of GCB-DLBCL lymphoma cell lines (Supplementary Fig. S3A) to confirm looping of elements from super-enhancer regions to the BCL6 promoter, consistent with roles in activating this oncogene. Intriguingly, our PMBL case, HGB-04, showed a distinct acetylation pattern across these regions, with only the duplicated enhancer region, SE2, showing strong acetylation. In both cases, we detected the expected interactions between the BCL6 and MYC promoters and candidate enhancers in their native locus (Fig. 5C-D). We then used the same enhancer primers to measure interactions with the opposite gene promoter. We detected strong interactions between the MYC promoter and elements within the BCL6 SE1 and SE2 regions in HGB-07, but no such interactions in the non-rearranged tumor, HGB-06. Rather, we observed strong, focal MEF2B binding at acetylated elements within BCL6 super-enhancer regions, including four sites in SE1, one in SE2, and two in SE3 (Fig. 3C). ChIP-Seq analysis in the Jeko-1 MCL line revealed a specific increase in H3K27ac at MEF2B binding sites in MEF2B transgene-expressing cells, but not at intervening elements within the BCL6 super-enhancers (Fig. 3E).These data support a direct role for MEF2B in the activation of enhancers that drive BCL6 expression in human lymphomas. 26214589 chr10 64737032 64737909 EGR2 EWSR1-FLI1 preferentially bound to the A risk allele,which increased global and allele-specific EGR2 expression. human Low+High throughput Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite 相关 Ewing Sarcoma embryonic stem cell E_02_0859 ChIP-seq,Luciferase Reporter Assay We observed activating chromatin marks, signals for formaldehyde-assisted isolation of regulatory elements (FAIRE) and/or DNaseI hypersensitivity at five main loci: two loci corresponding to known EGR2 regulatory elements (MSE (myelinating Schwann cell enhancer) 30 and BoneE (bone enhancer) (unpublished data); Supplementary Fig. 8), one to the ADO promoter, and two to GGAA microsatellites (mSat1 and mSat2) that overlapped with EWSR1-FLI1 ChIP-Seq signals (Fig. 3a). Luciferase reporter assays indicated that BoneE and MSE had no or weak activity in Ewing sarcoma, respectively. Enhancer -- ChIP-seq,Luciferase Reporter Assay AT591,CHN1,CMT1D,CMT4E,KROX20 -- -- -- EWS,EWS-FLI1,bK984G1.4 qRT-PCR -- -- EGR2 EWSR1 We observed activating chromatin marks, signals for formaldehyde-assisted isolation of regulatory elements (FAIRE) and/or DNaseI hypersensitivity at five main loci: two loci corresponding to known EGR2 regulatory elements (MSE (myelinating Schwann cell enhancer) 30 and BoneE (bone enhancer) (unpublished data); Supplementary Fig. 8), one to the ADO promoter, and two to GGAA microsatellites (mSat1 and mSat2) that overlapped with EWSR1-FLI1 ChIP-Seq signals (Fig. 3a). Luciferase reporter assays indicated that BoneE and MSE had no or weak activity in Ewing sarcoma, respectively. ChIP efficacy was validated by qRT-PCR using a CCND1 EWSR1-FLI1 binding site. 26214525 chr1 214150511 214151337 GATA2 We identified a putative enhancer element upstream of the key lymphatic transcriptional regulator PROX1 that is bound by GATA2, and the transcription factors FOXC2 and NFATC1. human Low+High throughput GATA2 is required for lymphatic vessel valve development and maintenance 相关 Lymphedema K-562 CELL E_02_0860 ChIP-seq,Luciferase Reporter Assay The –11 kb element was also cloned distally into the enhancer site of pGL4.12, together with a subcloned region of the Prox1 +4.5 kb element (containing GATA sites 4 and 5, see Methods for details) acting as a promoter. This addition resulted in a significant increase in luciferase activity, demonstrating that the Prox1 –11 kb element is capable of acting as an enhancer (Figure 1D). Enhancer -- Luciferase Reporter Assay PROX1 -- -- -- DCML,IMD21,MONOMAC,NFE1B,FKHL14,LD,MFH-1,MFH1,NF-ATC,NF-ATc1.2,NFAT2,NFATc ChIP -- -- PROX1,PROX1,PROX1 GATA2,FOXC2,NFATC1,GATA2,FOXC2,NFATC1,GATA2,FOXC2,NFATC1 The –11 kb element was also cloned distally into the enhancer site of pGL4.12, together with a subcloned region of the Prox1 +4.5 kb element (containing GATA sites 4 and 5, see Methods for details) acting as a promoter. This addition resulted in a significant increase in luciferase activity, demonstrating that the Prox1 –11 kb element is capable of acting as an enhancer (Figure 1D). ;The –11 kb element was also cloned distally into the enhancer site of pGL4.12, together with a subcloned region of the Prox1 +4.5 kb element (containing GATA sites 4 and 5, see Methods for details) acting as a promoter. This addition resulted in a significant increase in luciferase activity, demonstrating that the Prox1 –11 kb element is capable of acting as an enhancer (Figure 1D). ;The –11 kb element was also cloned distally into the enhancer site of pGL4.12, together with a subcloned region of the Prox1 +4.5 kb element (containing GATA sites 4 and 5, see Methods for details) acting as a promoter. This addition resulted in a significant increase in luciferase activity, demonstrating that the Prox1 –11 kb element is capable of acting as an enhancer (Figure 1D). ChIP demonstrates that GATA2, FOXC2, and NFATC1 ChIP at the PROX1 –11 kb enhancer in LECs and BECs, but not K-562 cells.;ChIP demonstrates that GATA2, FOXC2, and NFATC1 ChIP at the PROX1 –11 kb enhancer in LECs and BECs, but not K-562 cells.;ChIP demonstrates that GATA2, FOXC2, and NFATC1 ChIP at the PROX1 –11 kb enhancer in LECs and BECs, but not K-562 cells. 26211970 chr8 81286250 81293977 PAG1 To determine whether these PREs were functional, LCLs were transfected with PAG1 promoter-driven luciferase reporter constructs. PRE3 acted as a transcriptional enhancer for PAG1 exclusively when it carried the rs2370615:C allergy predisposing allele, a variant in complete linkage disequilibrium with rs7009110. human Low+High throughput Long-Range Modulation of PAG1 Expression by 8q21 Allergy Risk Variants 相关 rs7009110 National Institute of Allergy and Infectious Diseases Lymphoblastoid cell lines E_02_0861 ChIP-seq,Luciferase Reporter Assay,PCR,3C PRE2 (A) or PRE3 (B) was cloned upstream of a PAG1 promoter driven luciferase reporter with and without the candidate causal SNPs.Our 3C studies provided evidence for allele--specific chromatin looping between PRE2 and PAG1. These results demonstrate that PRE3 acts as a transcriptional enhancer in the presence of the rs2370615:C allergy predisposing allele. Enhancer 3C Luciferase Reporter Assay CBP,PAG -- -- -- CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NFKB-p105,NFKB-p50,NFkappaB,p105,p50 ChIP-seq 81291879 ChIP-seq,Luciferase Reporter Assay,3C PAG1 NFKB1 PRE2 (A) or PRE3 (B) was cloned upstream of a PAG1 promoter driven luciferase reporter with and without the candidate causal SNPs.Our 3C studies provided evidence for allele--specific chromatin looping between PRE2 and PAG1. These results demonstrate that PRE3 acts as a transcriptional enhancer in the presence of the rs2370615:C allergy predisposing allele. Based on ENCODE ChIP-seq data for LCLs,17 two transcription factors (TFs) bind to PRE3 and overlap the putative functional variant rs2370615: the RelA (or p65[MIM: 164014]) subunit of the nuclear factor (NF-)TF,which is critical for innate and adaptive immune re_x0002_sponses,22 and the POU domain class 2 transcription factor2 (POU2F2 or Oct-2 [MIM: 164176]),which regulates B-cell-specific genes. 26166704 chr21 42668000 42671000 SMC5 Together with two other such SMC-containing complexes - cohesin and SMC5/SMC6 complexes human breast Low+High throughput Condensin I and II Complexes License Full Estrogen Receptor α-Dependent Enhancer Activation -- breast cancer cell E_02_0862 ChIP-seq,ChIP,GRO-seq "Previous work from our lab and others established that a subgroup of ER-α/H3K27Ac co-bound enhancers (n=1,248,), exhibiting E2-upregulated eRNAs, high intensity of ER-α binding and close proximity to estrogen target genes, constitute the major E2-activated functional enhancers in MCF-7 cells, referred to as E2-induced ""active enhancers"" or “eRNA+ enhancers”. " Enhancer 3C ChIP-qPCR BCEI,D21S21,HP1.A,HPS2,pNR-2,pS2 -- -- -- -- -- -- -- TFF1,TFF1 --,-- Genome browser image showing the results of GRO-Seq and Pol II ChIP-Seq at TFF1 locus in the presence of condensin knockdown ( siNCAPG or siNCAPD3 ) vs siCTL transfected cell.;Genome browser image showing the results of GRO-Seq and Pol II ChIP-Seq at TFF1 locus in the presence of condensin knockdown ( siNCAPG or siNCAPD3 ) vs siCTL transfected cell. --;-- 26163528 chr12 25090158 25090663 Id2 Here, we show that Id2 promotes ileal tumor initiation in Apc-deficient mice. Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ∼80% reduction in the number of ileal polyps, but had little effect on tumor size. Notably, the lack of Id2 increased the number of apoptotic cells in the normal crypt epithelium of the mice. Furthermore, DNA microarray analysis revealed that the expression level of Max dimerization protein 1 (Mxd1), known as a c-Myc antagonist, was specifically increased by Id2 deletion in the ileal intestinal epithelium of ApcΔ716 mice. In contrast, the protein level of c-Myc, but not the mRNA level, was decreased by loss of Id2 in these mice. These results indicate that loss of Id2 inhibits tumor initiation by up-regulation of Mxd1 and down-regulation of c-Myc in ApcΔ716 mice. mouse epithelial Low throughput Id2 deletion attenuates Apc-deficient ileal tumor formation 否 Colorectal Carcinoma HCT 116,SW480 E_02_0863 Luciferase Reporter Assay,ChIP-PCR,ChIP Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ?80% reduction in the number of ileal polyps, but had little effect on tumor size. Enhancer -- Transgenic mice,RT-PCR,Western blot AI255428,C78922,Idb2,bHLHb26 -- -- -- 5730422P05Rik,ASP-I2,E2-2,E2.2,ITF-2,ITF-2b,ITF2,ME2,MITF-2A,MITF-2B,SEF-2,SEF2,SEF2-1,TFE,Tcf-4,bHLHb19 ChIP-PCR,Luciferase Reporter Assay -- -- Id2,Id2,Id2,Id2 Tcf4,Tcf4,Tcf4,Tcf4 Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ?80% reduction in the number of ileal polyps, but had little effect on tumor size.;Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ?80% reduction in the number of ileal polyps, but had little effect on tumor size.;Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ?80% reduction in the number of ileal polyps, but had little effect on tumor size.;Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ?80% reduction in the number of ileal polyps, but had little effect on tumor size. To determine if mouse Id2 is also a target gene of Wnt signaling, we performed ChIP-PCR analysis of the binding of Tcf4 to the promoter region of the Id2 gene.Sequencing analysis revealed ten putative Tcf/Lef-binding consensus sequences in the Id2 promoter region spanning from ?4000 to ?1. As expected, Tcf4 bound to the DNA region spanning from ?3300 to ?3146 of the Id2 distal promoter.To test this Tcf4 binding region for enhancer activity, we conducted luciferase reporter assays using the constructs .The putative Id2-enhancer fragment significantly activated Wnt-signaling dependent transcription from the CMV minimal promoter in two colorectal cancer cell lines.;To determine if mouse Id2 is also a target gene of Wnt signaling, we performed ChIP-PCR analysis of the binding of Tcf4 to the promoter region of the Id2 gene.Sequencing analysis revealed ten putative Tcf/Lef-binding consensus sequences in the Id2 promoter region spanning from ?4000 to ?1. As expected, Tcf4 bound to the DNA region spanning from ?3300 to ?3146 of the Id2 distal promoter.To test this Tcf4 binding region for enhancer activity, we conducted luciferase reporter assays using the constructs .The putative Id2-enhancer fragment significantly activated Wnt-signaling dependent transcription from the CMV minimal promoter in two colorectal cancer cell lines.;To determine if mouse Id2 is also a target gene of Wnt signaling, we performed ChIP-PCR analysis of the binding of Tcf4 to the promoter region of the Id2 gene.Sequencing analysis revealed ten putative Tcf/Lef-binding consensus sequences in the Id2 promoter region spanning from ?4000 to ?1. As expected, Tcf4 bound to the DNA region spanning from ?3300 to ?3146 of the Id2 distal promoter.To test this Tcf4 binding region for enhancer activity, we conducted luciferase reporter assays using the constructs .The putative Id2-enhancer fragment significantly activated Wnt-signaling dependent transcription from the CMV minimal promoter in two colorectal cancer cell lines.;To determine if mouse Id2 is also a target gene of Wnt signaling, we performed ChIP-PCR analysis of the binding of Tcf4 to the promoter region of the Id2 gene.Sequencing analysis revealed ten putative Tcf/Lef-binding consensus sequences in the Id2 promoter region spanning from ?4000 to ?1. As expected, Tcf4 bound to the DNA region spanning from ?3300 to ?3146 of the Id2 distal promoter.To test this Tcf4 binding region for enhancer activity, we conducted luciferase reporter assays using the constructs .The putative Id2-enhancer fragment significantly activated Wnt-signaling dependent transcription from the CMV minimal promoter in two colorectal cancer cell lines. 26110280 chr14 50787449 50787634 Ccnb1ip1 The Ccnb1ip1 insulator showed enhancer-blocking activity in the luciferase assays and barrier activity in the colony formation assays. Further examination of the Ccnb1ip1 locus in other mammalian species revealed that the insulator and enhancer are highly conserved among a wide variety of species, and are located immediately upstream of the transcriptional start site of Ccnb1ip1. These newly identified cis-elements may be involved in transcriptional regulation of Ccnb1ip1, which is important in meiotic crossing-over and G2/M transition of the mitotic cell cycle. mouse connective Low throughput An Insulator Element Located at the Cyclin B1 Interacting Protein 1 Gene Locus Is Highly Conserved among Mammalian Species 否 -- Cos7,NIH3T3,HeLa cell E_02_0864 Luciferase Reporter Assay,ChIP,RT-PCR PCR amplification of JF1 genomic DNA using several primer pairs targeted to differentially methylated regions identified a 1.8 kbp genomic segment that was present in the JF1 strain but absent in the B6 strain . Sequence analysis revealed that this 1.8kbp segment consisted of a 1,579 bp interval deleted in the B6 genome, and the remaining 220 bp interval present in the B6 genome but in an inverted orientation. Enhancer -- Luciferase Reporter Assay,ChIP,RT-PCR Gm288,Hei10,mei4 -- -- -- -- -- -- -- Ccnb1ip1,Ccnb1ip1,Ccnb1ip1,Ccnb1ip1,Ccnb1ip1,Ccnb1ip1 --,--,--,--,--,-- We hypothesized the existence of an insulator-type element that prevents the spreadof DNA methylation within the1.8 k segment,and actually identified a 242- and a 185- fragments that were located adjacent to eachother and showed insulatorand Enhancer activities,respectively,in reporter assays. We designated these genomicregions as the Ccnb1ip1 insulator and the Ccnb1ip1Enhancer. The Ccnb1ip1 insulator showed Enhancer-blocking activity in the Luciferaseiferase assays andbarrieractivity in the colony formation assays. Further examination of the Ccnb1ip1locus in other mammalian speciesrevealed that the insulator and Enhancerare High throughput lyconserve damonga wide variety of species,and are located immediately upstream of the transcriptional start site of Ccnb1ip1.;We hypothesized the existence of an insulator-type element that prevents the spreadof DNA methylation within the1.8 k segment,and actually identified a 242- and a 185- fragments that were located adjacent to eachother and showed insulatorand Enhancer activities,respectively,in reporter assays. We designated these genomicregions as the Ccnb1ip1 insulator and the Ccnb1ip1Enhancer. The Ccnb1ip1 insulator showed Enhancer-blocking activity in the Luciferaseiferase assays andbarrieractivity in the colony formation assays. Further examination of the Ccnb1ip1locus in other mammalian speciesrevealed that the insulator and Enhancerare High throughput lyconserve damonga wide variety of species,and are located immediately upstream of the transcriptional start site of Ccnb1ip1.;We hypothesized the existence of an insulator-type element that prevents the spreadof DNA methylation within the1.8 k segment,and actually identified a 242- and a 185- fragments that were located adjacent to eachother and showed insulatorand Enhancer activities,respectively,in reporter assays. We designated these genomicregions as the Ccnb1ip1 insulator and the Ccnb1ip1Enhancer. The Ccnb1ip1 insulator showed Enhancer-blocking activity in the Luciferaseiferase assays andbarrieractivity in the colony formation assays. Further examination of the Ccnb1ip1locus in other mammalian speciesrevealed that the insulator and Enhancerare High throughput lyconserve damonga wide variety of species,and are located immediately upstream of the transcriptional start site of Ccnb1ip1.;We hypothesized the existence of an insulator-type element that prevents the spreadof DNA methylation within the1.8 k segment,and actually identified a 242- and a 185- fragments that were located adjacent to eachother and showed insulatorand Enhancer activities,respectively,in reporter assays. We designated these genomicregions as the Ccnb1ip1 insulator and the Ccnb1ip1Enhancer. The Ccnb1ip1 insulator showed Enhancer-blocking activity in the Luciferaseiferase assays andbarrieractivity in the colony formation assays. Further examination of the Ccnb1ip1locus in other mammalian speciesrevealed that the insulator and Enhancerare High throughput lyconserve damonga wide variety of species,and are located immediately upstream of the transcriptional start site of Ccnb1ip1.;We hypothesized the existence of an insulator-type element that prevents the spreadof DNA methylation within the1.8 k segment,and actually identified a 242- and a 185- fragments that were located adjacent to eachother and showed insulatorand Enhancer activities,respectively,in reporter assays. We designated these genomicregions as the Ccnb1ip1 insulator and the Ccnb1ip1Enhancer. The Ccnb1ip1 insulator showed Enhancer-blocking activity in the Luciferaseiferase assays andbarrieractivity in the colony formation assays. Further examination of the Ccnb1ip1locus in other mammalian speciesrevealed that the insulator and Enhancerare High throughput lyconserve damonga wide variety of species,and are located immediately upstream of the transcriptional start site of Ccnb1ip1.;We hypothesized the existence of an insulator-type element that prevents the spreadof DNA methylation within the1.8 k segment,and actually identified a 242- and a 185- fragments that were located adjacent to eachother and showed insulatorand Enhancer activities,respectively,in reporter assays. We designated these genomicregions as the Ccnb1ip1 insulator and the Ccnb1ip1Enhancer. The Ccnb1ip1 insulator showed Enhancer-blocking activity in the Luciferaseiferase assays andbarrieractivity in the colony formation assays. Further examination of the Ccnb1ip1locus in other mammalian speciesrevealed that the insulator and Enhancerare High throughput lyconserve damonga wide variety of species,and are located immediately upstream of the transcriptional start site of Ccnb1ip1. --;--;--;--;--;-- 25810254 chr4 34888479 34889907 Cga Moreover, histone H3 Lys 27 (H3K27) acetylation, which was found at both enhancer and promoter in wild-type cells, appeared to have been replaced by H3K27 trimethylation at the enhancer. Thus, the Cga eRNA mediates the physical interaction between these genomic regions and determines the chromatin structure of the proximal promoter to allow gene expression. mouse connective Low throughput RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene 否 -- αT3-1 cell E_02_0865 qPCR,ChIP,3C Using quantitative PCR (qPCR) on DNase-treated reverse-transcribed RNA from a gonadotrope cell line, we amplified fragments between ?5300 and ?3872 bp upstream of the Cga TSS, which includes most of the reported enhancer. Enhancer 3C qPCR,ChIP CG-alpha,FSHA,GPHA1,GPHalpha,HCG,LHA,Tsha,aGSU,alpha-GSU,alphaGSU,alphaSU -- -- -- -- -- -- -- Cga,Cga,Cga,Cga,Cga,Cga --,--,--,--,--,-- qPCR analysis confirmed the interaction of the distal enhancer regions (?6.7 to ?6.58 and ?4.9 to ?4.85 kbp) with the proximal Cga promoter in both the treated and untreated cells and,with greater frequency, in WT and eRNA-knockdown cells after normalization to the relative levels of the Fshβ chimeric fragment;qPCR analysis confirmed the interaction of the distal enhancer regions (?6.7 to ?6.58 and ?4.9 to ?4.85 kbp) with the proximal Cga promoter in both the treated and untreated cells and,with greater frequency, in WT and eRNA-knockdown cells after normalization to the relative levels of the Fshβ chimeric fragment;qPCR analysis confirmed the interaction of the distal enhancer regions (?6.7 to ?6.58 and ?4.9 to ?4.85 kbp) with the proximal Cga promoter in both the treated and untreated cells and,with greater frequency, in WT and eRNA-knockdown cells after normalization to the relative levels of the Fshβ chimeric fragment;qPCR analysis confirmed the interaction of the distal enhancer regions (?6.7 to ?6.58 and ?4.9 to ?4.85 kbp) with the proximal Cga promoter in both the treated and untreated cells and,with greater frequency, in WT and eRNA-knockdown cells after normalization to the relative levels of the Fshβ chimeric fragment;qPCR analysis confirmed the interaction of the distal enhancer regions (?6.7 to ?6.58 and ?4.9 to ?4.85 kbp) with the proximal Cga promoter in both the treated and untreated cells and,with greater frequency, in WT and eRNA-knockdown cells after normalization to the relative levels of the Fshβ chimeric fragment;qPCR analysis confirmed the interaction of the distal enhancer regions (?6.7 to ?6.58 and ?4.9 to ?4.85 kbp) with the proximal Cga promoter in both the treated and untreated cells and,with greater frequency, in WT and eRNA-knockdown cells after normalization to the relative levels of the Fshβ chimeric fragment --;--;--;--;--;-- 25804738 chr3 127641624 127642545 Foxa1 Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons. mouse epithelial Low+High throughput Genome-wide characterisation of Foxa1 binding sites reveals several mechanisms for regulating neuronal differentiation in midbrain dopamine cells 否 -- embryonic stem cell E_02_0866 ChIP-qPCR,ChIP-seq,RNA-seq A conserved 447?bp genomic fragment within this?Neurog2?3′ Foxa1-bound peak showed enhancer activity specifically in midbrain floor plate and also in the cerebral cortex, when analysed in mouse transient transgenic experiments at E12.5 Enhancer -- Transgenic mice,qRT-PCR Atoh4,Math4A,bHLHa8,ngn-2,ngn2 -- -- -- E130306E05Rik,HNF3-beta,HNF3beta,Hnf-3b,Hnf3b,Tcf-3b,Tcf3b,Hnf-3a,Hnf3a,Tcf-3a,Tcf3a ChIP-seq,RNA-seq -- -- Neurog2,Neurog2,Neurog2,Neurog2,Neurog2,Neurog2,Neurog2,Neurog2,Neurog2 Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2,Otx2,Foxa1,Foxa2 By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors.;By contrast, the identification of a Foxa1-bound peak downstream of Neurog2 coding sequences (Neurog2 3′) raised the possibility that Foxa2 might directly activate Neurog2 expression through this putative Enhancer region in embryonic mDA progenitors. Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.;Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons. 25801169 chr1 13041306 13127367 SOX2 Our results show that ESC SEs generally consist of clusters of active enhancers that have OCT4-dependent and ESC-specific functions and demonstrate that optimal transcriptional activity of target genes is dependent on the presence of most of the constituent enhancers.Chromatin interaction data indicate that constituent enhancers physically interact within the SEs; indeed, the interactions among SE constituents in ESCs appear to be more frequent than interactions between theSE constituents and their associated gene promoters, and interactions between typical enhancers. We previously noted that enhancer clusters can be gained or lost as a unit during development or oncogenesis and have shown that large tumor SEs can collapse as a unit when depleted of the enhancer cofactor BRD4 or when a constituent is deleted. human epithelial Low throughput Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers 否 -- Embryonic Stem Cell,V6.5 and Zhbtc4 murine ESCs,C2C12,MEFs,HEK293T,HCT-116 E_02_0867 Luciferase Reporter Assay The five super-enhancers show physical interactions with their respective associated genes and are located within insulated neighborhoods in the ESC genome , suggesting that these genes represent the bona fide physiological targets of the five SEs. Super-Enhancer CRISPR/Cas9 -- Prdm14 -- -- -- 2810482H01Rik,NF-A1,Oct-1,Oct1,Otf-1,Otf1,Sox-2,lcc,ysb,2410002E02Rik,ENK,ecat4 ChIP-seq -- -- Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14,Prdm14 Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog,Oct4,Sox2,Nanog The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene;The results showed that deletion of most (12/14) super-enhancer constituents led to reduced expression of the associated gene, while in one case (Prdm14 E5) the deletion caused a small increase in expression of the associated gene ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5.;ChIP-Seq binding profiles for OCT4,SOX2 and NANOG (merged) and Mediator (MED1) at the miR-290-295 locus in ES cells.Enhancer activity measured in luciferase reporter assays in wild type cells and the change in enhancer activity after OCT4 shutdown is plotted for each constituent enhancer within the super-enhancer. The super-enhancer is depicted as a black bar above the binding profiles. The difference in values after OCT4 shutdown is statistically significant for all constituents, except from miR-290-295 M1, M3 and M5. 25786345 chr11 118767466 118769582 CXCR5 Using deletion analysis and site-directed mutagenesis of the cxcr5 gene promoter and enhancer elements, we demonstrated that p53 appears to act upon cxcr5 promoter indirectly, by repressing the activity of NFkB transcription factors. human Low throughput p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells 相关 -- MCF-7 cell E_02_0868 Luciferase Reporter Assay,PCR Genomic fragment containing cxcr5 promoter was subcloned upstream of luciferase gene in pGL3-Basic reporter vector. Another genomic fragment containing the potential cxcr5 enhancer was subcloned downstream of the luciferase gene. In order to account for lower transfection efficiency of larger plasmids, the second construct included a control genomic fragment from cxcr5 locus which was similar in length to the enhancer fragment but had no characteristic features of a regulatory sequence. Functional comparison of these two constructs in MCF-7 and MCF-7-2si cells (Figure 3A) revealed a marginal modulating effect by the enhancer (15%) towards cxcr5 promoter activity. This effect, however, was stable in both cell lines, indicating that activity of the cxcr5 intronic enhancer in breast cancer cells was independent of the p53 status. Enhancer -- Luciferase Reporter Assay,PCR BLR1,CD185,MDR15 -- -- -- NEDCPMD,NF,NRCAML ChIP,PCR -- -- CXCR5 NFASC Genomic fragment containing cxcr5 promoter was subcloned upstream of luciferase gene in pGL3-Basic reporter vector. Another genomic fragment containing the potential cxcr5 enhancer was subcloned downstream of the luciferase gene. In order to account for lower transfection efficiency of larger plasmids, the second construct included a control genomic fragment from cxcr5 locus which was similar in length to the enhancer fragment but had no characteristic features of a regulatory sequence. Functional comparison of these two constructs in MCF-7 and MCF-7-2si cells (Figure 3A) revealed a marginal modulating effect by the enhancer (15%) towards cxcr5 promoter activity. This effect, however, was stable in both cell lines, indicating that activity of the cxcr5 intronic enhancer in breast cancer cells was independent of the p53 status. Map of cxcr5 promoter,predicted NF -binding sites and PCR products amplified in ChIP assay. 25782671 chr7 155845627 155847652 SHH Most of these malformations are due to the gain-of-function of the Zone of Polarizing Activity Regulatory Sequence, the only limb-specific enhancer of SHH known to date. human Low throughput The disruption of a novel limb cis-regulatory element of SHH is associated with autosomal dominant preaxial polydactyly-hypertrichosis 相关 -- Caco-2 cell E_02_0869 Luciferase Reporter Assay The 2026 bp sequence was subcloned into the expression vector pLS_Prom_SHH. As the human colon adenocarcinoma Caco2 cell line expresses SHH,we therefore performed transfections in these cells with the construct containing the 2026 bp sequence in forward (pLS_Prom_SHH_2026F) and reverse orientation (pLS_Prom_SHH_2026R). Both constructs show an approximately twofold decrease of the relative reporter activity, as compared with the control vector without regulatory element pLS_Prom_SHH (Figure 4). Thus, the 2026 bp sequence contains an element capable of repressing the transcriptional activity of the SHH promoter in cis, consistent with a silencer activity. Enhancer -- Luciferase Reporter Assay HHG1,HLP3,HPE3,MCOPCB5,SMMCI,ShhNC,TPT,TPTPS -- -- -- -- -- -- -- SHH -- The 2026 bp sequence was subcloned into the expression vector pLS_Prom_SHH. As the human colon adenocarcinoma Caco2 cell line expresses SHH,we therefore performed transfections in these cells with the construct containing the 2026 bp sequence in forward (pLS_Prom_SHH_2026F) and reverse orientation (pLS_Prom_SHH_2026R). Both constructs show an approximately twofold decrease of the relative reporter activity, as compared with the control vector without regulatory element pLS_Prom_SHH (Figure 4). Thus, the 2026 bp sequence contains an element capable of repressing the transcriptional activity of the SHH promoter in cis, consistent with a silencer activity. -- 25775043 chr17 35499359 35507923 Tbx3 This previously unannotated ESC-specific enhancer is positioned ~10 kb upstream of transcription factor–encoding Tbx3, a gene previously implicated in the maintenance of pluripotency20.We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression. Indeed, we detected a relative reduction of Tbx3 mRNA and protein expression upon targeting Enh1 with dCas9-LSD1. mouse connective Low throughput Functional annotation of native enhancers with a Cas9–histone demethylase fusion 否 -- embryonic stem cell E_02_0870 CRISPR/Cas9,3C,Luciferase Reporter Assay,ATAC-seq We generated mouse embryonic stem cells (mESCs) expressing versions of Neisseria meningitidis (Nm) dCas9 fused with LSD1, a non-effector BirA affinity tag (BAT), or a KRAB repressor and used a viral delivery system for sgRNAs. We first targeted the well-characterized cis-regulatory region of Oct417, a factor critical for the ESC state. Oct4 expression is regulated by a proximal enhancer (OPE) active in epiblast cells, and a distal enhancer (ODE) active in mESCs and cells of the inner cell mass. Targeting of LSD1 to the ODE resulted in loss of Oct4 expression and appearance of OCT4-negative colonies accompanied by phenotypic changes compared to control dCas9-BAT cells targeted to the same enhancer. Enhancer 3C,CRISPR/Cas9 PCR,ChIP NF-A3,Oct-3,Oct-3/4,Oct-4,Oct3,Oct3/4,?Oct4,Otf-3,Otf-4,Otf3,Otf3-rs7,Otf3g,Otf4 We conclude that the dCas9-LSD1 fusion protein allows for an effector dependent definition of functional, native enhancer elements that help to maintain a given cellular state. 3C We conclude that the dCas9-LSD1 fusion protein allows for an effector dependent definition of functional,native Enhancer elements that help to maintain a given cellular state.Accordingly,dCas9-LSD1 provides a rapid and powerful approach to understanding distal cis-regulatory regions such as Enhancers without major disruption of the local genomic architecture. D5Ertd189e PCR,Luciferase Reporter Assay,ChIP,3C -- -- Oct-4,Oct-4,Oct-4,Oct-4,Oct-4,Oct-4,Oct-4 Tbx3,Tbx3,Tbx3,Tbx3,Tbx3,Tbx3,Tbx3 For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence..;For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence..;For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence..;For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence..;For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence..;For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence..;For follow-up, we focused on the putative Enhancer with the highest differential score,Enh1.Test of Enh1 in a reporter assay confirmed its ability to enhance expression at comparable levels to an Oct4 DE sequence.. This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression.;This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression.;This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression.;This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression.;This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression.;This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression.;This previously unannotated ESC_x0002_specific Enhancer is positioned ~10kb upstream of the transcription factor Tbx3, a gene previously implicated in the maintenance of pluripotency20. We therefore hypothesized that Enh1 may function in the ESC network by regulating Tbx3 expression. 25704602 chr10 123099588 123100426 FGFR2 The second, a non-coding mutation, disrupted the activity of a neural crest enhancer downstream of FGFR2 both in vitro and in vivo. human Low throughput Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci 相关 Cleft Palate GMSM-K E_02_0871 Luciferase Reporter Assay,PCR The same FGFR2 +254 construct used in the zebra?sh studies (GRCh37, chr10: 123,099,588–123,100,426) was modi?ed by PCR-mediated mutagenesis to test the de novo mutation at GRCh37, chr10: 123,099,960. In transient transgenic reporter studies in zebra?sh embryos, we demonstrated that the reference allele of the human +254 kb element has enhancer activity in the neural keel (Figure 3C), brain (Figure 3D), and delaminating neural crest (Figure S18), consistent with expression of Fgfr2 in brain and cranial neural folds in mice and zebra?sh.In parallel experiments, the de novo mutation revealed enhancer activity in fewer embryos (3/83) than the reference allele (41/82; p ? 1.70 3 10 12 )(Figures 3E and S18). Enhancer -- Luciferase Reporter Assay,PCR BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25 -- -- -- -- -- -- -- FGFR2 -- The same FGFR2 +254 construct used in the zebra?sh studies (GRCh37, chr10: 123,099,588–123,100,426) was modi?ed by PCR-mediated mutagenesis to test the de novo mutation at GRCh37, chr10: 123,099,960. In transient transgenic reporter studies in zebra?sh embryos, we demonstrated that the reference allele of the human +254 kb element has enhancer activity in the neural keel (Figure 3C), brain (Figure 3D), and delaminating neural crest (Figure S18), consistent with expression of Fgfr2 in brain and cranial neural folds in mice and zebra?sh.In parallel experiments, the de novo mutation revealed enhancer activity in fewer embryos (3/83) than the reference allele (41/82; p ? 1.70 3 10 12 )(Figures 3E and S18). -- 25701871 chr5 125345378 125345495 LMNB1 Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. human Brain Low throughput A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) 相关 Adult-onset Autosomal Dominant Demyelinating Leukodystrophy HIT DH5A cell (RBC) E_02_0872 Luciferase Reporter Assay,4C,PCR To test the predicted enhancers experimentally, we perfor-ed dual-luciferase reporter assays with constructs containing regions A, B, C or D, in direct or reverse orientation, upstream of the LMNB1 promoter . Following transfection of the constructs into HEK293T human cell line, regions A and B (in both orientations) signi?cantly increased luciferase expression (A forward = 1.97 ± 0.2; A reverse = 1.8 ± 1.6; B forward = 2.52 ± 0.25; B reverse = 1.85 ± 0.10; mean ± standard error; P < 0.01; Fig. 3C). In contrast, constructs containing regions C and D did not signi?cantly affect luciferase expression (Fig. 3C). Similar results were obtained when the same plasmids were transfected into NIH3T3 cell line (data not shown), suggesting that the enhancer activity of regions A and B could function across species, at least in mouse ?broblasts. Following these results, regions A and B were subsequently referred to as enhancer region A (Enh-A) and enhancer region B (Enh-B). Enhancer 4C Luciferase Reporter Assay,PCR ADLD,LMN,LMN2,LMNB -- -- -- -- -- -- -- LMNB1 -- To test the predicted enhancers experimentally, we perfor-ed dual-luciferase reporter assays with constructs containing regions A, B, C or D, in direct or reverse orientation, upstream of the LMNB1 promoter . Following transfection of the constructs into HEK293T human cell line, regions A and B (in both orientations) signi?cantly increased luciferase expression (A forward = 1.97 ± 0.2; A reverse = 1.8 ± 1.6; B forward = 2.52 ± 0.25; B reverse = 1.85 ± 0.10; mean ± standard error; P < 0.01; Fig. 3C). In contrast, constructs containing regions C and D did not signi?cantly affect luciferase expression (Fig. 3C). Similar results were obtained when the same plasmids were transfected into NIH3T3 cell line (data not shown), suggesting that the enhancer activity of regions A and B could function across species, at least in mouse ?broblasts. Following these results, regions A and B were subsequently referred to as enhancer region A (Enh-A) and enhancer region B (Enh-B). -- 25652130 chr4 135548688 135550688 Cdh1 We show that Cdh1 activity during MET is governed by two enhancers at +7.8 kb and at +11.5 kb within intron 2 that are activated by binding of Grhl3 and Hnf4α, respectively. Recruitment of Grhl3 and Hnf4α to the enhancers is crucial for activating Cdh1 and accomplishing MET in non-tumorigenic mouse mammary gland cells (NMuMG). Moreover, the two enhancers cooperate via Grhl3 and Hnf4α binding, induction of DNA-looping and clustering at the promoter to orchestrate E-cadherin re-expression. Our results provide novel insights into the cellular mechanisms whereby cells respond to MET signals and re-establish an epithelial phenotype by enhancer cooperativity. mouse epithelial Low throughput Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition 否 -- NMuMG,Hepa1–6,CMT,HEK-293 E_02_0873 Luciferase Reporter Assay,3C We reported previously that intron 2 of Cdh1 is essential for proper E-cad expression.In order to analyze this large DNA sequence(>40 kb) for putative enhancers we focused on evolutionary conserved sequences. Enhancer 3C ChIP,qPCR AI561912,Get1,Som,Tfcp2l4,ct -- -- -- -- -- -- -- Grhl3,Grhl3,Grhl3,Grhl3 --,--,--,-- Weshow thatCdh1 activity during MET isgovernedby 33 two Enhancers at +7.8 and at +11.5 within intron 2 that are activated by binding of Grhl3 and Hnf4α, 34 respectively.;Weshow thatCdh1 activity during MET isgovernedby 33 two Enhancers at +7.8 and at +11.5 within intron 2 that are activated by binding of Grhl3 and Hnf4α, 34 respectively.;Weshow thatCdh1 activity during MET isgovernedby 33 two Enhancers at +7.8 and at +11.5 within intron 2 that are activated by binding of Grhl3 and Hnf4α, 34 respectively.;Weshow thatCdh1 activity during MET isgovernedby 33 two Enhancers at +7.8 and at +11.5 within intron 2 that are activated by binding of Grhl3 and Hnf4α, 34 respectively. --;--;--;-- 25651906 chr7 46351197 46355693 Wnt3a In the present study, we tested the regulation of MyoD cis-regulatory elements by Wnt3a secreted from human embryonic kidney (HEK)-293T cells. We found that Wnt3a activated the MyoD proximal 6.0k promoter (P6P) only marginally, but highly enhanced the activity of the composite P6P plus distal enhancer (DE) reporter through canonical and non-canonical pathways. Further screening of the intervening fragments between the DE and the P6P identified a strong Wnt-response element (WRE) in the upstream -8 to -9k region (L fragment) that acted independently of the DE, but was dependent on the P6P. Deletion of a Pax3/Pax7-targeted site in the L fragment significantly reduced its response to Wnt3a, implying that Wnt3a activates the L fragment partially through Pax3/Pax7 action. Binding of β-catenin and Pax7 to their target sites in the DE and the L fragment respectively was also demonstrated by ChIP. mouse muscle Low throughput Wnt3a signal pathways activate MyoD expression by targeting cis-elements inside and outside its distal enhancer 否 -- C2C12,HEK-293T E_02_0874 Luciferase Reporter Assay,ChIP C2C12 myoblasts stably carrying the P6P (?5870 to +95) -driven reporter (MyoD-P6P-luc) or another composite reporter,MyoD-PE-luc, containing P6P plus the DE (?25277 to?20780) were treated with Wnt3a medium. We found that Wnt3a marginally, but significantly, activated MyoDP6P-luc activity; however, Wnt3a strongly activated MyoD-PE-luc, suggesting that one or multiple Wnt-response elements(WREs) are located within the DE. Enhancer -- Western blot,qRT-PCR AI503393,MYF3,MyoD,?Myod-1,bHLHc1 -- -- -- Wnt-3a,vt Luciferase Reporter Assay -- -- Myod1,Myod1,Myod1,Myod1,Myod1,Myod1,Myod1,Myod1,Myod1,Myod1,Myod1,Myod1 Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a,Wnt3a A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD.;A distal Enhancer(DE) centred at ? 20 kb, when combined with a ? 2.5k proximal pro_x0002_moter, can also recapitulate human MyoD expression in vivo,demonstrating its critical role in determining the spatiotemporal expression of human MyoD. Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment.;Serial deletion mutants of DE region were generated later to identify the minimal WRE,and we found that a region of 3 kb (fragment 10, ?24 to ?21 kb)in DE was required to retain the full Wnt3a response.Deletion of sequence at either the 5_x0002_ end (fragment 8) or the 3_x0002_ end(fragment 7) significantly reduced its Wnt3a response, comparedwith fragment. 25644605 chr8 83287848 83288068 PRDM16 PR domain-containing 16 (PRDM16) induces expression of brown fat-specific genes in brown and beige adipocytes,although the underlying transcription-related mechanisms remain largely unknown. human Brown adipose Low throughput PRDM16 enhances nuclear receptor_x005f_x0002_dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1 否 -- brown fat cell E_02_0875 ChIP,RT-PCR we hypothesized that PRDM16 might be recruited to the enhancer region of the Ucp1 gene through the interaction with PGC-1a. This possibility was tested in an immobilized template assay with purified proteins and a beadimmobilized DNA fragment spanning the 220-bp Ucp1 enhancer. Enhancer -- ChIP,RT-PCR AI385626,Slc25a7,Ucp -- -- -- 5730557K01Rik,csp1,mel1 ChIP -- -- Ucp1 Prdm16 Overall, these results indicate that the ZF1 domain is required for the recruitment of PRDM16 to the Ucp1 enhancer through MED1 and PGC-1a. To determine whether PRDM16 is recruited to the Enhancer following Ucp1 induction, we treated Med1 +/+MEFs that stably express PPARg and PRDM16 with forskolin and performed a chromatin immunoprecipitation (ChIP) assay with an antibody specific for PRDM16. 25628225 chr17 6285838 6586838 SLC13A5 Utilizing cell-based luciferase reporter assays, electro_x0002_phoretic mobility shift assays, and chromatin immunoprecipitation assays, we identified and functionally characterized two enhancer modules located upstream of the SLC13A5 gene transcription start site that are associated with regulation of PXR-mediated SLC13A5 induction. human Liver Low throughput SLC13A5 Is a Novel Transcriptional Target of the Pregnane X Receptor and Sensitizes Drug-Induced Steatosis in Human Liver 不相关 Steatosis hepatocyte E_02_0876 Luciferase Reporter Assay,EMSA,ChIP Utilizing cell-based Luciferaseassays,electrophoretic mobility shift assays,and Chromatin immunoprecipitation assays,we identified and functionally characterized two Enhancer modules located upstream of the SLC13A5 gene transcription start site that are associated with regulation of PXR-mediated SLC13A5 induction. Enhancer -- Luciferase Reporter Assay,EMSA,ChIP EIEE25,INDY,NACT,mIndy -- -- -- BXR,ONR1,PAR,PAR1,PAR2,PARq,PRR,PXR,SAR,SXR EMSA -- -- SLC13A5 NR1I2 Utilizing cell-based Luciferaseassays,electrophoretic mobility shift assays,and Chromatin immunoprecipitation assays,we identified and functionally characterized two Enhancer modules located upstream of the SLC13A5 gene transcription start site that are associated with regulation of PXR-mediated SLC13A5 induction. Utilizing in vitro EMSA,we found that heterodimer of PXR and the retinoid X receptor binds specifically to DR4-1 and DR4-2 at intensities equal to or exceeding that of the everted-repeat (ER6) element from CYP3A4 promoter. 25622893 chr17 61927353 61928827 Tcam1 At the mouse locus, a multifunctional dual promoter–enhancer (DPE) controls the expression of Tcam1 and Smarcd2 genes. mouse Low throughput Characterization of the human TCAM1P pseudogene and its activation by a potential dual promoter–enhancer: Comparison with a protein-coding mouse orthologue 不相关 -- GC-spd(ts),Hepa 1-6,293T E_02_0877 PCR,Luciferase Reporter Assay We first investigated enhancer activity of hCNS1. Because TSS of TCAM1P--I and TCAM1P--III was +401 and three TSSs of TCAM1P--II were close to +401 (Fig. 2E), we cloned about 2--kb sequence upstream of +401 as a major promoter of the TCAM1P gene and connected it to the luciferase gene (TCAM1P--Pro--luc). hCNS1 was amplified by genome PCR and cloned to upstream of the TCAM1P promoter (hCNS1--Pro--luc) or to downstream of the luciferase gene(Pro--luc--hCNS1 and Pro--luc--rev hCNS1).The activity of hCNS1--Pro--luc was significantly increased in all three cell lines compared to the construct without hCNS1 (Fig. 3A). Enhancer -- Luciferase Reporter Assay TCAM1 -- -- -- -- -- -- -- TCAM1P,TCAM1P --,-- We also examined the luciferase activity in linearized constructs. If hCNS1 was actually a DPE, it might drive the transcription of the entire sequence in a circular plasmid, which might affect the luciferase gene expression.To prevent hCNS1 from driving the luciferase gene transcription in the sense direction, we linearized Pro--luc--hCNS1 and Pro--luc--rev hCNS1 constructs by cutting the immediate downstream sequence of hCNS1 and rev hCNS1. As a result, hCNS1 still significantly increased TCAM1P promoter activity in HEK293T cells, and the fold--increases were around 3 in both constructs compared to the linearized TCAM1P--Pro--luc construct (Fig. 3B). These data showed that hCNS1 could function as an enhancer for the TCAM1P gene.;We also examined the luciferase activity in linearized constructs. If hCNS1 was actually a DPE, it might drive the transcription of the entire sequence in a circular plasmid, which might affect the luciferase gene expression.To prevent hCNS1 from driving the luciferase gene transcription in the sense direction, we linearized Pro--luc--hCNS1 and Pro--luc--rev hCNS1 constructs by cutting the immediate downstream sequence of hCNS1 and rev hCNS1. As a result, hCNS1 still significantly increased TCAM1P promoter activity in HEK293T cells, and the fold--increases were around 3 in both constructs compared to the linearized TCAM1P--Pro--luc construct (Fig. 3B). These data showed that hCNS1 could function as an enhancer for the TCAM1P gene. --;-- 25605944 chr12 3944001 3947078 LDB1 Recently, using an engineered transcription unit as a model, LIM domain-binding protein 1 (LDB1) has been reported to be capable of mediating promoter:enhancer looping through LDB1 homodimerization human Low+High throughput Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program 否 -- AtT-20,Pituitary Corticotrope Cell E_02_0878 ChIP-seq,3C,ChIP Further, we have defined the subset of the enhancers that have active chromatin markers (H3K27ac and p300).Motif enrichment analysis of H3K27ac+ p300+ enhancers revealed enrichment of binding sites for the CCCTC-binding factor (CTCF), neurofibromin 1 (NF1), bHLH, FORKHEAD, X-BOX,and T-BOX families of transcription factors. Although members of the CTCF and NF1 family are general cellular transcription factors, the factors in the bHLH and other families may be critical for lineage development and enhancer programming in corticotropes. Enhancer 3C,CRISPR/Cas9 qPCR,ChIP,GRO-seq ACTH,BE,Beta-LPH,Clip,Gamma-LPH,Npp-1,Pomc1,alpha-MSH,alphaMSH,beta-MSH,gamma-MSH,?Pomc LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target genes qPCR,3C,GRO-seq Together,our data reveal that Enhancer-bound LDB1 has a role in mediating the actions of both activating and repressive Enhancers in a cell type_x0002_specific gene-regulation program. -- -- -- -- Pomc -- We found that enhancer:promoter interactions between LDB1-bound enhancers and the adjacent promoters of POMC and lung carcinoma myc related oncogene 1 (Lmyc1) genes were greatly diminished following knockdown of Ldb1. -- 25604083 chr17 69487560 69491400 SOX9 An SRY-dependent testis-specific enhancer for Sox9 has been identified only in mice. human Somatic Low throughput Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development 相关 Disorders Of Sexual Development HEK-293 cells E_02_0879 Luciferase Reporter Assay,Transgenic mice Finally, we performed transfections of reporter gene constructs under control of the minimal Sox9 promoter and additional XYSR fragments into various cell lines.For this, the 32.5 kb region was subdivided into 17 overlapping fragments,F1 to F17 (?gure 3). Whereas none of the conserved elements CNE1–7 showed Sertoli cell-speci?c activity (not shown),of all 24 constructs tested, F8 showed the highest luciferase activities in both Sertoli-like cell lines (see online supplementary ?gure S5A, B).In contrast, the same fragment had little in?uence on luciferase activity in both HEK293 and neuro-2a control cell lines (see online supplementary ?gure S5C, D). Even though F7 and F9 overlap with F8 (?gure 3 and online supplementary ?gure S6), their luciferase activities are weak in TM-4 and unremarkable in NT2/D1. Thus F8 appeared to be the best candidate for a testis-speci?c enhancer of the SOX9 gene. Enhancer -- Luciferase Reporter Assay,Transgenic mice CMD1,CMPD1,SRA1,SRXX2,SRXY10 -- -- -- BBP, D11S636, MBBP, ZCCHC25, ZFM1, ZNF162,AWT1, GUD, NPHS4, WAGR, WIT-2, WT33 Luciferase Reporter Assay -- -- SOX9 SF1,WT1 Finally, we performed transfections of reporter gene constructs under control of the minimal Sox9 promoter and additional XYSR fragments into various cell lines.For this, the 32.5 kb region was subdivided into 17 overlapping fragments,F1 to F17 (?gure 3). Whereas none of the conserved elements CNE1–7 showed Sertoli cell-speci?c activity (not shown),of all 24 constructs tested, F8 showed the highest luciferase activities in both Sertoli-like cell lines (see online supplementary ?gure S5A, B).In contrast, the same fragment had little in?uence on luciferase activity in both HEK293 and neuro-2a control cell lines (see online supplementary ?gure S5C, D). Even though F7 and F9 overlap with F8 (?gure 3 and online supplementary ?gure S6), their luciferase activities are weak in TM-4 and unremarkable in NT2/D1. Thus F8 appeared to be the best candidate for a testis-speci?c enhancer of the SOX9 gene. Such an enhancer should be under control of SRY, but could possibly also be in?uenced in its activity by other transcription factors present in the early gonad and essential for gonadal differentiation, including SF1 (also known as NR5A1), WT1, and GATA4. To test this assumption, a luciferase reporter containing F8 in front of the ?-globin TATA box was co-transfected in neuro-2a cells with expression plasmids for these factors. Of all factors tested, only SRY elicited a substantial 10-fold increase in luciferase activity. WT1 stimulated reporter activity two fold, whereas SF1 and GATA4 were completely ineffective (?gure 4A). 25582196 chr10 62893206 62923461 Tet1 New transgenic reporters using Tet1 and Tet2 cis-regulatory domains may serve to distinguish nuanced changes in pluripotent states and the underlying epigenetic variations. mouse Embryonic Low+High throughput Dynamic switching of active promoter and enhancer domains regulates Tet1 and Tet2 expression during cell state transitions between pluripotency and differentiation 否 -- embryonic stem cell E_02_0880 ChIP-seq,Luciferase Reporter Assay To identify cis-regulatory elements in Tet1, we surveyed its epigenome in mouse ESCs using ChIP-seq data sets.The combinatorial binding profiles of pluripotency factors, Mediator,and cohesin units have previously delineated a superenhancer domain in Tet1, a 15.2-kb region that spans from exon 1c at the distal end to a conserved noncoding sequence (CNS) upstream of the CDS ChIP-seq showed strong binding profiles of Oct4 within the CNS,as previously shown, but also several more strong peaks in the distal region between exons 1b and 1c. Super-Enhancer -- PCR,EMSA 2510010B09Rik,AA517754,BB001228,Cxxc6,D10Ertd17e,LCX,mKIAA1676 -- -- -- 2810482H01Rik,NF-A1,Oct-1,Oct1,Otf-1,Otf1,Sox-2,lcc,ysb EMSA -- -- Tet1,Tet1 Oct4,Sox2,Oct4,Sox2 Here we defined the promoter and Enhancer domains in Tet1 and Tet2.Within a 15- “superEnhancer” of Tet1,there are two transcription start sites (TSSs) with different activation patterns during development.;Here we defined the promoter and Enhancer domains in Tet1 and Tet2.Within a 15- “superEnhancer” of Tet1,there are two transcription start sites (TSSs) with different activation patterns during development. Contribution of Oct and Sox motifs in Tet1 and Tet2 enhancer fragments.;Contribution of Oct and Sox motifs in Tet1 and Tet2 enhancer fragments. 25505291 chr1 23881244 23881761 Id3 Analysis of Id3 regulatory sequences revealed a novel enhancer, located between +4517 and 4662 bp, but the luciferase reporter assay demonstrated that this enhancer is not Smad2/3 dependent. mouse Low throughput TGF-b1, but Not Bone Morphogenetic Proteins, Activates Smad1/5 Pathway in Primary Human Macrophages and Induces Expression of Proatherogenic Genes 不相关 Cardiometabolic Disorders Human Monocytes/Macrophages E_02_0881 Luciferase Reporter Assay Using ECR browser (http://ecrbrowser.dcode.org/), we found two conserved regions,ECR1 located between -3177 and -2660 bp upstream of transcription start and ECR2 located between +4517 and 4662 bp downstream of the gene (sequences provided in Supplemental Table 1). ECR1 overlaps with the enhancer described by Shepherd et al. (32), whereas ECR2 has not been described to date. To test the impact of identi?ed ECRs on the regulation of Id3 expression, we cloned them into a pGL3basic vector together with about a 1-kb fragment of the Id3 promoter (Fig. 1A). Obtained plasmids were transfected using nucleofection into primary monocyte-derived macrophages cultivated in the presence of IL-4 and dexamethasone for 6 d. Cells after transfection were further cultivated for 24 h and then stimulated with TGF- 1forthenext 24 h. Cells were harvested and luciferase activity was measured. Without TGF- 1 stimulation, all reporter constructs showed low promoter activity. Stimulation of macrophages with TGF- 1ledto a 2-fold upregulation of the promoter activity. Addition of ECR1 or ECR2 led to a 5-fold increase of promoter activity. Reporter plasmid containing both of them showed nearly 12-fold upregulation of promoter activity, indicating that ECRs have an additive effect (Fig. 1B). Enhancer -- Luciferase Reporter Assay HEIR-1,bHLHb25 -- -- -- -- -- -- -- ID3 -- To test the impact of identi?ed ECRs on the regulation of Id3 expression, we cloned them into a pGL3basic vector together with about a 1-kb fragment of the Id3 promoter (Fig. 1A). Obtained plasmids were transfected using nucleofection into primary monocyte-derived macrophages cultivated in the presence of IL-4 and dexamethasone for 6 d. Cells after transfection were further cultivated for 24 h and then stimulated with TGF- 1forthenext 24 h. Cells were harvested and luciferase activity was measured. Without TGF- 1 stimulation, all reporter constructs showed low promoter activity. Stimulation of macrophages with TGF- 1ledto a 2-fold upregulation of the promoter activity. Addition of ECR1 or ECR2 led to a 5-fold increase of promoter activity. Reporter plasmid containing both of them showed nearly 12-fold upregulation of promoter activity, indicating that ECRs have an additive effect (Fig. 1B). -- 25486255 chr3 34743178 34776096 Sox2 The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. mouse Brain Low+High throughput CRISPR Reveals a Distal Super-Enhancer Required for Sox2 Expression in Mouse Embryonic Stem Cells 否 -- embryonic stem cell E_02_0882 ChIP-seq,RNA-seq We examined ENCODE ChIP-seq data from 23 different mouse tissues or cell types focusing on the Sox2 locus. Using H3K27ac, a histone mark for active enhancers, we observed a distal SE that is only present in mouse ESC lines, which is approximately 100kb downstream from the Sox2 locus. This sequence spans a relatively large 13kb region, and corresponds to a recently defined super-enhancer or stretch enhancer. Super-Enhancer CRISPR/Cas9 PCR Sox-2,lcc,ysb SE is occupied by Oct4, Sox2, Nanog,and the mediator complex, and physically interacts with the Sox2 locus via DNA looping RT-qPCR,ChIP-seq To test the in vivo function of Sox2-SEdistal, we sought to delete the entire Enhancer sequence from the endogenous locus. Given that the SE spans a,13kb region, deletion of this region using conventional methods would be very inefficient.Therefore, we explored whether the recently developed CRISPR technology could be utilized to delete this large non-coding sequence in mouse ESCs. 2810482H01Rik,NF-A1,Oct-1,Oct1,Otf-1,Otf1,Sox-2,lcc,ysb,2410002E02Rik,ENK,ecat4 ChIP-seq -- -- Sox2 Oct4,Sox2,Nanog We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-Enhancer (SE) located 100kb downstream of Sox2 in mouse ESCs. First, we observed strong H3K27ac signal at this SE in two additional mouse ES cell lines (F123 and J1), indicating that usage of this SE is conserved across different mice strains.Previously published ChIP-seq data shows that Sox2-SEdistal is occupied by Oct4,Sox2 and Nanog. 25486239 chr1 133303739 133325138 Kiss1 Taken together, the present results indicate that 5-upstream region of Kiss1 locus plays a critical role in Kiss1 gene expression in an ARC-specific manner and that the recruitment of estrogen receptor- and formation of a chromatin loop between the Kiss1 promoter and the 5 enhancer region may be required for the induction of ARC-specific Kiss1 gene expression. mouse ARC and AVPV Low+High throughput Identification of Hypothalamic Arcuate Nucleus_x005f_x0002_Specific Enhancer Region of Kiss1 Gene in Mice 否 -- Kisspeptin-Immunoreactive Cell E_02_0883 DNase-seq,Immunofluorescence,Luciferase Reporter Assay,PCR,3C Using open Chromatin mapping by DNase-seq in HTE cell,the core of DHS-44 was localized to 600 at hg 19,Chr7:117075400-117076000.This region was marked by enrichment of H3K27Ac in 16HBE14o-cell,consistent with DHS-44 encompassing an active Enhancer element. Enhancer 3C Transgenic mice kisspeptin,metastatin The 5'-upstream region of Kiss1 locus functions as an enhancer for ARC Kiss1 gene expression in mice. 3C In addition,the current 3C and ER ChIP assays suggest that the Chromatin loop formation between the ARC-specific Enhancer and the promoter region of Kiss1 gene and unoccupied ER recruitment to the putative Enhancer region are involved in Kiss1 gene expression in the ARC 2610524P08Rik,9130407C09Rik,AU019798,Era,M-ERA,MERA-S,MERA-W ChIP -- -- Kiss1 Eral1 The present study aimed to determine ARC-specific enhancer(s) of the Kiss1 gene by an in vivo reporter assay.The 3C assay was performed to detect interactions between the Kiss1 promoter region and the 5 -upstream region, the latter of which was identified as an ARCspecific enhancer in the present study The binding of ERa in the 5' upstream region (Figure 4) was determined by a ChIP assay with ERa antibody. 25453903 chr14 97410723 97443618 VRK1 These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators, while activating oncogenes and new potential therapeutic targets, such as the kinase VRK1. human bone Low+High throughput EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma Ewing Sarcoma HeLa,T cell E_02_0884 shRNA,RNA-seq,qRT-PCR,3C,Immunohistochemistry Finally, we sought to address the impact of altered cis-regulatory element activity on the transcriptional landscape of Ewing sarcoma. We performed RNA sequencing (RNA-seq) in the Ewing sarcoma lines before and after EWS-FLI1 knock-down. By mapping EWS-FLI1 distal elements to the nearest expressed genes, we observed a strong relationship between changes in enhancer activity and changes in proximal gene expression (p < 10?10). We confirmed a subset of regulated gene targets by qRT-PCR. We hypothesized that direct regulatory targets of EWS-FLI1 might represent attractive therapeutic targets in Ewing sarcoma and thus ranked target genes by combined changes in chromatin and expression (Fig. 5B). Another top candidate is VRK1, a cell cycle dependent tyrosine kinase involved in G2-M transition (Valbuena et al., 2011). VRK1 is proximal to an EWS-FLI1 dependent enhancer that is active in Ewing sarcoma cell lines and primary tumors and induced de novo by the fusion protein in MSCs (Fig. 5C). Chromatin conformation studies (3C) confirmed the long distance interaction between the EWS-FLI1-bound enhancer and the VRK1 promoter in both SKNMC and A673 cells (Fig. 5D and E, respectively). Enhancer 3C Immunohistochemistry,shRNA PCH1,PCH1A -- -- -- EWS, EWS-FLI1, bK984G1.4，EWSR1 qRT-PCR,3C,shRNA -- -- VRK1 EWSR1 VRK1 is proximal to an EWS-FLI1 dependent Enhancer that is active in Ewing sarcoma cell lines and primary tumors and induced de novo by the fusion protein in MSCs Chromatin conformation studies (3C) confirmed the long distance interaction between the EWS-FLI1-bound enhancer and the VRK1 promoter in both SKNMC and A673 cells (Fig. 5D and E, respectively). VRK1 protein expression was confirmed in 15/15 primary Ewing sarcoma samples analyzed by immunohistochemistry, which revealed strong VRK1 signals in virtually all cells (Fig.6A and Fig. S5B). EWS-FLI1 knock-down markedly reduced VRK1 expression in the cell lines, while EWS-FLI1 induction was sufficient to up-regulate this kinase in MSCs (Fig. 6B and S5C). We performed RNA sequencing (RNA-seq) in the Ewing sarcoma lines before and after EWS-FLI1 knock-down.We confirmed a subset of regulated gene targets by qRT-PCR (Fig. S5A). VRK1 is proximal to an EWS-FLI1 dependent enhancer that is active in Ewing sarcoma cell lines and primary tumors and induced de novo by the fusion protein in MSCs (Fig. 5C).Chromatin conformation studies (3C) confirmed the long distance interaction between the EWS-FLI1-bound enhancer and the VRK1 promoter in both SKNMC and A673 cells (Fig. 5D and E, respectively). VRK1 protein expression was confirmed in 15/15 primary Ewing sarcoma samples analyzed by immunohistochemistry, which revealed strong VRK1 signals in virtually all cells (Fig.6A and Fig. S5B). EWS-FLI1 knock-down markedly reduced VRK1 expression in the cell lines, while EWS-FLI1 induction was sufficient to up-regulate this kinase in MSCs (Fig. 6B and S5C). 25453760 chr2 167687771 167689503 Irf8 We show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. mouse Low+High throughput A Negative Feedback Loop of Transcription Factors Specifies Alternative Dendritic Cell Chromatin States 否 -- monocyte cells E_02_0885 ChIP-seq,ATAC-seq analysis of active enhancers (H3K27ac) revealed the same relationship between H3K27ac intensity and cell type specific genes. ChIP-Seq of in vivo splenic pDCs showed similar patterns to our in vitro pDC model with respect to H3K4me1 and H3K27ac in enhancer regions associated to pDC and moDC specific genes Enhancer -- qPCR,RNA-seq,Western blot C/EBPbeta,CRP2,IL-6DBP,LAP,LIP,NF-IL6,NF-M,Nfil6 -- -- -- 5730422P05Rik,ASP-I2,E2-2,E2.2,ITF-2,ITF-2b,ITF2,ME2,MITF-2A,MITF-2B,SEF-2,SEF2,SEF2-1,TFE,Tcf-4,bHLHb19,Spi-B,2810047E18Rik,BCL-11A,Ctip1,D930021L15Rik,Evi9,Evi9a,Evi9b,Evi9c,mKIAA1809 ATAC-seq,ChIP-seq -- -- Cebpb Tcf4,Spib,Bcl11a Taken together,our results suggest that Irf8 and Cebpb form a double negative feedback loop and a positive self-auto-regulatory loop.Such a composite self-reinforcing negative feedback loop confers bi-stability,leading to either expression of one TF or the other;as a consequence, the entire epigenetic landscape is directed towards either a pDC or moDC Enhancer state. To better focus on open chromatin accessible to TF binding within these Enhancers, we narrowed down our search to overlapping peak of ATAC-seq signal. 25381333 chr22 42411333 42413643 CYP2D6 To characterize the CYP2D6 enhancer element,we applied chromatin conformation capture combined with the next-generation sequencing (4C assays) and chromatin immunoprecipitation with P300 antibody, in HepG2 and human primary culture hepatocytes. human Liver Low throughput Functional characterization of CYP2D6 enhancer polymorphisms 相关 rs133333 -- Primary human hepatocytes E_02_0886 4C,ChIP To search for regions that interact with the CYP2D6 promoter, we performed 4C assays with the CYP2D6 promoter as an anchor.With the exception of R1 and R6, peak signals were all associated with an annotated gene locus (gene body, promoter or upstream region, R2, R3, R4, R5 and R7), suggesting cross-regulation between genes. R1 corresponds to the previously identi?ed downstream enhancer region (7), while R6 appears to be novel. To test whether any of these regions could serve as an enhancer, we performed ChIP assays with an antibody against P300, a universal transcription co-factor that binds to enhancer elements. R1 and R2 displayed the highest signals in both HepG2 and hepatocytes (Fig. 1B and C), consistent with R1 serving as an enhancer for CYP2D6, while R2 corresponds to the 3′ end of CYP2D6, indicative of active transcription of CYP2D6 in both cells. R6 showed low ChIP signals in both cells, arguing against an enhancer role. Enhancer 4C ChIP CPD6,CYP2D,CYP2D7AP,CYP2D7BP,CYP2D7P2,CYP2D8P2,CYP2DL1,CYPIID6,P450-DB1,P450C2D,P450DB1 A region 115 kb downstream of CYP2D6 as Enhancer for CYP2D6, containing two completely linked SNPs, rs133333 and rs5758550, associated with enhanced transcription. DNaseI Accessibility Assay,qPCR,CRISPR/Cas9 To determine the relative chromatin accessibility along the R1 region, we performed DNaseI accessibility assays in both HepG2 and primary human hepatocytes, followed by real-time PCR (12). As expected, the region surrounding rs5758550 (A5) showed the highest accessibility in both cell types (Fig. 4), consistent with its role as enhancer.Among three highly linked SNPs in this region, we identify rs5758550 as the causative variant that regulates enhancer activity, with the minor allele rs5758550G displaying higher activity than the major allele rs5758550A. Moreover, using CRISPR-mediated genomic deletion in HepG2 cells, we demonstrate that deletion of the enhancer region surrounding rs5758550 by 70% decreased CYP2D6 mRNA level >2-fold. -- -- 42412365 4C,ChIP,Luciferase Reporter Assay,PCR CYP2D6 -- To search for regions that interact with the CYP2D6 promoter, we performed 4C assays with the CYP2D6 promoter as an anchor.With the exception of R1 and R6, peak signals were all associated with an annotated gene locus (gene body, promoter or upstream region, R2, R3, R4, R5 and R7), suggesting cross-regulation between genes. R1 corresponds to the previously identi?ed downstream enhancer region (7), while R6 appears to be novel. To test whether any of these regions could serve as an enhancer, we performed ChIP assays with an antibody against P300, a universal transcription co-factor that binds to enhancer elements. R1 and R2 displayed the highest signals in both HepG2 and hepatocytes (Fig. 1B and C), consistent with R1 serving as an enhancer for CYP2D6, while R2 corresponds to the 3′ end of CYP2D6, indicative of active transcription of CYP2D6 in both cells. R6 showed low ChIP signals in both cells, arguing against an enhancer role. -- 25369933 chr15 63254341 63256341 Myc The protooncogene c-Myc (Myc) is a critical target of Notch in normal and malignant pre-T cells, but how Notch regulates Myc is unknown. mouse Low+High throughput Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia 否 Acute Lymphoblastic Leukemia T cell E_02_0887 ChIP-seq,EMSA,3C Notch1 is depleted from the NDME site by short-term gammasecretase inhibitor (GSI) treatment, and loading and unloading of Notch1 is associated with rapid changes in H3K27ac, features that characterize genomic Notch1 binding sites that dynamically regulate gene expression.Notch1 also bound the NDME in primary murine T-ALL cells and in DN3 thymocytes, a stage of T-cell development marked by high levels of Notch1 activation Enhancer 3C ChIP,qRT-PCR,Luciferase Reporter Assay AU0167572,Niard,Nird,bHLHe39,?Myc Altered long-range enhancer activity can mediate resistance to targeted therapies and provide a mechanistic rationale for combined targeting of Notch and Brd4 in leukemia. 3C To determine whether Notch signaling was required to maintain the interaction between the Myc promoter and the NDME,3C analysis was performed in T6E cells cultured in the presence or absence of GSI. 9930111A19Rik,Mis6,N1,Tan1,lin-12 ChIP-seq,3C -- -- Myc,Myc Notch,Notch Schematic of the Luciferasegene constructs including the NDME WT and mutant sequences.To test for chromatin looping between the NDME and the Myc promoter, chromatin conformation capture (3C) assays were carried out in T6E cells.;Schematic of the Luciferasegene constructs including the NDME WT and mutant sequences.To test for chromatin looping between the NDME and the Myc promoter, chromatin conformation capture (3C) assays were carried out in T6E cells. Analysis of the ChIP-seq data revealed an RBPJ/Notch1 binding site associated with high levels of H3K4me1 marks located 1.43 Mb 3′ of the Myc promoter (Fig. 4A) that shares sequence homology with the murine NDME.;Analysis of the ChIP-seq data revealed an RBPJ/Notch1 binding site associated with high levels of H3K4me1 marks located 1.43 Mb 3′ of the Myc promoter (Fig. 4A) that shares sequence homology with the murine NDME. 25321476 chr10 34385685 34385834 Col10a1 Meanwhile, as a specific marker of hypertrophic chondrocytes, the type X collagen gene (COL10A1) is also critical for endochondral bone formation, as mutation and altered COL10A1 expression are often accompanied by abnormal chondrocyte hypertrophy in many skeletal diseases. mouse Low throughput Identification and characterization of the novel Col10a1 regulatory mechanism during chondrocyte hypertrophic differentiation 否 Skeletal Diseases MCT Cell，T cell E_02_0888 Transgenic mice,ChIP,qRT-PCR,EMSA These results show that multiple copies of the enhancer (150-bp Col10a1 distal promoter) mediates higher level and cellspecific reporter activity, whereas the 10-kb Col10a1 promoter/intronic element contains nonspecific regulatory elements,in addition to the 150-bp enhancer. Enhancer -- ChIP,qRT-PCR,EMSA Col10,Col10a-1 -- -- -- AML3,Cbf,Cbfa-1,Cbfa1,LS3,Osf2,PEBP2aA,Pebp2a1,Pebpa2a qRT-PCR,EMSA -- -- Col10a1 Runx2 Top panel displays Col10a1 gene structure and the 10 -kb promoter and intronic element.Positions of the 150-bp (?4296 to ?4147 bp) Col10a1 cis-Enhancer (purple bar) and its 330-bp (?220 to +110 bp) basal promoter (red bar) are shown. The qRT-PCR was performed to examine the mRNA transcript level of marker genes Col10a1 and Runx2 in MCT cells. As illustrated, both Col10a1 and Runx2 are significantly upregulated in hypertrophic MCT cells compared with that in proliferative MCT cells. 25303440 chr7 94002773 94005073 COL1A2 Gene activa_x0002_tion was determined by assessing the interaction of transcription factors with the COL1A2 enhancer using transient transfection of reporter gene constructs, elec_x0002_trophoretic mobility shift assays, chromatin immuno_x0002_precipitation analysis, and RNA interference involving knockdown of individual AP-1 family members. human Skin Low throughput Failed Degradation of JunB Contributes to Overproduction of Type I Collagen and Development of Dermal Fibrosis in Patients With Systemic Sclerosis 不相关 Systemic Sclerosis fibroblast E_02_0889 Luciferase Reporter Assay TGFβ is a potent inducer of the human procollagen type I α2 chain gene ( COL1A2). We have recently described in detail the in vivo mechanism underlying the transcriptional control of COL1A2, through a complex interaction between its distal enhancer and proximal promoter, in response to TGFβ. Reporter gene constructs containing the wild-type human enhancer region and the heterologous thymidine kinase (TK) promoter, lacking a Smad-dependent T RE (21.1/18.8pLAC-TK), were used to assess the TβRE in the FUE region. The results indicated that the COL1A2-FUE was activated by TGFβ in both normal and scleroderma fibroblasts. Enhancer -- Luciferase Reporter Assay,EMSA,ChIP,siRNA EDSARTH2,EDSCV,OI4 Binding of JunB to the COL1A2 enhancer was observed, with its coalescence directed by activation of gene transcription through the proximal promoter. ChIP RNA polymeraseII also coprecipitated with the F2 Enhancer sequence,despite not being able to bind the Enhancer directly,thereby demonstrating the interaction between the transcriptional machinery in the promoter with the factors bound to the F2 region. AP-1,AP1,C-JUN, CJUN,P39 EMSA,ChIP -- -- COL1A2 JUNB,JUND Gene activation was determined by assessing the interaction of transcription factors with the COL1A2 Enhancer using transient transfection of reporter gene constructs,electrophoretic mobility shift assays,chromatin immunoprecipitation analysis,and RNA interference involving knockdown of individual AP-1 family members. Supershift assays using specific antibodies (Figure 2B) revealed that normal nuclear extracts bound c-Jun and, to a lesser extent, JunD. In SSc, c-Jun binding was greatly reduced, and JunB, which was previously absent in normal nuclear extracts, accounted for 2 of the shifted bands. JunD binding was more pronounced in SSc extracts (Figure 2B). These gel-shift findings suggest that in SSc dermal fibroblasts or in normal nuclea extracts treated with TGF , JunB binding replaces c-Jun binding on the AP-1 site in the upstream enhancer.These results were confirmed using ChIP assays,which demonstrated the association of the F2 region in the FUE with the proximal promoter and the transcriptional machinery. 25271055 chr11 102006458 102008458 MEF2C Finally, increased sclerostin production achieved by HDAC5 shRNA is abrogated by simultaneous knockdown of MEF2C, indicating that MEF2C is a major target of HDAC5 in osteocytes. human HDAC5-/- Low throughput HDAC5 controls MEF2C-driven sclerostin expression in osteocytes 否 -- Osteocyte Cell Lines E_02_0890 Luciferase Reporter Assay,ChIP Three lines of evidence support a direct role for HDAC5 in regulating MEF2C activity at the +45 kB SOST enhancer over the course of osteocyte differentiation. First, HDAC5 shRNA causes increased activity of this element, but not of the proximal SOST promoter, in luciferase assays. MEF2C shRNA reduces the activity of this enhancer. Second, HDAC5 overexpression dose-dependently inhibits the activity of a MEF2-driven reporter from the desmin and the SOST’9’ (+45kB) enhancer. Third, endogenous HDAC5 association with this region in control (but not HDAC5 shRNA) Ocy454 cells can be detected by ChIP. Enhancer -- ChIP,qRT-PCR,Western blot 5430411E23Rik -- -- -- 5430401D19Rik,9930028G15Rik,AV011172,Mef2 ChIP,PCR -- -- Sost,Sost,Sost Mef2c,Mef2c,Mef2c Using Chromatin immunoprecipitation,we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic Enhancer 45 downstream from the transcription start site.;Using Chromatin immunoprecipitation,we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic Enhancer 45 downstream from the transcription start site.;Using Chromatin immunoprecipitation,we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic Enhancer 45 downstream from the transcription start site. We performed Chromatin immunoprecipitation (ChIP) to determine MEF2C occupancy in Ocy454 cell cultured at 37°C for 14 days (a time point in which SOST expression is High throughput).;We performed Chromatin immunoprecipitation (ChIP) to determine MEF2C occupancy in Ocy454 cell cultured at 37°C for 14 days (a time point in which SOST expression is High throughput).;We performed Chromatin immunoprecipitation (ChIP) to determine MEF2C occupancy in Ocy454 cell cultured at 37°C for 14 days (a time point in which SOST expression is High throughput). 25267720 chr10 43568986 43571244 RET RET is regulated by a distal and a proximal enhancer at its promoter, in which PAX3 and NKX2-1 are the resident transcription factors respectively. human Hirschsprung Low throughput SRY interference of normal regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease 不相关 Hirschsprung Disease neural crest cell E_02_0891 RT-PCR,Luciferase Reporter Assay To determine the probable function of SRY on the transactivation of RET by NKX2-1 and PAX3, we had exam_x0002_ined its effects in a reporter system with a luciferase gene directed by a 3.7 kb promoter (23531 to +196) of the human RET gene(27), harboring both distal and proximal enhancers. Enhancer -- Luciferase Reporter Assay CDHF12,CDHR16,HSCR1,MEN2A,MEN2B,MTC1,PTC,RET-ELE1 -- -- -- CDHS,HUP2,WS1,WS3,BCH,BHC,NK-2,NKX2.1,NKX2A,NMTC1,T/EBP,TEBP,TITF1,TTF-1,TTF1 Luciferase Reporter Assay,GST Pull-down Assay -- -- RET,RET,RET,RET PAX3,NKX2-1,PAX3,NKX2-1,PAX3,NKX2-1,PAX3,NKX2-1 However, when either SOX10 or PAX3 was co-transfected with NKX2-1, significant exacerbations of the RET1.5-luciferase activities were observed (Fig. 2D), suggesting potential interactions and collaborations between these transcription factors and NKX2-1 on regulation of RET gene.;However, when either SOX10 or PAX3 was co-transfected with NKX2-1, significant exacerbations of the RET1.5-luciferase activities were observed (Fig. 2D), suggesting potential interactions and collaborations between these transcription factors and NKX2-1 on regulation of RET gene.;However, when either SOX10 or PAX3 was co-transfected with NKX2-1, significant exacerbations of the RET1.5-luciferase activities were observed (Fig. 2D), suggesting potential interactions and collaborations between these transcription factors and NKX2-1 on regulation of RET gene.;However, when either SOX10 or PAX3 was co-transfected with NKX2-1, significant exacerbations of the RET1.5-luciferase activities were observed (Fig. 2D), suggesting potential interactions and collaborations between these transcription factors and NKX2-1 on regulation of RET gene. SOX10 and SRY competitive interactions with NKX2-1and PAX3 demonstrated by GST pull-down assays,Transfection with either the pM-NKX2-1 or pM-PAX3 expression vectors with the UAS-luciferase reporter showed that the GAL4-BD was indeed capable bringing these two transcription factors to the UAS site, thereby transactivating the UAS-luciferase reporter in the transfected Neuro-2A cells. ;SOX10 and SRY competitive interactions with NKX2-1and PAX3 demonstrated by GST pull-down assays,Transfection with either the pM-NKX2-1 or pM-PAX3 expression vectors with the UAS-luciferase reporter showed that the GAL4-BD was indeed capable bringing these two transcription factors to the UAS site, thereby transactivating the UAS-luciferase reporter in the transfected Neuro-2A cells. ;SOX10 and SRY competitive interactions with NKX2-1and PAX3 demonstrated by GST pull-down assays,Transfection with either the pM-NKX2-1 or pM-PAX3 expression vectors with the UAS-luciferase reporter showed that the GAL4-BD was indeed capable bringing these two transcription factors to the UAS site, thereby transactivating the UAS-luciferase reporter in the transfected Neuro-2A cells. ;SOX10 and SRY competitive interactions with NKX2-1and PAX3 demonstrated by GST pull-down assays,Transfection with either the pM-NKX2-1 or pM-PAX3 expression vectors with the UAS-luciferase reporter showed that the GAL4-BD was indeed capable bringing these two transcription factors to the UAS site, thereby transactivating the UAS-luciferase reporter in the transfected Neuro-2A cells. 25263596 chr1 182851627 182852853 Tet2 By mapping DNA methylation and hydroxymethylation at base resolution, we find that deletion of Tet2 causes extensive loss of 5hmC at enhancers, accompanied by enhancer hypermethylation, reduction of enhancer activity, and delayed gene induction in the early steps of differentiation. mouse Low+High throughput 5mC Oxidation by Tet2 Modulates Enhancer Activity and Timing of Transcriptome Reprogramming during Differentiation 否 -- embryonic stem cell E_02_0892 ChIP-seq,ChIP We therefore hypothesized that loss of Tet2 could lead to reduced oxidation and increased 5mC at enhancers. Indeed, hypermethylated DMRs (hyper-DMRs) in Tet2?/? cells exhibit several hallmarks of enhancers including: evolutionary sequence conservation,enrichment for enhancer chromatin marks H3K4me1 and H3K27ac, and significant overlap with co-activator p300 binding sites (o/e = 5.9, p < 1E-200), DNase I hypersensitive sites(o/e = 4.5, p < 1E-200), and predicted enhancers(o/e = 7.1, p < 1E-200) Enhancer -- PCR,Transgenic mice AI450052,Ebaf,Leftb,Stra3,Tgfb4,lefty,lefty-1 -- -- -- EZF,Gklf,Zie,NF-A3,Oct-3,Oct-3/4,Oct-4,Oct3,Oct3/4,Oct4,Otf-3,Otf-4,Otf3,Otf3-rs7,Otf3g,Otf4,2410002E02Rik,ENK,ecat4,Sox-2,lcc,ysb ChIP-seq -- -- Lefty1 Oct4,Sox4,Nanog Indeed,an Enhancer that physically interacts with the developmental gene Left-Right Determination Factor 1 (Lefty1) is hypermethylated and hypoacetylated in Tet6?/? cells,potentially explaining the significantly decreased expression of this gene. Weaker occupancy of the ES-cell core transcription factors (TFs) OCT4,SOX6,and NANOG than those that do not change DNA methylation status. 25259561 chr7 117075514 117075933 CFTR Cystic fibrosis transmembrane conductance regulator gene (CFTR) expression in human airway epithelial cells involves the recruitment of distal cis-regulatory elements human Epithelial Low throughput Oxidative stress regulates CFTR gene expression in human airway epithelial cells through a distal antioxidant response element. 否 -- bronchial epithelial cell E_02_0893 Luciferase Reporter Assay,EMSA,RT-PCR,ChIP To confirm that DHS-44kb contained an enhancer of CFTR expression, the 0.6-kb DHS fragment (hg 19, chr7:117075400–117076000) was PCR amplified and inserted into the enhancer site of the pGL3B 245 vector.These data suggest that the enhancer activity of the DHS-44kb element is specific to airway epithelial cells. Enhancer -- RT-PCR,ChIP ABC35,ABCC7,CF,CFTR/MRP,MRP7,TNR-CFTR,dJ760C5.1 -- -- -- CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NFKB-p105,NFKB-p50,NFkappaB,p105,p50,BACH-1,BTBD24 EMSA -- -- CFTR NFKB1,BACH1 To determine whether the SFN_x0002_triggered antioxidant response regulates CFTR expression directly through the DHS-44(279) cis-element, ChIP was used to measure the enrichment levels of the constitutive ARE binding factor Bach1, the SFN-induced ARE binding factor Nrf2, and their common partner MafK at this site. EMSAs were performed with 32P-labeled, double-stranded DNA probes for 44-I, 44-II, and 44-III,Moreover, when Bach1 was overexpressed in 16HBE14o- cells by transient transfection of a mouse Bach1 cDNA clone, a strong supershift was seen with the Bach1 antibody and probe 44-I. 25249570 chr9 99131669 99132862 Pik3cb Pik3cb is a crucial direct target of YAP, through which the YAP activates phosphoinositol-3-kinaseAKT pathway and regulates cardiomyocyte proliferation and survival. mouse Heart Low+High throughput Pi3kcb Links Hippo-YAP and PI3K-AKT Signaling Pathways to Promote Cardiomyocyte Proliferation and Survival 否 Heart Injuries ventricular cardiac muscle cell E_02_0894 Luciferase Reporter Assay,ChIP-seq To measure the transcriptional activity of the YAP-bound region of Pik3cb, which we refer to as the Pik3cb enhancer, we cloned a 552 bp genomic DNA fragment containing the conserved element and potential TEAD binding sites into a minimal promoter luciferase reporter construct. Co-transfection with Yap in NRVMs showed that Yap stimulates activity of the enhancer by ~5-fold. Enhancer -- qRT-PCR,ChIP-qPCR 1110001J02Rik,AI447572,p110beta YAP and TEAD occupied a conserved Enhancer within the first intron of Pik3cb, and this Enhancer drove YAP_x0002_dependent reporter gene expression. ChIP-seq,ChIP-qPCR,Luciferase Reporter Assay To measure the transcriptional activity of the YAP-bound region of Pik3cb, which we refer to as the Pik3cb Enhancer, we cloned a 552 bp genomic DNA fragment containing the conserved element and potential TEAD binding sites into a minimal promoter luciferase reporter construct. Co-transfection with Yap in NRVMs showed that Yap stimulates activity of the Enhancer by ~5-fold. AI325207,Yap,Yap65,Yki,Yorkie ChIP-seq,ChIP-qPCR,Luciferase Reporter Assay -- -- Pik3cb Yap1 To measure the transcriptional activity of the YAP-bound region of Pik3cb, which we refer to as the Pik3cb Enhancer, we cloned a 552 bp genomic DNA fragment containing the conserved element and potential TEAD binding sites into a minimal promoter luciferase reporter construct. The HL1 ChIP-seq data revealed a YAP-bound sequence residing in the first intron of Pik3cb (Fig. 2A). We validated YAP binding to the identified sequence by ChIP-qPCR,using a pair of primers spanning the YAP bound sequence and a control pair recognizing a sequence 1.3 kb away. 25248036 chr2 217918268 217921910 IGFBP5 Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology. human Mammary Low+High throughput Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. 是 rs4442975 Breast Cancer breast cancer cell E_02_0895 Luciferase Reporter Assay,ChIP-seq,3C,PCR The strongest candidate for causality, SNP rs4442975, flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5. Furthermore, we demonstrate that rs4442975 is associated with allele_x0002_specific FOXA1 binding, chromatin looping and IGFBP5 expression. Our data suggest that the g-allele of rs4442975 confers increased breast cancer susceptibility through reduced IGFBP5 expression. Enhancer 3C -- IBP5 -- -- -- HNF3A,TCF3A qPCR,ChIP-seq 217920769 ChIP-seq,ChIP,qPCR,ChIP-qPCR,3C IGFBP5 FOXA1 This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology. To assess occupancy of FOXA1 in vivo, we conducted ChIP followed by allele-specific quantitative PCR (qPCR) in the heterozygous BT474 breast cancer cell line. 25223790 chr17 35502632 35504632 Nanog In this study, we set out to systematically evaluate the performance of these two rising technologies in reactivation or repression of endogenous pluripotency genes (Oct4 and Nanog) in reprogramming somatic cells or EpiSCs to iPSCs. mouse Low throughput Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers 否 -- embryonic stem cell E_02_0896 Luciferase Reporter Assay,ChIP,ChIP-qPCR We first investigated activation of the Oct4 enhancer by luciferase reporter assay 48 h after transfection of TALE-A and dCas9-A/gRNA in MEFs. These luciferase constructs contain the 2.4 kb region covering all three upstream regulatory elements of the Oct4 locus Enhancer CRISPR/Cas9 qRT-PCR,Luciferase Reporter Assay NF-A3,Oct-3,Oct-3/4,Oct-4,Oct3,Oct3/4,?Oct4,Otf-3,Otf-4,Otf3,Otf3-rs7,Otf3g,Otf4 -- -- -- EZF,Gklf,Zie,NF-A3,Oct-3,Oct-3/4,Oct-4,Oct3,Oct3/4,Oct4,Otf-3,Otf-4,Otf3,Otf3-rs7,Otf3g,Otf4,2410002E02Rik,ENK,ecat4,Sox-2,lcc,ysb ChIP-seq -- -- Oct4 Klf4,Oct4,Nanog,Sox2 The Oct4 luciferase assay reporter constructs carried the genomic DNA 2.4 kb upstream of the Oct4 transcrip_x0002_tion start site (TSS). The region encompasses the 1.7 kb distal and proximal Enhancers and the 0.2 kb promoter. To address this possibility, we reviewed the ChIP-seq information of several pluripotency transcription factors, including KLF4,OCT4,NANOG and SOX2 at the Nanog 5kb upstream Enhancer region(42) and found that the Site 2 (targeted by both TALE and dCas9) was surrounded by the predicted KLF4 and NANOG binding sites. 25214635 chr10 6064657 6065397 IL2RA We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. human Low throughput Intersection of population variation and autoimmunity genetics in human T cell activation. 是 rs12251836 Autoimmune Diseases T cell E_02_0897 EMSA,Luciferase Reporter Assay We first tested for enhancer activity by introducing ~200 bp fragments centered around each SNP (Fig. 6A) into a luciferase reporter vector, driven by SV40 or IL2RA minimal promoters, and transfecting them into Jurkat T cells.The higher enhancer function of the T allele was dependent on activation of the Jurkat cells (Fig. 6C), suggesting that enhancer activity is boosted upon cell activation by interactions affected by the single base change at rs12251836. Enhancer -- GWAS CD25,IDDM10,IL2R,IMD41,TCGFR,p55 -- -- -- DELTA,GADEVS,INO80S,NF-E1,UCRBP,YIN-YANG-1 EMSA 6091281 Luciferase Reporter Assay,EMSA IL2RA YY1 Together, these results point to functional effects of at least two independent associations in the IL2RA locus, which may have balancing effects. We surmise that the associated variant rs12251836 is mainly active in acutely triggered T effector cells, but not in Treg cells, since IL2RA mRNA in unstimulated CD4+ T cells would predominantly come from CD25hi Treg cells, and this association was not apparent in unstimulated cells. The allele-specific binding of YY1 was also confirmed by EMSA. 25194570 chr8 130179643 130181490 MYC This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.47 Mb from the MYC transcription initiating site, interacts with the MYC proximal promoter and induces orientation-independent MYC expression in reporter assays. human Low+High throughput A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. 否 T-Cell Acute Lymphoblastic Leukemia HPB-ALL,JURKAT,T-acute lymphoblastic leukemia (T-ALL) E_02_0898 ChIP-seq,ChIP,Luciferase Reporter Assay,3C,PCR This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.47 Mb from the MYC transcription initiating site,interacts with the MYC proximal promoter and induces orientation-independent MYC expression in reporter assays.Moreover, luciferase reporter assays showed strong, orientationindependent activation of reporter constructs containing this enhancer in association with a ?2.5 kb MYC proximal promoter21 in JURKAT T-ALL cells,which express high levels of constitutively active NOTCH1 protein 22, but not in Daudi and Raji B-cell lineage cells. Enhancer -- Luciferase Reporter Assay,PCR MRTL,MYCC,bHLHe39,c-Myc -- -- -- AOS5,AOVD1,TAN1,hN1 ChIP,ChIP-seq -- -- MYC NOTCH1 Consistent with this hypothesis, chromatin configuration 3C analysis of the MYC locus demonstrated the association of this enhancer with proximal regulatory sequences in the MYC promoter.Moreover, histological analysis of multiple tissues including those in which NOTCH signaling plays important developmental roles such as breast epithelium, skin, and intestine showed no alterations (Supplementary Fig. 7) and RT-PCR analysis showed no effects of N_x0002_Me deletion in Myc expression. Interestingly, chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-seq) analysis of NOTCH1 chromatin binding sites in HPB-ALL T-ALL cells revealed a prominent 1 kb NOTCH1 peak in chromosome 8q24 located within the common 40 Kb segment duplicated in all these eight leukemia cases. 25030696 chr17 31172998 31173656 Vegfa A set of angiogenic genes, including Vegfa, has liganded RXR-controlled enhancers and provides the macrophage with a novel inducible program. mouse Low throughput The active enhancer network operated by liganded RXR supports angiogenic activity in macrophages 否 -- COS-1 E_02_0899 3C,ChIP,RNA-seq,GRO-seq,Luciferase Reporter Assay Interestingly, primarily RXR-induced eRNA production could be detected on an enhancer assigned to Vegfa or Tgm2, while an enhancer of Abcg1 also showed robust LXR ligand activation, as expected. These data suggested that the eRNAs can be easily validated and show ligand induction similar to the regulated genes and therefore most likely are linked. Enhancer 3C qRT-PCR AW413978,Abc8,White A set of angiogenic genes, including Vegfa, has liganded RXR-controlled enhancers and provides the macrophage with a novel inducible program 3C,3C-seq Using chromosome conformation capture (3C) and 3C combined with sequencing (3C-seq), and we show that selected long-range Enhancers communicate with promoters via stable or RXR-induced loops and that some of the Enhancers interact with each other, forming an interchromosomal network. 9530071D11Rik,Nr2b1,RXRalpha1 RNA-seq,ChIP-seq,GRO-seq,3C-seq -- -- Abcg1 Rxra Box plot representation of the distribution of interaction frequency of Abcg1 B1 Enhancer (chr17: 31,172,998–31,173,656) and Vegfa B1 Enhancer (chr17: 45,890,060–45,890,829) determined by 3C-seq. In our studies, we tried to solve these issues by combining RNA-seq, ChIP-seq, GRO-seq (global run-on sequencing), and 3C-seq (chromosome conformation capture [3C] combined with sequencing) in a highly integrated way to unravel the mechanism of RXR-induced transcriptional events in mouse bone marrow-derived macrophages (BMDMs) and, as the result of the process,discovered and validated a novel biological activity promoted by the receptor. 24916375 chr9 124638991 124641160 BNC2 One example is rs10765819 located in the first intron of the BNC2 gene previously associated with (saturation of) human skin color. human Low+High throughput Human skin color is influenced by an intergenic DNA polymorphism regulating transcription of the nearby BNC2 pigmentation gene. 否 -- LP89 E_02_0900 ChIP-seq,ChIP-qPCR We profiled the chromatin structure of the BNC2 region to identify potential regulatory elements using chromatin immune-precipitation (ChIP) of H3K27Ac (an active-enhancer mark) in combination with next generation sequencing (ChIP-seq) and ENCODE data. We provide evidence that a region upstream from the canonical BNC2 promoter acts as an enhancer regulating the expression of BNC2, and this transcriptional regulation is dependent on the allelic status of an LD partner of the pigmentation-associated SNP rs10756819. Enhancer -- ChIP-seq,RT-qPCR BSN2 -- -- -- -- -- -- -- BNC2 -- We confirmed this finding by RT–qPCR analysis ofBNC2-expression levels atthree different loca_x0002_tions within the gene, using one primer set targeting mRNA upstream of the alternative promoter, and two primer sets targeting the mRNA downstream of the alternative promoter. -- 24915132 chr2 25423079 25423874 Fut7 Fucosyltransferase VII encoded by the gene Fut7 is essential in CD4+ T cells for the generation of E- and P-selectin ligands (E- and P-lig) which facilitate recruitment of lymphocytes into inflamed tissues and into the skin mouse Inflamed Low throughput Identification of two regulatory elements controlling Fucosyltransferase 7 transcription in murine CD4+ T cells 否 -- Th1 Cell E_02_0901 ChIP Incontrast, lung fibroblasts, which are of mesenchymal origin andwhich lack Fut7 mRNA and selectin ligand expression, carried adifferential histone modification pattern with an enrichment ofH3K27me3 at the CNS and the Fut7 gene locus and absenceof H3K4me2 marks. This suggests that the pattern of histone mod-ifications might control tissue-specific expression of Fut7, ratherthan the differentiation and activation dependent expression inT cells Enhancer -- qRT-PCR,Luciferase Reporter Assay AI853193,FTVII,Fuc-TVII,FucT-VII -- -- -- A430090G16,A730011L11,KAT3B,p300,p300 HAT ChIP -- -- Fut7 Ep300 The CNS was cloned in different orientations in the Enhancer position of the pGL3 vector carrying the +728/+1523 construct in promoter position and transfected into Th1 cells. As our histone ChIP data as well as analysis of genome-wide p300 binding data published by Vahedi et al.(2012) revealed distribution ofthe active histone mark as well as enrichment of p300 binding (data not shown) beyond the homology region, i.e. the CNS, we extended the CNS by about 300 bp upstream and 150 bp downstream of the original construct. 24905168 chr4 124638991 124641160 Otx2 Our results illuminate regulatory mechanisms underlying pluripotency and suggest that the capacity of transcription factors such as Otx2 and Oct4 to pioneer new enhancer sites is highly context dependent. mouse Low+High throughput Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency 否 -- embryonic stem cell E_02_0902 ChIP-seq,RNA-seq To address whether changes in enhancer utilization patterns occur in the majority of cells within the differentiating population, we isolated dual transgenic enhancer reporter lines, in which ESC-specific or EpiLC-specific enhancers of interest were cloned upstream of a minimal promoter and one of two distinct fluorescent reporters and integrated into the ESC genome using a PiggyBac transposon system. Enhancer -- qPCR,IP-Western Oct-6,Oct6,Otf-6,Otf6,Scip,Test1,Tst-1,Tst1 -- -- -- E130306E05Rik,2810482H01Rik,NF-A1,Oct-1,Oct1,Otf-1,Otf1 ChIP-seq -- -- Pou3f1 Otx2,Oct4 Upon differentiation, Otx2?/? cells underwent morphological changes indistinguishable from those seen in wt EpiLCs, but showed defects in expression of certain epiblast-associated genes, such as Fgf5 and Oct6. RNA-seq analysis of Otx2?/? EpiLCs identified 260 and 141 genes significantly downregulated or upregulated, respectively, as compared to the genetically-matched wt EpiLCs Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to pioneer new Enhancer sites is highly context dependent. 24842713 chr16 86212040 86271919 FOXF1 We report on two patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) caused by overlapping genomic deletions that included a distant FOXF1 transcriptional enhancer mapping 0.3 Mb upstream to FOXF1 on 16q24.1. human Lung Low+High throughput Two deletions overlapping a distant FOXF1 enhancer unravel the role of lncRNA LINC01081 in etiology of alveolar capillary dysplasia with misalignment of pulmonary veins 否 -- pneumocyte E_02_0903 ChIP-seq,qRT-PCR,ChIP-qPCR Using chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) of histone H3K27 acetylation (H3K27ac), a mark of active enhancers,we first identified enhancer regions in MYCN-amplified Kelly and nonamplified SH-SY5Y cells. Super-Enhancer -- shRNA ACDMPV,FKHL5,FREAC1 -- -- -- CMM8,COMMAD,MI,WS2,WS2A,bHLHe32,DELTA,GADEVS,INO80S,NF-E1,UCRBP,YIN-YANG-1 ChIP-qPCR -- -- FOXF1 MITF,YY1 Here we investigate whether inhibition of transcriptional CDKs can be exploited to disrupt aberrant MYC-driven transcription, using the deregulated expression of MYCN as a model. The MYCN protein shares most of the physical properties of MYC and is considered functionally interchangeable, based on the similarity of their transcriptional programs, the cellular phenotypes they induce, and the ability of MYCN to replace MYC during murine development. Binding of RNA Polymerase II, similarly tested with ChIP-qPCR in LP89, is relatively high at the alternative promoter and region B′′, which has several features consistent with an enhancer element, e.g. high H3K27Ac enrichment low H3K4Me3 enrichment and binding of MITF and YY1. 24788237 chr12 54357811 54358445 HOTAIR During inspecting functional relevance of the rs920778 SNP, we identified a novel intronic HOTAIR enhancer locating between +1719bp and +2353bp from the transcriptional start site through reporter assays. human Esophageal Low throughput The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. 是 rs920778 Esophageal Squamous Cell Carcinoma KYSE-30,KESY-150,ESCC E_02_0904 Luciferase Reporter Assay,PCR Because the ESCC susceptibility SNP rs920778 is located within the HOTAIR intron 2 and previous H3K4me1 and H3K4me3 modi_x0002_fication data suggest that there might be a potential enhancer in this intron,we therefore examined the enhancer activity of this region by a set of luciferase reporter gene constructs in human ESCC KYSE30 and KYSE150 cells These results indicated that there may be a negative regulatory element between +1463bp and +1718bpfrom the transcriptional start site and the core region of this intronic enhancer might exist between +1719bp and +2353bp from the tran_x0002_scriptional start?site. Enhancer -- Luciferase Reporter Assay,PCR HOXAS,HOXC-AS4,HOXC11-AS1,NCRNA00072 The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic Enhancer. ChIP,Luciferase Reporter Assay,PCR Interestingly, the ESCC susceptibility SNP rs920778 in this Enhancer has a genotype-specific effect on lncRNA HOTAIR expression. Our observations also support the hypothesis that functional genetic variants influencing lncRNA regulation may explain a part of ESCC genetic basis. -- -- 54360232 Luciferase Reporter Assay,PCR HOTAIR -- We hypothesized that the functional single nucleotide polymorphisms (SNP) in HOTAIR may affect HOTAIR expression and/or its function and, thus, ESCC risk. Therefore, we examined the association between three haplotype_x0002_tagging SNPs (htSNP) across the whole HOTAIR locus and ESCC risk as well as the functional relevance of an ESCC susceptibility SNP rs920778. -- 24705708 chr6 52199038 52200503 Hoxa4 The Hox gene family encodes homeodomain-containing transcriptional regulators that confer positional information to axial and paraxial tissues in the developing embryo. mouse Lung,Stomach Low+High throughput YY1 Acts as a Transcriptional Activator of Hoxa5 Gene Expression in Mouse Organogenesis 否 -- endothelial cell E_02_0905 EMSA,ChIP A 2.1-kb mesodermal (MES) enhancer important for Hoxa5 paraxial and lateral plate mesoderm expression in the cervico-upper thoracic region of the A-P axis is positioned 39 of the Hoxa5 gene. Enhancer -- Transgenic mice,EMSA,qRT-PCR Vegf,Vpf -- -- -- NF-E1,YY-1 ChIP,qPCR -- -- Vegfa,Vegfa Yy1,Yy1 A 1.5-kb XbaI-XbaI DNA fragment located in Hoxa4-Hoxa5 intergenic sequences at 3.0-kb upstream the Hoxa4 gene (positions +9351-bp to +10816-bp) was able to target Hoxa5 expression in lung and stomach.;A 1.5-kb XbaI-XbaI DNA fragment located in Hoxa4-Hoxa5 intergenic sequences at 3.0-kb upstream the Hoxa4 gene (positions +9351-bp to +10816-bp) was able to target Hoxa5 expression in lung and stomach. In summary, YY1 acts as a positive regulator of Hoxa5 lung, stomach and intestine expression during embryogenesis.;In summary, YY1 acts as a positive regulator of Hoxa5 lung, stomach and intestine expression during embryogenesis. 24703906 chr3 184276287 184278287 GATA2 Transgenic mice harboring a linked BAC developed leukemia accompanied by EVI1 overexpression-neoplasia that was not detected in mice bearing the same transgene but that was missing the GATA2 enhancer. human Colon Low throughput A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. 否 -- Crc Cell,HT-29 E_02_0906 Luciferase Reporter Assay,ChIP,qRT-PCR Importantly, the stimulatory capacity of the ?2.3-kb ECR differed widely among the CRC cell lines and was most pronounced in LS174T cells with highest levels of endogenous EPHB3. Thus, the EPHB3 ?2.3-kb ECR functions as a cell type-specific transcriptional enhancer. Consistent with its evolutionary conservation, also the corresponding region from the mouse EphB3 gene has enhancer properties and exhibits a remarkably similar cell-type specificity in CRC cell lines.We probed these features by chromatin immunoprecipitation (ChIP) and formaldehyde_x0002_assisted isolation of regulatory elements (FAIRE). Enhancer -- ChIP,qRT-PCR EK2,ETK2,HEK2,TYRO6 -- -- -- ASH2,HASH2,MASH2,bHLHa45 Luciferase Reporter Assay -- -- EPHB3 ASCL2 Next, we performed ChIP experiments to investigate the distri_x0002_bution of the histone modifications H3K4me1 and H3K27ac,the acetyltransferase p300, and the Wnt pathway effector TCF7L2 at the EPHB3 locus.Significantly,its cell type-specific activity matches the expression of the endogenous EPHB3 gene in CRC cell lines, suggesting that differences in enhancer function underlie differential EPHB3 expression in CRC. we generated luciferase-reporter constructs with point mutations in the TBE and the binding sites for RBPJ and ETS factors. 24692107 chr17 44464986 44466986 Runx2 Runx2 is essential for osteoblast differentiation and chondrocyte maturation. mouse Connective Low throughput Dlx5 and Mef2 Regulate a Novel Runx2 Enhancer for Osteoblast-Specific Expression 否 -- Osteoblast-Specific Cell E_02_0907 Luciferase Reporter Assay,ChIP,EMSA and found that a 1.3‐kb region located about 30 kb upstream of the transcription start site of type II Runx2 was highly conserved among all of the species Enhancer -- Transgenic mice,RT-PCR AML3,Cbf,Cbfa-1,Cbfa1,LS3,Osf2,PEBP2aA,Pebp2a1,Pebpa2a -- -- -- AI385752,5430401D19Rik,9930028G15Rik,AV011172,Mef2,AI465550,TCF-1,Tcf1,Bfc,Catnb,Mesc,6430578P22Rik,C22,Osx,AI528653,Mad1,Madh1,Madr1,Mlp1,MusMLP,dwf-A,mMad1,AI987981,SOX-LZ EMSA,ChIP -- -- Runx2,Runx2 Dlx5,Mef2c,Tcf7,Ctnnb1,Sp7,Smad1,Sox6,Dlx5,Mef2c,Tcf7,Ctnnb1,Sp7,Smad1,Sox6 We searched for regulatory elements of the Runx2 gene,and identified a 343bp Enhancer sequence,which specifically directed the reporter gene expression to osteoblasts.;We searched for regulatory elements of the Runx2 gene,and identified a 343bp Enhancer sequence,which specifically directed the reporter gene expression to osteoblasts. In EMSA, Mef2c, Dlx5, and Msx2 but not Tcf7, Ctnnb1, Smad1, Sox6, and Sp7 directly bound to the 89‐bp core sequence.In ChIP analysis, the bindings of Dlx5, Dlx6, Msx2, Mef2, Tcf7, Ctnnb1, Smad1, Sox5, Sox6, and Sp7 to the 343 enhancer region were detected using each antibody, whereas the binding of Foxa2 was not detected in primary osteoblasts despite the presence of a conserved Foxa2 binding motif in the core 89‐bp sequence.;In EMSA, Mef2c, Dlx5, and Msx2 but not Tcf7, Ctnnb1, Smad1, Sox6, and Sp7 directly bound to the 89‐bp core sequence.In ChIP analysis, the bindings of Dlx5, Dlx6, Msx2, Mef2, Tcf7, Ctnnb1, Smad1, Sox5, Sox6, and Sp7 to the 343 enhancer region were detected using each antibody, whereas the binding of Foxa2 was not detected in primary osteoblasts despite the presence of a conserved Foxa2 binding motif in the core 89‐bp sequence. 24671955 chr5 139970046 139972237 CD14 We identified differential regulatory elements (including promoters and putative enhancers) that were associated with subset-specific motif signatures corresponding to different transcription factor activities and exemplarily validated novel downstream enhancer elements at the CD14 locus. human Low+High throughput Transcription and enhancer profiling in human monocyte subsets. 否 -- peripheral blood mononuclear cell E_02_0908 RT-PCR,ChIP,Luciferase Reporter Assay,ChIP-seq To extend the analysis of regulatory sites to putative enhancers, we also carried out ChIP sequencing for 2 histone marks, namely H3K4me1 and H3K27ac,that were previously associated with enhancers.30-34 H3K27 is a major substrate for the coactivators p300 and CBP and its acetylation marks active enhancers, whereas H3K4me1 is generally associated with distal regulatory elements, including poised enhancers. Enhancer -- RT-PCR,Luciferase Reporter Assay CD14 -- -- -- -- -- -- -- CD14 -- On this basis, we sought an explanation for the differential ex_x0002_pression of CD14 in classical monocytes. Studies in transgenic mice by Zhang and coworkers established that a region of 80 kb surrounding the human CD14 gene is sufficient to direct its monocyte specific expression,42 whereas smaller constructs recapitulated human liver expression but failed to direct monocyte-specific expression.The genomic interval downstream of the CD14 gene contained a number of H3K27ac-marked sites specific for classical,CD14-expressing monocytes.These sites frequently overlapped with bidirectional enhancers identified using the FANTOM5 expression atlas44 as well as binding sites for PU.1 or C/EBPb in total monocytes,18 which are key factors in establishing distal regulatory sites in these cells. -- 24667089 chr8 141161900 141175436 KCNK9 Utilizing allele-specific RT-PCR, bisulphite sequencing, chromatin immunoprecipitation and chromosome conformation capture (3C) we show the reciprocal expression of the novel, paternally expressed, PEG13 non-coding RNA and maternally expressed KCNK9 genes in brain, and the biallelic expression of flanking transcripts in a range of tissues. human lymphoid Low throughput The PEG13-DMR and brain-specific enhancers dictate imprinted expression within the 8q24 intellectual disability risk locus. 否 Intellectual Disability Lymphoblastoid cell lines E_02_0909 RT-PCR,ChIP,Luciferase Reporter Assay,3C,DNaseI-seq Using 3C, we identify mutually exclusive approximately 58 and 500 kb chromatin loops in adult frontal cortex between a novel brain-specific enhancer, marked by H3K4me1 and H3K27ac, with the KCNK9 and PEG13 promoters which we propose regulates brain-specific expression. Enhancer 3C RT-PCR,ChIP K2p9.1,KT3.2,TASK-3,TASK3 -- -- -- MRD21 3C-qPCR -- -- KCNK9 CTCF Utilizing allele-specific RT-PCR, bisulphite sequencing, chromatin immunoprecipitation and chromosome conformation capture (3C) we show the reciprocal expression of the novel, paternally expressed, PEG13 non-coding RNA and maternally expressed KCNK9 genes in brain, and the biallelic expression of flanking transcripts in a range of tissues. 3C-qPCR assays were performed on cerebellar samples and interaction frequencies were determined between a constant HindIII site located within the unmethylated CTCF-cohesin binding site within the KCNK9 promoter and other HindIII sites throughout the locus. We identified strong interactions between the KCNK9 promoter constant fragment with the PEG13-DMR and the CTCF-cohesin site in the enhancer region located within intron 17 of TRAPPC9. 24594601 chr8 128230172 128243000 MYC We also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. human Colon Low throughput Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. 是 rs6983267 Colorectal Cancer HCT 116,RKO E_02_0910 qRT-PCR,3C The enhancer region showed long-range in_x005f_x0002_teraction with MYC (?335 kb from the region),suggesting that the enhancer region could regulate CARLo-5 (?180 kb from the region) expression by enhancing its transcription through direct interaction. To test this possibility, we performed chro_x0002_mosome conformation capture (3C) analysis using genomic DNA from CRC-derived HCT116 and RKO cells.The results of 3C analysis show that the enhancer region physically interacts with CARLo-5. Enhancer 3C qRT-PCR CARLO5,CARLo-5,onco-lncRNA-40 The MYC Enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC Enhancer with the CARLo-5 promoter regulates CARLo-5 expression. 3C,qRT-PCR,siRNA We also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, we demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. -- -- 128413305 qRT-PCR,3C CCAT1 -- These results demonstrate that the enhancer region may regulate expression of CARLo-5 by direct interaction with the active regulatory 5′ promoter region of CARLo-5.These results suggest that the cancer-associated variant rs6983267 in MYC enhancer could regulate CARLo-5 expression through long-range interaction with the active regulatory region of its promoter. -- 24512546 chr8 128709135 128745673 FOXA1 Increasing evidence suggests that forkhead box A1 (FOXA1) is frequently dysregulated in many types of human cancers. human Endometrial Low+High throughput FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer. 否 Endometrial Cancer AN3 CA,RL95-2,HEC-1-B E_02_0911 ChIP,ChIP-PCR,ChIP-seq,qRT-PCR Interestingly, we showed that FOXA1 and AR more evidently bound to the MYC enhancer regions as compared to MYC promoter regions. These results could be attributed to other co-regulators involved in this binding process. Since TCF7L2, a protein mediating DNA looping for long-distance interactions of distal en_x0002_hancers and proximal promoters, physically interacts with FOXA1 and AR and mediates the transcription of MYC in breast cancer [19], future investigation will be needed to clarify which co-regulators are involved in FOXA1/AR binding to the enhancer regions upstream of MYC in EC cells. Enhancer -- ChIP,ChIP-PCR,qRT-PCR MRTL,MYCC,bHLHe39,c-Myc -- -- -- HNF3A,TCF3A,AIS,AR8,DHTR,HUMARA,HYSP1,KD,NR3C4,SBMA,SMAX1,TFM ChIP,ChIP-PCR,ChIP-seq,qRT-PCR -- -- MYC,MYC FOXA1,AR,FOXA1,AR Our ChIP assays showed that both FOXA1 and AR could bind to all the five putative FOXA1-AR-binding regions in MFE-296 cells. More_x0002_over, both FOXA1 and AR bound most greatly to the Enh-1 (enhancer 1) region among the five binding regions (Figure 4D). Our ChIP data together with our co_x0002_immunoprecipitation data suggested that FOXA1 forming protein complex with AR might bind to FOXA1-AR over_x0002_lapping binding regions upstream of MYC, leading to MYC activation in EC cells.;Our ChIP assays showed that both FOXA1 and AR could bind to all the five putative FOXA1-AR-binding regions in MFE-296 cells. More_x0002_over, both FOXA1 and AR bound most greatly to the Enh-1 (enhancer 1) region among the five binding regions (Figure 4D). Our ChIP data together with our co_x0002_immunoprecipitation data suggested that FOXA1 forming protein complex with AR might bind to FOXA1-AR over_x0002_lapping binding regions upstream of MYC, leading to MYC activation in EC cells. Our ChIP assays showed that both FOXA1 and AR could bind to all the five putative FOXA1-AR-binding regions in MFE-296 cells. More_x0002_over, both FOXA1 and AR bound most greatly to the Enh-1 (Enhancer 1) region among the five binding regions.;Our ChIP assays showed that both FOXA1 and AR could bind to all the five putative FOXA1-AR-binding regions in MFE-296 cells. More_x0002_over, both FOXA1 and AR bound most greatly to the Enh-1 (Enhancer 1) region among the five binding regions. 24498324 chr11 47363009 47364009 CTCF CCCTC-binding factor (CTCF) can both activate as well as inhibit transcription by forming chromatin loops between regulatory regions and promoters. human blood Low throughput Epigenetic control of SPI1 gene by CTCF and ISWI ATPase SMARCA5 Acute Myeloid Leukemia bone marrow cell E_02_0912 ChIP Using ChIP we focused on loci with more than 2-fold occupancy relative to control antibody. We dentified diffuse occupancy of CTCF with peaks involving amplicons -16.6 (downstream URE), -14.4 (Enhancer), and -11 (Element) as well as in the neighboring mplicons: -15.6, -13.7, -13.4, -13.3, -12.4 and also close to the promoter at -0.15. Enhancer -- RT-PCR,Western blot,Luciferase Reporter Assay OF,PU.1,SFPI1,SPI-1,SPI-A -- -- -- -- -- -- -- SPI1 -- To conclude this part,CTCF and SMARCA5 co-occupy its newly validated target SPI1 using ChIP assay at the -14.4 Enhancer upon AZA-mediated DNA demethylation. -- 24443471 chr7 116374406 116376406 ERBB2 Inhibiting oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is a mainstay of current cancer therapy but is hindered by innate drug resistance mediated by up-regulation of the HGF receptor, MET. human lymph Low throughput Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition Melanoma COLO 829 E_02_0913 3C,ChIP Chromosome conformation capture (3C)was performed in COLO829 cells in the presence or absence of PLX4032 using the MET +63-kb enhancer as an anchor region. We observed that BRAF inhibition strikingly increased the interaction between the MET +63-kb enhancer and the MET TSS, demonstrating that this lineage-specific enhancer undergoes inducible chromatin looping in response to oncogene withdrawal in melanoma cells. Enhancer 3C ChIP AUTS9,DFNB97,HGFR,RCCP2,c-Met This enhancer displays inducible chromatin looping with the MET promoter to up-regulate MET expression upon BRAF inhibition. ChIP,3C ChIP and 3C analysis were performed on wild-type or Enhancer-edited cells treated with PLX4032.A significant decrease in both H3K27 acetylation,a histone modification associated with active Enhancer state,and Enhancer-promoter chromatin looping was observed in Enhancer-edited cells. CMM8,COMMAD,MI,WS2,WS2A,bHLHe32 ChIP-seq,3C -- -- MET MITF Chromosome conformation capture (3C)was performed in COLO829 cells in the presence or absence of PLX4032 using the MET +63-kb Enhancer as an anchor region.We observed that BRAF inhibition strikingly increased the interaction between the MET +63-kb Enhancer and the MET TSS. To test the necessity of MITF for inducible chromatin looping between the MET +63-kb Enhancer and MET TSS in response to BRAF inhibition, 3C was performed in COLO829 cells in the presence or absence of PLX4032 and MITF depletion. 24391766 chr7 100474191 100474841 UCP3 Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein implicated in lipid handling and metabolism of reactive oxygen species. human Brown adipose Low+High throughput A Novel SP1/SP3 Dependent Intronic Enhancer Governing Transcription of the UCP3 Gene in Brown Adipocytes 否 -- HIB1b Cell E_02_0914 Luciferase Reporter Assay,PCR,EMSA,ChIP-seq The first intron of the hamster is shorter compared to mouse and rat corresponding to the first half of the introns in these species.Generally, sequence conservation was low across the first intron,except a region of high conservation ranging from IVS(intervening sequence)1+1200 to IVS1+1850 with the IVS1+1505G/A baseexchange in the center of this region. Enhancer -- Luciferase Reporter Assay,PCR,EMSA AI645527,Slc25a9,UCP-3 This intronic region is the main Enhancer driving UCP3 expression with SP1/3 and PPARc as the core factors required for expression. EMSA,ChIP-seq While we understand that simple EMSA experiments are not sufficient to validate presence of a complex transcription factor binding module conserved across the whole mammalian class, our data provide good evidence that it an intronic Enhancer in the first intron of the UCP3 gene is of importance in non-rodent species as well. 1110003E12Rik,AA450830,AI845540-1,Sp1,D130027J01Rik EMSA,ChIP-seq -- -- Ucp3 Sp1,Sp3 Generally, sequence conservation was low across the first intron,except a region of high conservation ranging from IVS(intervening sequence)1+1200 to IVS1+1850 with the IVS1+1505G/A base exchange in the center of this region. We discovered that the transcription factors SP1 and SP3 were binding to the IVS1+1505G element, whereas binding to the mutant allele was strongly diminished. Direct binding of PPARγ and RXRa to the IVS1+1505G element could be ruled out. 24391132 chr4 147962887 147964479 Nppa Here, we established a noninvasive and quantitative live imaging system for monitoring transcriptional activity and identified a novel stressresponsive enhancer of Nppa and Nppb, the most common markers of heart failure. mouse Heart Low+High throughput Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart 否 Heart Failure 293T cell E_02_0915 RT-PCR,3C,ChIP,Luciferase Reporter Assay Among the 11 CRs identified, only CR9 coincided with the binding sites of RNA polymerase II and p300, and overlapped with the gene areas modified by H3K4me1, and filled all criteria for the enhancer. Enhancer 3C RT-PCR,Transgenic mice AA408272,BNF,BNP -- -- -- CHNG5,CSX,CSX1,HLHS2,NKX2.5,NKX2E,NKX4-1,VSD3,AW108038 ChIP-seq -- -- Nppb,Nppb Nkx2-5,Ctcf,Nkx2-5,Ctcf The Enhancer is a 650-bp fragment within 50 kb of the Nppa and Nppb loci.To identify the organs in which CR9 functioned as a stress-responsive Enhancer, we examined the luciferase reporter expression in each organ by quantitative PCR.;The Enhancer is a 650-bp fragment within 50 kb of the Nppa and Nppb loci.To identify the organs in which CR9 functioned as a stress-responsive Enhancer, we examined the luciferase reporter expression in each organ by quantitative PCR. ChIP-seq data for H3K4me1, p300, and CTCF were obtained from an open database of the adult mouse heart. Some CRs coincided with the peaks for H3K4me1, RNA polymerase II, and the transcriptional coactivator protein p300.;ChIP-seq data for H3K4me1, p300, and CTCF were obtained from an open database of the adult mouse heart. Some CRs coincided with the peaks for H3K4me1, RNA polymerase II, and the transcriptional coactivator protein p300. 24385922 chr6 52296135 52334522 CTCF Interestingly, enhancers located in the same sub-TAD are active in distinct subset of limb cells suggesting that spatial clustering of enhancers does not simply reflect enhancer co-activity. human Low+High throughput Clustering of Tissue-Specific Sub-TADs Accompanies the Regulation of HoxAGenes in Developing Limbs 否 -- Limb,Head E_02_0916 ChIP,PCR,3C,5C,ChIP-seq Sequences distinct from proximal promoters (RefSeq) that were bound by RNAP2 and at least one other mark, or by both p300 and H3K27Ac were retained as candidate enhancers. Using these criteria, 19 putative enhancers were identified within 850 kb upstream of Hoxa13. Enhancer 3C PCR Hox-1 -- -- -- AW108038 5C -- -- Hoxa Ctcf Here,we report on the first identification of bona fide transcriptional Enhancers controlling HoxA genes in developing limbs and show that these Enhancers are grouped into distinct topological domains at the sub-megabase scale. Interestingly,loci bound either by CTCF or cohesin in limb buds have been recently identified and comparison with our data shows that almost all loci interacting with 59 HoxA genes overlap with either CTCF o cohesin binding. 24374176 chr15 37116298 37122452 Meis2 Meis2 repression in early development depends on binding of RING1B, an essential E3 component of PcG, to its promoter, coupled with its association with another RING1B-binding site (RBS) at the 30 end of the Meis2 gene. mouse Fetal Low+High throughput Polycomb Potentiates Meis2 Activation in Midbrain by Mediating Interaction of the Promoter with a Tissue-Specific Enhancer 否 -- embryonic stem cell E_02_0917 ChIP-qPCR,ChIP-seq,ChIP Based on these results, we identified sequence d as a MB Meis2 enhancer, and hereafter designate it as MBE. We went on to look for accumulation of histone H3K27 acetylation (H3K27ac) and H3K4 monomethylation (H3K4me1), which demarcate active and potential enhancers, respectively, at MBE by ChIP-seq. Enhancer -- ChIP-qPCR,ChIP-seq CPCMR,HsT18361,MRG1 -- -- -- BAP-1,BAP1,DING,HIPI3,RING1B,RING2 ChIP-qPCR,ChIP-seq -- -- MEIS2 RNF2 In wild-type mice, Meis2 showed distinctive expres_x0002_sion patterns at 11.5 dpc in FB, MB, pharyngeal arches, spinal cord, neural crest, and somites. In Ring1 mutants, however,we found atypical derepression of Meis2 in facial and cephalic mesenchyme, heart primordium, LM, and somatic mesoderm,coupled with its downregulation in FB and MB (Figure 1C). These results indicate that PcG is involved in both repression and activation of Meis2 in a tissue-specific manner. RING1B ChIP-seq data (GSE48464) over 10 Mb of the mouse genome (mm9) around Meis2 in FB,MB, and LM at 11.5 dpc.Binding of H3K27ac and RING1B in 11.5 dpc MB of WT and Ring1 mutant (Ring1 mut) revealed by ChIP-quantitative PCR (ChIP-qPCR) analysis. 24332044 chr11 110716521 110832306 BRD4 We observe highly asymmetric loading of bromodomain 4 (BRD4) at enhancers, with approximately 33% of all BRD4 localizing to enhancers at 1.6% of occupied genes. human lymphoid Low+High throughput Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. 否 Diffuse Large B-Cell Lymphoma B-Cell Lymphoma Cell Lines E_02_0918 ChIP-seq,ChIP-qPCR As predicted, BRD4 load is asymmetrically distributed throughout the genome at enhancer sites. Completely unexpected is the magnitude by which BRD4 load varies among active enhancer regions (Figure 4E). Only a small subset of BRD-loaded enhancers, 285/18330(1.6%), account for 32% of all of the BRD4 enhancer binding in the cell.The BRD4-loaded enhancers in the Ly1 DLBCL cell line are considerably larger than typical enhancer elements, resembling the super-enhancers we recently described with Richard Young. Super-Enhancer -- ChIP-seq BOB1,OBF-1,OBF1,OCAB These super-Enhancers prove particularly sensitive to bromodomain inhibition,explaining the selective effect of BET inhibitors on oncogenic and lineage-specific transcriptional circuits. ChIP-seq,ChIP-qPCR These super-enhancers prove particularly sensitive to bromodomain inhibition, explaining the selective effect of BET inhibitors on oncogenic and lineage-specific transcriptional circuits. Functional study of genes marked by super-enhancers identifies DLBCLs dependent on OCA-B and suggests a strategy for discovering unrecognized cancer dependencies. E2F-1,RBAP1,RBBP3,RBP3 ChIP-seq,ChIP-qPCR -- -- POU2AF1 E2F1 Notably, the top two gene loci with BRD4-loaded enhancers, POU2AF1 (which encodes the OCA-B transcriptional co-activator protein) and BCL6, and additional genes with disproportionally BRD4-loaded enhancers such as PAX5 and IRF8 (Figure 4E), are essential for B-cell fate determination and germinal center formation. Then, we assessed the genome-wide localization of E2F1 and the representative BET protein, BRD4, also by ChIP-Seq using the respective antibodies. Rank-ordering of all transcriptionally active promoters based on H3K4me3 enrichment and RNA Pol II occupancy identifies pervasive binding of BRD4 and E2F1 to active promoter elements. 24321386 chr17 72860066 72860183 FDXR These results indicated that abundant FDXR expression in these steroidogenic cells was maintained through SF-1 binding to the intronic enhancer of the FDXR gene. human Cervical Low throughput Transcriptional regulation of human ferredoxin reductase through an intronic enhancer in steroidogenic cells. 否 -- HeLa,H295R,KGN E_02_0919 ChIP,Luciferase Reporter Assay,PCR,EMSA Next, histone modifi- cation in the SF-1-induced cells was examined via ChIP assays, using antibodies against two active enhancer markers, histone H3K27ac and H3K4me2, to determine alterations of chromatin state within the region. The results clearly showed that the signals of these active enhancer markers around the SF-1 binding region increased along with the transduction of SF-1 (Fig. 1D and E), suggesting that the transduction of SF-1 led to the active state of chromatin within the FDXR intronic region. Enhancer -- ChIP,Luciferase Reporter Assay,PCR ADR,ADXR,ANOA -- -- -- AD4BP,ELP,FTZ1,FTZF1,POF7,SF-1,SF1,SPGF8,SRXX4,SRXY3,hSF-1 ChIP,qPCR -- -- FDXR NR5A1 Genome-wide analysis of differentiated cells, using a combination of DNA microarray and promoter tiling array analyses, showed that FDXR is a novel SF-1 target gene. In this study,the transcriptional regulatory mechanism of FDXR was examined in steroidogenic cells. Closed and open squares represent Flag-tagged SF-1 (FlagSF-1)- and GFP (Control)-transduced MSCs, respectively; real-time PCR analysis of immunoprecipitated chromatin performed using primers for indicated genomic region; and expressed as a percentage of input. 24285714 chr8 127047315 127049315 Myc Notably, these distal Myc enhancers coincide with a region that is focally amplified in ∼3% of acute myeloid leukemias. mouse Immunohistochem Low+High throughput Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. 否 Acute Leukemia Acute Myeloid Leukemia Cell E_02_0920 ChIP,ChIP-seq,Luciferase Reporter Assay,4C,ChIP-qPCR,3C,qPCR To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 Mb downstream from Myc that are occupied by SWI/SNF as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably,these distal Myc enhancers coincide with a region that is focally amplified in ~3% of acute myeloid leukemias. Enhancer -- ChIP,ChIP-seq,ChIP-qPCR MRTL,MYCC,bHLHe39,c-Myc -- -- -- BAF190,BAF190A,BRG1,CSS4,MRD16,RTPS2,SNF2,SNF2L4,SNF2LB,SWI2,hSNF2b,C/EBP-alpha,CEBP,C/EBP-beta,IL6DBP,NF-IL6,TCF5,erg-3,p55,LMO-2,RBTN2,RBTNL1,RHOM2,TTG2 ChIP-qPCR,shRNA -- -- MYC SMARCA4,CEBPA,CEBPB,ERG,LMO2 To explain this observation, we hypothesized that Brg1 regulates Myc transcription in leukemia cells by occupying cell type-specific regulatory elements. We evaluated this possibility by performing chromatin immunoprecipitation (ChIP) followed by next_x0002_generation sequencing (ChIP-seq) analysis of Brg1, his_x0002_tone H3 Lys 4 trimethylation (H3K4me3), and histone H3 Lys 27 acetylation (H3K27ac) in RN2 leukemia cells. Since all of these TFs are expressed in RN2 cells (Supplemental Fig. 13), we anticipated that these factors would occupy E1–E5 in leukemia as well. Indeed, we detected occupancy of Lmo2, PU.1, and Erg at various subsets of the E1–E5 enhancers in RN2 using ChIP-qPCR (Fig. 5I–K). Additionally, we found that the hematopoietic TFs Cebpα and Cebpβ, both of which are highly expressed in RN2 cells, also occupied the E1–E5 elements (Fig. 5L,M; Supplemental Fig. 13).While expression of several regulators was perturbed upon Brg1 knockdown, Myc was among the most down-regulated genes identified (P < 0.01) (Fig. 3A). Hoxa9, which is a direct target of the MLL-AF9 oncoprotein, was also down-regulated (P < 0.01), albeit to a lesser extent than Myc (Fig. 3A). Gene signatures linked to Myc and Hoxa9 function were globally suppressed following Brg1 knockdown, further confirming an effect on these two pathways (Fig. 3B,C; Supplemental Fig. 5). 24257627 chr2 119321593 119322529 Foxn4 Our data together thus suggest that the mosaic expression of Foxn4 and proneural factors may serve as the trigger to initiate asymmetric Dll4-Notch and subsequent BMP/TGFβ signaling events required for neuronal diversity in the V2 domain. mouse Low throughput Asymmetric activation of Dll4-Notch signaling by Foxn4 and proneural factors activates BMP/TGFβ signaling to specify V2b interneurons in the spinal cord 否 -- 293T,Progenitor Cell E_02_0921 ChIP,PCR,EMSA In addition, we carried out chromatin immunoprecipitation (ChIP) assays to show that both Ascl1 and Neurog1 were able to occupy in vivo the critical E-box region of the CR1 Enhancer in cell culture and mouse embryonic neural tubes, whereas no enrichment was shown for control DNA in Dll4 3′ UTR. Enhancer -- EMSA Delta4 Foxn4, Ascl1 and Neurog1 were able to activate gene expression through an evolutionarily conserved Dll4 Enhancer CR1 found to be active in the retina. ChIP,EMSA In addition, we carried out chromatin immunoprecipitation (ChIP) assays to show that both Ascl1 and Neurog1 were able to occupy in vivo the critical E-box region of the CR1 Enhancer in cell culture and mouse embryonic neural tubes, whereas no enrichment was shown for control DNA in Dll4 3′ UTR.Thus, Ascl1 and Neurog factors may bind to the same E-box in the Dll4 Enhancer but have differential effects on Dll4 gene expression. AI225900,ASH1,Mash1,bHLHa46 EMSA,ChIP -- -- Dll4 Foxn4,Ascl1 We performed an electrophoretic mobility shift assay (EMSA) to test whether Ascl1 and Neurog proteins were able to directly bind to the minimal enhancer region using an oligo probe containing the critical E-box (Probe 2) and a control upstream probe that lacks an E-box (Probe 1) We performed an electrophoretic mobility shift assay (EMSA) to test whether Ascl1 and Neurog proteins were able to directly bind to the minimal Enhancer region using an oligo probe containing the critical E-box (Probe 2) and a control upstream probe that lacks an E-box. 24204311 chr19 10215891 10216703 Sox10 we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. mouse Low throughput The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes 否 -- Oligodendrocytes E_02_0922 ChIP,Luciferase Reporter Assay,EMSA,qPCR Considering the large number of potential Sox binding sites and the low predictive power of their presence, we decided to assess regulatory potential and Sox10-responsiveness of the ECR in luciferase assays.To verify that Sox10 is bound to ECR9 in OL we next performed chromatin immunoprecipitation (ChIP) experiments. Some were clustered so that eight oligonucleotides were sufficient to cover all sites in electrophoretic mobility shift assays (EMSA). Enhancer -- Immunoprecipitation 6030439E18,Gm1804,Gm98,Mrf -- -- -- Dom,Sox21,gt ChIP -- -- Myrf Sox10 To address this issue we performed immunoprecipitation experiments with anti-Sox10 antibodies on extracts of the OL-like OLN93 cell line. To verify that Sox10 is bound to ECR9 in OL we next performed chromatin immunoprecipitation (ChIP) experiments. 24157522 chr5 28476034 28479024 Shh In mouse embryonic endodermal tissues, the seamless expres_x0002_sion of Shh is achieved by a patchwork of multiple enhancers with different rates of evolution. mouse Low+High throughput A novel regulatory element for Shh expression in the lung and gut of mouse embryos 是 -- Colon Adenocarcinoma Cell Lines E_02_0923 RT-PCR,ChIP-seq,Transient Transfection Assay,Luciferase Reporter Assay,3C,DNaseI-seq The ChIP-seq data of the ENCODE project show that H3K4me1, but not H3K4me3, marks all four DNaseI HS sites in the adult lung.To examine whether each of the DNase I HS sites is responsible for upregulating the expression of Shh, we employed a transgenic reporter assay using BAC clones (Figs. 1A and 3A). Enhancer 3C Luciferase Reporter Assay 9530036O11Rik,Dsh,Hhg1,Hx,Hxl3,M100081NC,Shh Shh expression in the endodermal epithelial lining, which is enabled by the coordinated actions of the Enhancers, is necessary for proper endodermal development. RT-PCR,Luciferase Reporter Assay,3C We identified a novel, less-conserved cis-regulatory element for Shh expres_x005f_x0002_sion in the esophageal epithelium, as well as in the lung and intestinal epithelium, in a region 100 Kb upstream of the Shh CDS. The new element compensates for the Enhancer activi_x0002_ties of the three previously identified Enhancers, and the combined activities of all four Enhancers permit the seamless Shh expression in the epithelial linings of the whole endoder_x0002_mal tissues in the mouse embryo. Fox-3,Hrnbp3,NeuN,Neuna60,Cish1,Cish3,JAB,SOCS-1,SSI-1 DNaseI-seq -- -- Shh Rbfox3,Socs1 To determine whether SLGE physically interacts with the Shh promoter in association with transcriptional activity, we conducted a 3C assay, which has been used to measure associations between two genomic regions. Assessment of the functional properties of SLGE by 3C and luciferase assays. Putative binding sites for Fox transcription factors and STAT are found in the SLGE.In human cancer cell lines, including Caco-2, putative Fox- and STAT-binding sites are found in some of the DNase I HS sites around the SHH CDS. 24086551 chr1 1083900 1085900 ZEB1 We therefore compared the expression pattern of miR-200b eRNA with miR-200b~200a~429 gene cluster and other epithelial (E-Cadherin) and mesenchymal (ZEB1) genes in a panel of breast cancer cell lines. human Low+High throughput Identification of an Enhancer That Increases miR-200b~200a~429 Gene Expression in Breast Cancer Cells 否 -- HMLE E_02_0924 qRT-PCR,Luciferase Reporter Assay,ChIP-seq,ChIP-qPCR We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and mesenchymal cell lines using chromatin immunoprecipitation assays and DNA methylation analysis. We discovered a novel enhancer located approximately 5.1kb upstream of the miR-200b~200a~429 transcriptional start site. This region was associated with the active enhancer chromatin signature comprising H3K4me1, H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Enhancer -- qRT-PCR,Luciferase Reporter Assay,ChIP-qPCR GIHCG The presence of a novel Enhancer contributes to miR-200b~200a~429 transcriptional regulation in epithelial cells. Luciferase Reporter Assay Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little effect on miR-200b~200a~429 promoter activity and its production did not correlate with miR-200b~200a~429 gene expression. -- -- -- -- GIHCG -- Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. -- 24040411 chr19 57566145 57571006 Peg3 The promoters of several imprinted genes in the Peg3 domain interact with one evolutionarily conserved region, ECR18, and further suggest that ECR18 may play key roles in the transcription and imprinting control of the Peg3 domain as a distant regulatory element. mouse Low throughput Identification of an evolutionarily conserved cis-regulatory element controlling the Peg3 imprinted domain 否 -- HeLa,HEK-293 E_02_0925 Luciferase Reporter Assay,PCR,3C,ChIP The observed interaction is most prominent in brain, but was also detected in testis. Histone modification and DNA methylation on ECR18 show no allele bias, implying that this region is likely functional on both alleles. In vitro assays also reveal ECR18 as a potential enhancer or repressor for the promoter of Peg3. Overall, these results indicate that the promoters of several imprinted genes in the Peg3 domain interact with one evolutionarily conserved region, ECR18, and further suggest that ECR18 may play key roles in the transcription and imprinting control of the Peg3 domain as a distant regulatory element. Enhancer 3C Luciferase Reporter Assay,PCR PW1,ZKSCAN22,ZNF904,ZSCAN24 ECR18 may play key roles in the transcription and imprinting control of the Peg3 domain as a distant regulatory element. 3C,ChIP In the current study, we performed a series of Chromatin Conformation Capture (3C) and Chromatin Immunoprecipitation (ChIP) analyses to further confirm this prediction. Overall, the current study identifies one region, ECR18, as a key regulatory region for the transcription and imprinting of the Peg3 domain. -- -- -- -- PEG3 -- In the current study, the chromatin conformation capture (3C) method was utilized to detect potential interactions of these ECRs with the imprinted genes. According to the results, one region, ECR18, located 200-kb upstream of Peg3 interacts with the two promoter regions of Peg3 and Zim2. The observed interaction is most prominent in brain, but was also detected in testis. -- 24014243 chr5 107680655 107682655 Mysm1 Mysm1 is a recently identified histone H2A deubiquitinase with essential and intrinsic roles for maintaining functional HSCs. mouse Low throughput The control of hematopoietic stem cell maintenance, self-renewal, and differentiation by Mysm1-mediated epigenetic regulation 否 -- hematopoietic cell,B cell,T cell E_02_0926 ChIP,PCR,Luciferase Reporter Assay To investigate whether Mysm1 regulates Gfi1 expression by binding to the regulatory elements of Gfi1 in HSC, we performed chromatin immunoprecipitation (ChIP) assays along the Gfi1 regulatory elements. A panel of PCR primers to encompass the 23.4-kb promoter and 235-kb enhancer of the Gfi1 locus was designed (Figure 5A). Enhancer -- ChIP,PCR AW495828,Gfi-1,Pal-1,Pal1 -- -- -- Gata-2,AML1,CBF-alpha-2,Cbfa2,Pebp2a2,Pebpa2b Luciferase Reporter Assay,ChIP,PCR -- -- Gfi1 Gata2,Runx1 To investigate whether Mysm1 regulates Gfi1 expression by binding to the regulatory elements of Gfi1 in HSC, we performed chromatin immunoprecipitation (ChIP) assays along the Gfi1 regulatory elements. A panel of PCR primers to encompass the 23.4-kb promoter and 235-kb enhancer of the Gfi1 locus was designed (Figure 5A). Mechanistic studies revealed that Mysm1 modulates histone modifications and directs the recruitment of key transcriptional factors such as Gata2 and Runx1 to the Gfi1 locus in HSCs. We found that Mysm1 directly associates with the Gfi1 Enhancer element and promotes its transcription through Gata2 and Runx1 transactivation. 24000349 chr17 40206839 40206900 Pgk2 Here, we show that chromatin remodeling including reconfiguration of nucleosomes and changes in histone modifications is also associated with transcriptional activation of the Pgk2 gene during spermatogenesis. mouse Low throughput Sequence-specific promoter elements regulate temporal-specific changes in chromatin required for testis-specific activation of the Pgk2 gene 否 -- Somatic Spleen cell,Spermatogenic Germ cell E_02_0927 ChIP,qRT-PCR This reflects the fact that both the human and mouse Pgk2 gene promoters contain highly conserved regulatory elements including a GC-box, a CAAT-box and an enhancer region just upstream from the CAAT-box. Enhancer -- ChIP,qRT-PCR Pgk-2,Tcp-2 Activation of Pgk2 transcription is regulated by testis-specific demethylation of DNA and binding of testis-specific transcription factors to Enhancer and core promoter elements. ChIP,qRT-PCR Our results indicate there is an ordered series of molecular events that lead to activation of transcription of the Pgk2 gene in spermatogenic cells, and that these events are signaled by distinct elements in the Pgk2 promoter/Enhancer region. -- -- -- -- Pgk2 -- Our results indicate there is an ordered series of molecular events that lead to activation of transcription of the Pgk2 gene in spermatogenic cells, and that these events are signaled by distinct elements in the Pgk2 promoter/Enhancer region. -- 23873758 chr12 48368959 48369159 COL2A1 COL2A1 gene expression is positively regulated by the NAD dependent protein deacetylase Sirtuin 1 (SirT1), through its ability to bind chromatin regions of the COL2A1 promoter and enhancer. human Low throughput Set7/9 Impacts COL2A1 Expression Through Binding and Repression of SirT1 Histone Deacetylation 否 -- HeLa,HEK-293 E_02_0928 PCR,ChIP Real‐time PCR (qPCR) reactions for ChIP and ChIP reChIP were carried out using primers flanking the COL2A1 promoter start site(–167) to (–65), see illustration in Figure 6A. Additional analyses were performed on the Sox9‐binding enhancer region of COL2A1(?2259) to (?2430). As a negative control, a distal set of primers flanking the intron 38 (?24148) to (?24368) of the COL2A1 gene was used, based on the protocol by Furlan‐Magarill and colleagues. Enhancer -- PCR,ChIP ANFH,AOM,COL11A3,SEDC,STL1 Although Sox9 (SRY‐related high mobility group‐Box gene 9) has been shown to regulate the expression of the COL2A1 gene by binding the Enhancer within the first intron,numerous additional coactivators (eg, LSox5, Sox6, PGC1a, Notch) are involved in activa PCR,ChIP 3D cultures also exhibited augmented mRNA and protein levels of the transcription factors SP1 and Sox9 (Fig. 5A. B), which are known to regulate COL2A1 expression by binding the DNA-motifs of the promoter and Enhancer regions, respectively. SP1,CMD1,CMPD1,SRA1,SRXX2,SRXY10 ChIP -- -- COL2A1 SP1,SOX9 To understand the regulation of the active COL2A1 promoter, we performed ChIP assays using specific primers flanking the promoter start site and enhancer site within the first intron (illustrated in Fig. 6A). We found enhanced occupancy of the DNA‐binding transcription factor SP1 on the promoter start site of 3D cultured cells, whereas passaged cells (P5) showed a slight but insignificant reduction of SP1 (Fig. 6B). Additionally, passaging significantly decreased Sox9 occupancy on the enhancer site. Chromatin immunoprecipitation (ChIP) analyses of 3D cultures showed augmented levels of the DNA‐binding transcription factor SP1, and the histone methyltransferase Set7/9, on the COL2A1 promoter site. 23872150 chr6 161119825 161121825 PLG PLG gene expression is regulated by glucocorticoids, interleukin 6, nerve growth factor, and retinoic acid-related orphan receptor alpha [10 13]. human Low throughput Estrogen modulates plasminogen promoter activity 否 Hypoplasminogenemia Hep G2,MCF-7 E_02_0929 Luciferase Reporter Assay,ChIP,EMSA,PCR An AP3-like (activator protein 3) enhancer element, located 2.4 kb upstream of PLG-TSS, is involved in PLG transcriptional regulationIn summary we demonstrated that estrogen regulates plasminogen promoter activity. The 5’-flanking region of the PLG gene con_x0002_tains several cis-acting elements that are responsive to estrogen.An enhancer located at -11.5 kb confers a dramatic estrogen re_x0002_sponse in reporter assays. Enhancer -- Luciferase Reporter Assay,PCR PLG An AP3-like (activator protein 3) enhancer element, located 2.4 kb upstream of PLG-TSS, is involved in PLG transcriptional regulation. Luciferase Reporter Assay An AP3-like (activator protein 3) enhancer element, located 2.4 kb upstream of PLG-TSS, is involved in PLG transcriptional regulation [20]. In our study we could show that a construct comprising the entire upstream region, containing the AP3 response element (2.4 kb-PLG) was able to further elevate basal luciferase activity 1.7-fold above that of PLG minimal promoters. anon-EST:Posey114,anon-WO02059370.45,CG13094,DH31,DH-II,dh31,DH31,DH[31],DH[[31],Dh[[31]],DH[[31]],Dmel\CG13094,Drm-DH[[31]],drome-DH31,Drome-DH[[31]],ERE Luciferase Reporter Assay -- -- PLG DHII,ERE In our study we could show that a construct comprising the entire upstream region, containing the AP3 re_x0002_sponse element (2.4 kb-PLG) was able to further elevate basal luciferase activity 1.7-fold above that of PLG minimal promoters.The observed increase corresponds well to previously published results [20] and the 2.4 kb-PLG construct represents the most active contiguous promoter fragment analysed in this study. Surprisingly, with E2 stimulation this effect decreased by 54% down to the activity level of the PLG core promoter,although no ERE could be identified within this region. Transcriptional effect of the DHII and/or ERE (_x0003_11.5 kb) enhancers on the heterologous crystallin promoter (cryst) driven luciferase activity in HepG2. 23675462 chr21 43770915 43772915 TFF1 Here, we demonstrate that both MSK1 and MSK2, regulate the phorbol ester 12-O-tetradecanoylphorbol-13-acetate induced expression of the breast cancer marker gene, trefoil factor 1 (TFF1), by phosphorylating H3S10 at its 59 regulatory regions. human Low throughput Mitogen- and Stress-Activated Protein Kinases 1 and 2 Are Required for Maximal Trefoil Factor 1 Induction 否 -- MCF-7 cell E_02_0930 RT-PCR,ChIP To determine whether MSK1 co-occupies the enhancer and UPE with H3S10ph, we performed sequential ChIP assays (re_x0002_ChIP) with mononucleosomes prepared from TPA- treated and formaldehyde-cross linked MCF-7 cell lysates.Together these results show that either MSK1 or MSK2 recruited to the TFF1 UPE and enhancer phopshorylates H3 at S10, leading to the binding of 14-3-3e/f and recruitment of BRG1. Enhancer -- RT-PCR,ChIP BCEI,D21S21,HP1.A,HPS2,pNR-2,pS2 MSK1 and MSK2 belong to different multiprotein complexes but both mediate chromatin remodeling that is required at the Enhancer and UPE for TPA-induced initiation of TFF1 expression in MCF-7 breast cancer epithelial cells. Re-ChIP An AP3-like (activator protein 3) enhancer element, located 2.4 kb upstream of PLG-TSS, is involved in PLG transcriptional regulation [20]. In our study we could show that a construct comprising the entire upstream region, containing the AP3 response element (2.4 kb-PLG) was able to further elevate basal luciferase activity 1.7-fold above that of PLG minimal promoters. MSK1, MSPK1, RLPK,MSK2, RSK-B, S6K-alpha-4 ChIP -- -- TFF1 RPS6KA5,RPS6KA4 Here, we used the high-resolution chromatin immunoprecipi_x0002_tation (ChIP) assay to determine the MSK1, MSK2 and H3S10ph distribution along the regulatory and coding regions of the TFF1 gene in response to ERK-MAPK signaling.With this in mind, we performed ChIP assays with antibodies against H3S10phK14ac to determine the distribution of this dual H3 modification along the TFF1 gene._x0002_ we used the high-resolution chromatin immunoprecipitation (ChIP) assay to determine the MSK1, MSK2 and H3S10ph distribution along the regulatory and coding regions of the TFF1 gene in response to ERK-MAPK signaling. 23644027 chr5 172648612 172649177 NKX2-5 NKX2-5 gene encodes a highly conserved homeobox transcription factor, which is essential to the heart development in embryos and cardiac function in adults. Mutations in NKX2-5 gene have been implicated in diverse types of CHD, including ventricular septal defect (VSD). human Low throughput Two novel and functional DNA sequence variants within an upstream enhancer of the human NKX2-5 gene in ventricular septal defects 否 Congenital Heart Disease leukocyte E_02_0931 PCR,Luciferase Reporter Assay The wild type and variant upstream enhancers (566 bp) were generated with PCR, and then subcloned into BamHI and SalI sites of a luciferase gene expression vector with human NKX2-5 gene promoter, which has been previously reportedll expression constructs were confirmed by direct sequencing.HEK-293 cells were cultured in DMEM with 10% fetal bovine serum,1% glutamine and 1% penicillin/streptomycin under 5% CO2 at 37 °C. Enhancer -- PCR,Luciferase Reporter Assay CHNG5,CSX,CSX1,HLHS2,NKX2.5,NKX2E,NKX4-1,VSD3 The DSVs within the upstream Enhancer of the NKX2-5 gene may contribute to a small number of VSD. Luciferase Reporter Assay To determine the effects of the DSVs on transcriptional activity of the Enhancer,wild type and variant Enhancers were subcloned upstream to the NKX2-5 gene promoter in the Luciferase gene expression vector,which has been previously constructed and reported. Collectively, these results indicated that the activity of the upstream enhancer of the NKX2-5 gene was decreased by the DSVs g.17483564C>T and g.17483576C>G. -- -- -- -- NKX2-5 -- To determine the effects of the DSVs on transcriptional activity of the enhancer, wild type and variant enhancers were subcloned upstream to the NKX2-5 gene promoter in the luciferase gene expression vector, which has been previously constructed and reported,to generate expression constructs pGL3-WT, pGL3-17483557Ins,pGL3-17483564T and pGL3-17483576G. These constructs were then transiently transfected into HEK-293 cells and luciferase activities were measured. The results were shown in Fig. 2. Expression levels of pGL3-17483564T and pGL3-17483576G were significantly decreased compared to pGL3-WT. -- 23642367 chr4 115095426 115097426 Mesp1 Mesp1 is regarded as the master regulator of cardiovascular development, initiating the cardiac transcription factor cascade to direct the generation of cardiac mesoderm. mouse Low throughput Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner 否 -- embryonic stem cell E_02_0932 ChIP,EMSA Several Tal1 enhancers have been identified, but only the +40k enhancer region contains E-box motifs (Ogilvy et al., 2007), potential binding sites for Mesp1 (Figure 3B, left panel). Enhancer -- ChIP,EMSA Hpt,SCL/tal-1,Scl,bHLHa17,tal-1 -- -- -- Csx,Nkx-2.5,Nkx2.5,tinman RT-PCR -- -- Tal1 Nkx2-5 We performed ChIP in day 3 EBs after a prior 24 hr Mesp1 pulse and found that Mesp1 was enriched at this cis -regulatory element (Figure 3B, right panel) with a concurrent upregulation of Tal1 expression (Supplementary Figure S3B).We next performed electrophoretic mobility shift assays to confirm the direct interaction between Mesp1 and the Tal1 +40k Enhancer. At the protein level,the late pulse of Mesp1 elevated the expression of Nkx2.5,a cardiogenic transcription factor,and downstream markers,cTnT,cTnI and sarcomeric α-actinin. 23637611 chr11 69468873 69470873 CCND1 This release then enables the estrogen receptor to bind to the CCND1 promoter. human breast Low throughput TIP48/Reptin and H2A.Z requirement for initiating chromatin remodeling in estrogen-activated transcription Breast Tumor MCF-7 cell E_02_0933 ChIP,PCR,3C Long-range chromatin interactions between ERa recognition sequences and enhancers have been proposed to regulate ERa target genes in breast cancer cells. The main enhancer regulating CCND1 is located at the 39 end of the gene, 14 kb distant from the promoter. Enhancer 3C PCR BCL1,D11S287E,PRAD1,U21B31 -- -- -- ESA1,HTATIP,HTATIP1,PLIP,TIP,TIP60,ZC2HC5,cPLA2 ChIP -- -- CCND1 KAT5 The main Enhancer regulating CCND1 is located at the 3' end of the gene,14 kb distant from the promoter. TIP60 binding to the CCND1 promoter was analyzed by ChIP and shown as percent of input (n = 2). 23636943 chr11 72897942 72912333 P2RY2 These include an ERBS, which we refer to as ERBS1, located ;20 kb upstream of the promoter of the P2RY2 gene. human Low+High throughput Enhancer transcripts mark active estrogen receptor binding sites 否 -- MCF-7 cell E_02_0934 3C,ChIP-seq,ChIP-qPCR We integrated the data from our GRO-seq assays with data from a variety of other genomic assays (e.g., ChIP-seq, DNase-seq, ChIA-PET) using a novel computational pipeline to provide a comprehensive and global view of ESR1 enhancers and their regulation by E2 in MCF-7 cells. Together, our studies have shed new light on the activity of ESR1 at its enhancer sites and provide new insights about en_x0002_hancer function in general, including the potential roles of en_x0002_hancer transcription. Enhancer -- ChIP-seq,ChIP-qPCR HP2U,P2RU1,P2U,P2U1,P2UR,P2Y2,P2Y2R -- -- -- HNF3A,TCF3A 3C-PCR -- -- P2RY2 FOXA1 As shown in the GRO-seq browser tracks in Figure 1A, transcription of the P2RY2 gene and a region around ERBS1 is up-regulated rapidly in a short time course of treatment with 17b-estradiol.The transcripts from ERBS1(Fig. 1A), as well as ERBSs 2–5 (Supplemental Fig. 2), are produced bidirectionally from both strands of DNA,reminiscent of the enhancer RNAs (eRNAs) described previously (Kim et al. 2010), and the transcribed regions are associated with RNA Pol II and pre_x0002_viously identified transcription start sites (TSSs). 3C-PCR assay showing E2-induced looping between ERBS1 and the P2RY2 gene. The lowercase letters correspond to the primers denoted by orange arrows shown in panel A. The assays were conducted in the presence (experimental) or absence (control) of DNA ligase, as indicated. Digested and ligated bacterial artificial chromosome (BAC) DNA spanning the entire P2YR2 locus was used as a PCR control. 23631855 chr12 48369059 48369213 COL2A1 Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-β1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3. human Low throughput Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-β-Smad2/3 pathway in chondrocytic cells 否 -- SW 1353 E_02_0935 PCR,ChIP,Luciferase Reporter Assay In addition, CTS increased the association between Smad2/3 and the COL2A1 enhancer on chromatin in SW1353 cells (Fig. 3C). In stretched cells, DNA fragment that contained the COL2A1 enhancer was coimmunoprecipitated with Smad2/3, probably via complex for_x0002_mation among Smad2/3-SOX9-the SOX9-binding site, and was amplified by PCR using specific primers for the COL2A1 enhancer. Enhancer -- PCR,ChIP,Luciferase Reporter Assay ANFH,AOM,COL11A3,SEDC,STL1 -- -- -- CMD1,CMPD1,SRA1,SRXX2,SRXY10 Western blot,ChIP -- -- COL2A1 SOX9 Chromatin immunoprecipitation revealed that CTS increased Smad2/3 interaction with the CCN2 promoter and the COL2A1 enhancer. Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-β1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3. In Western blot(WB)analysis,CTS treatment(2h)did not influence total a mounts of endogenous Smad2/3 and SOX9 in each whole cell lysate(B,20 μg/lane). However,Smad2/3 detected in the nuclear fraction was increased by CTS(C,nucleus,20 μg/lane). In IP analys is using an anti-SOX9 antibody,CTS increased the association between phosphorylated Smad2/3 and SOX9 in the nuclear fraction derived from stretched SW1353 cells. 23598529 chr2 191834162 191834795 STAT1 In contrast, the transcriptional repressor REST binds to an RE-1 element in the STAT1 repressor region and in doing so represses transcription from the STAT1 gene regulatory region in melanoma cells lines. human Low throughput REST Negatively and ISGF3 Positively Regulate the Human STAT1 Gene in Melanoma 否 -- Mm96 E_02_0936 Luciferase Reporter Assay,ChIP,PCR Our previous analysis of the STAT1 gene recognized a region downstream of the promoter and enhancer regions strongly repressing transcription of luciferase gene repor_x0002_ters (20). In the present study, we define an RE-1 element within this repressor region, to which REST bound and repressed transcription. In the absence of REST, transcriptional repression of the STAT1 gene was dramatically reduced. Enhancer -- Luciferase Reporter Assay,ChIP,PCR CANDF7,IMD31A,IMD31B,IMD31C,ISGF-3,STAT91 -- -- -- -- -- -- -- STAT1 -- Analysis of REST and STAT1 expression levels in human melanoma cells showed that REST is commonly expressed in melanomas and, together with transcription_x0002_al activation and chromatin immunoprecipitation (ChIP) assay, shows that REST negatively regulates STAT1 expression, contributing to the nonresponsiveness of mel_x0002_anomas to IFN. -- 23307821 chr17 26829229 26831311 YY1 The overexpression of YY1 enhanced the cardiogenic differentiation of embryonic stem cells into CPCs. human Low throughput Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation 否 -- Cardiac progenitor cell E_02_0937 ChIP,PCR,Luciferase Reporter Assay,EMSA To examine in detail the potential binding of YY1 to Nkx2.5 enhancer, we performed an electromobility shift assay (EMSA) using the 2.1 kb cardiac enhancer located within -9435 and -7353 bases upstream from the murine NKX2.5 transcriptional start site.Binding of site #1 to YY1 was further confirmed using a DNA supershift assay (Figure 2C). To corroborate these in vitro data with their binding to the Nkx2.5 cardiac enhancer in vivo , we performed chromatin immunoprecipitation (ChIP) and PCR analysis using anti-YY1 antibodies on day 6 differentiated NK ESCs (Figure 2D), FACS-purified eGFP+ CPCs and eGFP- cells from day 6 differentiated NK ESCs (Figure 2E), and from embryonic day 9.5 hearts and body. Enhancer -- EMSA,ChIP,PCR Csx,Nkx-2.5,Nkx2.5,tinman YY1 regulates Nkx2.5 expression via a 2.1-kb cardiac-specific enhancer EMSA,ChIP,PCR To examine in detail the potential binding of YY1 to Nkx2.5 Enhancer, we performed an electromobility shift assay (EMSA) using the 2.1 kb cardiac Enhancer located within -9435 and -7353 bases upstream from the murine NKX2.5 transcriptional start site. NF-E1,YY-1 ChIP,Luciferase Reporter Assay,EMSA -- -- Nkx2-5 Yy1 To examine in detail the potential binding of YY1 to Nkx2.5 enhancer, we performed an electromobility shift assay (EMSA) using the 2.1 kb cardiac enhancer located within -9435 and -7353 bases upstream from the murine NKX2.5 transcriptional start site.Binding of site #1 to YY1 was further confirmed using a DNA supershift assay (Figure 2C). To corroborate these in vitro data with their binding to the Nkx2.5 cardiac enhancer in vivo , we performed chromatin immunoprecipitation (ChIP) and PCR analysis using anti-YY1 antibodies on day 6 differentiated NK ESCs (Figure 2D), FACS-purified eGFP+ CPCs and eGFP- cells from day 6 differentiated NK ESCs (Figure 2E), and from embryonic day 9.5 hearts and body. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis.To examine in detail the potential binding of YY1 to Nkx2.5 enhancer, we performed an electromobility shift assay (EMSA) using the 2.1 kb cardiac enhancer located within -9435 and -7353 bases upstream from the murine NKX2.5 transcriptional start site. 23302769 chr11 8301851 8303851 LMO1 Taken together, our results show that LMO1 is poised for expression in normal progenitors, where activation of SCL/TAL1 together with a breakdown of epigenetic repression of LMO1 regulatory elements induces ectopic LMO1 expression that contributes to the development and maintenance of T-ALL. Leukemia human Low throughput Bivalent promoter marks and a latent enhancer may prime the leukaemia oncogene LMO1 for ectopic expression in T-cell leukaemia 否 T-Cell leukemia T-acute lymphoblastic leukemia (T-ALL) E_02_0938 ChIP,RT-PCR,Luciferase Reporter Assay The LMO1 promoters display bivalent histone marks in multiple blood lineages including T-cells, and a 3’ flanking region at LMO1 ? 57 contains a transcriptional enhancer that is active in developing blood cells in transgenic mouse embryos. The LMO1 promoters become activated in T-ALL together with the 3’ enhancer, which is bound in primary T-ALL cells by SCL/TAL1 and GATA3. Enhancer -- ChIP,RT-PCR,Luciferase Reporter Assay RBTN1,RHOM1,TTG1 -- -- -- SCL,TCL5,bHLHa17,tal-1,HDR,HDRS ChIP,qPCR -- -- LMO1 TAL1,GATA3 To investigate whether lack of expres_x0002_sion in the haematopoietic system may be due to active repression of the two LMO1 promoters, we analysed ChIP-Sequencing data released to the public domain by the NIH Roadmap Epigeno_x0002_mics Mapping Project. ChIP assays on T-ALL cells from the same primagraft (X31) using antibodies against SCL/TAL1and GATA3. Analysis by quantitative PCR demonstrates significant binding of both SCL/TAL1 and GATA3 to the LMO1 +57 enhancer, with no binding to either of the two LMO1 promoters. 23159876 chr17 48258757 48260757 Col1a1 Our data show that overexpression of Runx2 and Osterix leads to a cooperative effect on the expression of the Col1a1 endogenous gene and its promoter reporter construct. mouse Low throughput Osterix induces Col1a1 gene expression through binding to Sp1 sites in the bone enhancer and proximal promoter regions 否 -- C2C12 cell E_02_0939 Luciferase Reporter Assay The Col1a1 promoter analysis showed the existence of two evolutionarily conserved regions containing pairs of Sp1 sites.These regions are located one at 1700 pb from the transcription start, known as bone enhancer(BE) and where the regulation of Col1a1 expression by Osx has been described,and another region located in the proximal promoter region. Enhancer -- Luciferase Reporter Assay,PCR EDSARTH1,EDSC,OI1,OI2,OI3,OI4 -- -- -- AML3,CBF-alpha-1,CBFA1,CCD,CCD1,CLCD,OSF-2,OSF2,PEA2aA,PEBP2aA Luciferase Reporter Assay -- -- COL1A1 RUNX2 To further confirm the relevance of p38 in the regu_x0002_lation of Col1a1 by Osx, we studied the effect of a constitutive active form of MKK6, the MAPKK activating p38, combined with Osx on the ac_x0002_tivation of Col1a1 promoter by Osx. The overexpression of Osx or MKK6 activated both the full-length (?2483pCol1a1) as well the proximal promoter reporter constructs. Moreover, expression of Osx and MKK6 together had an additive effect on the activation of both reporter constructs. Induction of long Osx transcriptional activity by Runx2. C2C12 cells were co-transfected with mock, short or long Osx constructs and/or Runx2 construct overnight, and serum-starved for 24 h. Luciferase activity was measured and normalized against β-galactosidase activity. 23108396 chr11 69468761 69470761 CCND1 These results suggest that release of a histone H2A.Z-mediated repression loop activates CCND1 for transcription. human breast Low+High throughput H2A.Z-dependent crosstalk between enhancer and promoter regulates cyclin D1 expression -- MDA-MB-23,MDA-MB-436 E_02_0940 3C,ChIP,qPCR ChIP confirmed that H2A.Z siRNA treatment lead to markedly reduced binding of H2A.Z to the CCND1 TSS. Concomitant to increased mRNA levels, polymerase II (pol II) recruitment to the CCND1 TSS slightly increased. Enhancer 3C qPCR BCL1,D11S287E,PRAD1,U21B31 The enh2 has an active role in ER-independent CCND1 activation. ChIP In addition, CCND1 activation in siH2AZ-transfected MDA-MB231 cells was accompanied by a strong recruitment of pol II to enh2 (Figure 1c, right panel), as described previously for E2 stimulated MCF-7 cells. We conclude that enh2 has an active role in ER-independent CCND1 activation. -- -- -- -- CCND1 -- We conclude that enh2 has an active role in ER-independent CCND1 activation.To investigate whether the CCND1 TSS interacts with enh2, we used a chromatin conformation capture (3C) assay,which detects physical proximity between distal DNA sites by ligation of cross-linked restricted DNA fragments. -- 23024062 chr1 60908875 60908895 CTLA4 Together, these data suggest that cAMP may negatively regulate pulmonary inflammatory responses in vivo and in vitro by altering CTLA4 expression. human Low throughput Regulation of cytotoxic T lymphocyte antigen 4 by cyclic AMP 否 -- T cell E_02_0941 Luciferase Reporter Assay T cells were stimulated with CPT after transfection of CTLA4 luciferase reporter constructs (including -1221, -343, -238, -167, and-63 bp relative to the CTLA4 transcription start site). suggesting the presence of an enhancer binding site in this region. Enhancer -- ChIP Cd152,Ctla-4,Ly-56 -- -- -- 2310001E10Rik,3526402H21Rik,AV083133,Creb,Creb-1 ChIP -- -- Ctla4 Creb1 The promoter region from 2150 to 2130 bp contains a putative CREB binding site, a well known downstream transcription factor of cAMP signaling. To define whether the putative CREB binding site (2150 to 2143 bp) is responsive to cAMP, we performed ChIP assay with CREB antibody in T cells, with or without CPT treatment. The promoter region from -150 to -130 bp contains a putative CREB binding site, a well known downstream transcription factor of cAMP signaling. 22877652 chr14 67743318 67743610 AR We conclude that AR repression of GnRH-E1 acts via multiple AR_x0002_responsive regions, including the site at _x0002_1792/_x0002_1791. human Low throughput Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1 否 Polycystic Ovarian Syndrome GT1–7 cell E_02_0942 ChIP,PCR,Luciferase Reporter Assay,EMSA To determine whether AR interacts with endogenous chromatin in the GnRH-E1 region in GT1-7 cells, ChIP assays were performed. GT1-7 cells were transiently transfected with luciferase reporter constructs containing the GnRH-P (P), GnRH-E1 (E1), and/or GnRH-E2 (E2) regions, and/or the RSV promoter (RSVp) or enhancer (RSVe), as indicated, along with the AR expression vector. Enhancer -- Luciferase Reporter Assay Gnrh,Gnrh2,LHRH,Lhrh1,Lnrh,hpg AR represses GnRH transcription via the major Enhancer (GnRH-E1). ChIP For the rest of this study, we chose to evaluate the mechanism of repression by AR using GnRH-E1 upstream of RSVp to avoid com_x005f_x0002_pensation by the androgen-responsive GnRH promoter.To determine whether AR interacts with endogenous chromatin in the GnRH-E1 region in GT1-7 cells,ChIP assays were performed. 2810482H01Rik,NF-A1,Oct-1,Oct1,Otf-1,Otf1,Gata-4,D17Wsu76e,PREP1,AV026640,Nkx2.1,T/EBP,Titf1,Ttf-1 EMSA,PCR -- -- Gnrh1 Oct1,Pbx,Nkx2-1 AR associates with the enhancer 1 region of the GnRH regulatory region and represses transcription.GT1-7 cells were transiently transfected with luciferase reporter constructs containing the GnRH-P (P), GnRH-E1 (E1),and/or GnRH-E2 (E2) regions, and/or the RSV promoter (RSVp) or enhancer (RSVe), as indicated, along with the AR expression vector. AR bound to the -1796/-1791 sequence in electrophoretic mobility shift assays, indicating a direct interaction with DNA or other transcription factors in this region. 22771493 chr8 124323890 124325890 ATAD2 ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. human Low throughput Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells 否 Prostate Cancer LNCaP E_02_0943 qPCR,Luciferase Reporter Assay,ChIP,EMSA,3C Taken together, these data demonstrate that the poten_x0002_tial ARBS identified within the distal enhancer region of ATAD2 gene indeed interacts strongly and specifically with AR in vitro and suggest that it could be a good candidate as a functional ARBS in vivo.To ascertain whether the ARBS identified within the ATAD2 enhancer region is functional in cells in vivo, we performed ChIP using formaldehyde cross-linked LNCaP cells. Enhancer -- ChIP,EMSA,RT-qPCR ANCCA,CT137,PRO2000 -- -- -- AIS8, DHTR, HUMARA, HYSP1, KD, NR3C4, SBMA, SMAX1, TFM,E2F-1,RBAP1,RBBP3,RBP3 EMSA -- -- ATAD2 AR,E2F1 In addition, we analyzed chromatin immunoprecipita_x0002_tion (ChIP)-seq data from the literature to identify genes that might share the same regulation mechanism as ATAD2.With this in mind, we aimed first at checking whether ATAD2 might be a direct target gene of AR. To test this hypothesis, we analyzed ATAD2 gene response to androgens in LNCaP cells in the presence of cycloheximide (CHX), a protein synthesis inhibitor. To check the binding of AR to this putative ARBS, we first performed EMSA experiments with bacterially produced AR-DNA-binding domain (DBD) purified to homogeneity,siE2F1 and siAR transfection showed the very efficient and specific knockdown of E2F1 and AR, respectively, at both mRNA and protein levels. 22761896 chr14 67741735 67744661 Gnrh1 HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. mouse Low throughput Histone deacetylases regulate gonadotropin-releasing hormone I gene expression via modulating Otx2-driven transcriptional activity 否 -- GT1–7 cell E_02_0944 Luciferase Reporter Assay,ChIP,PCR the luciferase activities in GT1–7 cells were noticeably decreased without HDACIs treatments, suggesting that potential enhancer elements located in the regions (-3446,-2087 bp and -1134,-520 bp). Enhancer -- Western blot,Immunofluorescence,ChIP,EMSA Gnrh,Gnrh2,LHRH,Lhrh1,Lnrh,hpg -- -- -- E130306E05Rik ChIP,EMSA -- -- Gnrh1 Otx2 The Otx2 protein levels were also obviously reduced in GT1–7 cells showed by western blot analysis (Figure 5B) and immunofluorescence staining (Figure 5C).The results of ChIP assay showed that the binding ability of Otx2 to neuron-specific elements (2356,2249 bp) in Gnrh1 promoter obviously decreased after HDACIs treatments (Figure 6B).To further analyze the affinities of Otx2 to the two conserved binding sites in mouse Gnrh1 promoter respectively, EMSA was performed with probes containing the 2268,2239 bp and 2330,2301 bp sequences [20](Figure 6C, above). Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. 22728936 chr9 119469800 119469811 Tbx5 Our results establish a direct molecular link between Tbx5 and Scn5a and elucidate a hierarchy between human GWAS loci that affects function of the mature VCS, establishing a paradigm for understanding the molecular pathology of CCS disease. mouse Low+High throughput TBX5 drives Scn5a expression to regulate cardiac conduction system function 否 Cardiac Conduction System Disease HL-1 cells E_02_0945 Luciferase Reporter Assay,ChIP-seq We tested the ability of this putative enhancer to activate transcription in a TBX5-dependent manner. TBX5 dramatically upregulated enhancer-dependent luciferase reporter expression from this genomic region (chr9:119,378,051–119,379,479;NCBI build 37/mm9) in vitro (Figure 6B). Enhancer -- Luciferase Reporter Assay Nav1.5,Nav1.5c,SkM1,SkM2,mH1 TBX5-responsive Enhancer downstream of Scn5a sufficient to drive VCS expression in vivo, dependent on canonical T-box binding sites. ChIP-seq Here, we found a direct molecular link between TBX5 and Scn5a via a TBX5-respon_x005f_x0002_sive downstream Enhancer that was sufficient to direct VCS-specif-ic gene expression. Our results identified a TBX5-Scn5a molecular network essential for function of the mature VCS. Tbx5 ChIP-seq -- -- Scn5a,Scn5a Tbx5,Tbx5 We tested the ability of this putative enhancer to activate transcription in a TBX5-dependent manner. TBX5 dramatically upregulated enhancer-dependent luciferase reporter expression from this genomic region (chr9:119,378,051–119,379,479;NCBI build 37/mm9) in vitro (Figure 6B). ;We tested the ability of this putative enhancer to activate transcription in a TBX5-dependent manner. TBX5 dramatically upregulated enhancer-dependent luciferase reporter expression from this genomic region (chr9:119,378,051–119,379,479;NCBI build 37/mm9) in vitro (Figure 6B). We bioinformatically interrogated the Scn5a locus to identify potential TBX5-responsive Enhancers using the overlap of 4 independent data sets: (a) evolutionary conservation (21);(b) ChIP-seq studies identifying TBX5 binding sites in the atrial cardiomyocyte HL-1 cell line.;We bioinformatically interrogated the Scn5a locus to identify potential TBX5-responsive Enhancers using the overlap of 4 independent data sets: (a) evolutionary conservation (21);(b) ChIP-seq studies identifying TBX5 binding sites in the atrial cardiomyocyte HL-1 cell line. 22701669 chr14 47056226 47056692 Bmp4 These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium. mouse Low throughput An evolutionarily conserved enhancer regulates Bmp4 expression in developing incisor and limb bud 否 -- LS-8 cell E_02_0946 EMSA,Phylogenetic Footprinting In vitro electrophoretic mobility shift assays (EMSA) and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Enhancer -- ChIP,PCR Bmp-4,Bmp2b,Bmp2b-1,Bmp2b1 Pitx2 ChIP demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. ChIP,PCR,qPCR Using primers that target the Pitx1/2 binding motif in the 396 bp Bmp4 Enhancer sequence (CONS3.8), DNA purified from crosslinked LS8 chromatin after immunoprecipitation with an anti-Pitx2 antibody yielded a 4.7-fold increase in amplicon abundance, relative to an IgG control, by PCR and qPCR. 9430085M16Rik,Brx1,Brx1b,Munc30,Otlx2,Ptx2,Rieg EMSA,ChIP -- -- Bmp4 Pitx2 Pitx2 chromatin immunoprecipitation (ChIP) demonstrate direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line.Using primers that target the Pitx1/2 binding motif in the 396 bp Bmp4 enhancer sequence (CONS3.8), DNA purified from crosslinked LS8 chromatin after immunoprecipitation with an anti-Pitx2 antibody yielded a 4.7-fold increase in amplicon abundance, relative to an IgG control, by PCR and qPCR (Figure 6A, B). Electrophoretic Mobility Shift Assay (EMSA) exhibits robust binding of Pitx1 protein to both a positive control bicoid DNA sequence and to the consensus Pitx1/2 binding site in with a 25 probe sequence in the CONS3.8 sequenceTo determine whether Pitx2 physically binds the CONS3.8 Bmp4 Enhancer in living cells,we performed Chromatin Immunoprecipitation (ChIP) assays in LS8 mouse dental epithelial cells. 22665440 chr17 69107686 69108045 SOX9 Together, our results demonstrate that multiple genetic variants mapping to a unique enhancer looping to the SOX9 oncogene can account for the risk associated with the PCa 17q24.3 locus. human Low throughput Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus 是 rs8072254 -- LNCaP E_02_0947 Luciferase Reporter Assay,ChIP,3C-qPCR,ChIP-qPCR To determine if the rs1859962 PCa risk LD block harbors enhancers, we examined the H3K4me1 ge_x0002_nome-wide distribution defined by ChIP-seq assays in LNCaP and VCaP PCa cells.We show that there are five enhancers within the target genomic segment, hereafter referred to as E1–E5. Enhancer -- qPCR CMD1,CMPD1,SRA1,SRXX2,SRXY10 -- -- -- AIS8, DHTR, HUMARA, HYSP1, KD, NR3C4, SBMA, SMAX1,TFM,HNF3A,TCF3A ChIP,Luciferase Reporter Assay 69107816 Luciferase Reporter Assay,ChIP SOX9 AR,FOXA1 This chromatin loop was confirmed through TaqMan probe–based qPCR assays with a probe targeting the SOX9 gene (Fig. 2C). The chromatin interaction was further confirmed by sequencing the PCR product (Supplemental Fig. S7). Further_x0002_more, this chromatin loop appears to be specific to SOX9, because no other loop could be detected between E1 and any other genes(MAP2K6, KCNJ16, KCNJ2) found within this ;3-Mb window. In agreement, the luciferase assay in LNCaP cells depletedor not of AR using siRNA reveals that AR is required for the increased transcriptional response associated with the rs8072254 variant A allele.The FKH PWM, defined based on thousands of FOXA1 binding sites identified by ChIP-seq assays, reveals that the tenth position is invariably an A residue. 22645302 chr12 8036824 8048824 KDM3A KDM3A is recruited to the SLC2A3 locus in an HIF1-dependent manner and demethylates H3K9me2 so as to upregulate its expression. human Low+High throughput Dynamic Change of Chromatin Conformation in Response to Hypoxia Enhances the Expression of GLUT3 (SLC2A3) by Cooperative Interaction of Hypoxia-Inducible Factor 1 and KDM3A 否 -- HEK-293,HeLa E_02_0948 ChIP-PCR,RT-PCR,3C-ChIP,ChIP-seq To examine whether histone enhancers mark changes under hypoxia, we compared the HIF1 binding sites and H3K27ac under normoxia and hypoxia on a genome-wide scale. The number of total reads and uniquely mapped sequences of the ChIP-seq for histone marks are shown in Table S4 in the supplemental material. H3K27ac sites overlapped at 12,498 sites between the state of normoxia (14,679 sites) and hypoxia (16,366 sites) on a genome-wide scale.The results of the HIF1 ChIP-seq analysis provided data of hypoxic enhancer 2 (kbp -24 from the TSS) at the SLC2A3 loci. Enhancer 3C ChIP-PCR,ChIP GLUT3 The enhancer 2 was functionally active under hypoxic condition ChIP-PCR,Luciferase Reporter Assay The experimental data described above showed that distal enhancer 2 was functionally active under hypoxic conditions, suggesting that enhancer 2 has an especially close proximity to the promoter of SLC2A3 under hypoxic conditions. HIF-1-alpha,HIF-1A,HIF-1alpha,HIF1,HIF1-ALPHA,MOP1,PASD8,bHLHe78 ChIP -- -- SLC2A3 HIF1A We elucidated that both the chromatin conformational structure and histone modification change under hy_x0002_poxic conditions and enhance the expression of SLC2A3 based on the combined results of chromatin conformation capture (3C) and ChIP assays. KDM3A is recruited to the SLC2A3 locus in an HIF1-dependent manner and demethylates H3K9me2 so as to upregulate its expression.These findings provide novel insights into the interaction between HIF1 and KDM3A and also the epigenetic regulation of HIF1. Genome-wide analysis of HIF1 binding sites (chromatin immunoprecipitation[ChIP] with deep sequencing) of endothelial cells clarified that HIF1 mainly binds to the intergenic regions distal from tran_x0002_scriptional starting sites under both normoxia and hypoxia. 22543974 chr12 114463712 114464080 TBX5 We uncovered three enhancers that collectively recapitulate the endogenous expression pattern of TBX5 in the developing heart. human heart Low+High throughput Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease Congenital Heart Disease HeLa,T cell E_02_0949 EMSA,PCR,ChIP-seq This strategy considered multiple genome-wide ChIP-seq data sets including the enhancer associated transcriptional co-activator p300, cardiac transcription factors Mef2a, TBX5, Gata4, Nkx2.5, SRF and computationally predicted enhancers, as well as the enhancer-associated histonemodificationH3K4me1and evolutionary conservation to identify and prioritize likely functional non-coding regions. Enhancer -- EMSA,PCR HOS A significant number of CHD associated with TBX5 dysfunction might arise from non-coding mutations in TBX5 heart enhancers, effectively decoupling the heart and hand phenotypes of the Holt-Oram syndrome. EMSA,ChIP-seq Notably, all lines exhibited weak expression in the left atrium and almost no ex_x0002_pression in the right atrium, suggesting that the bulk of TBX5 atrial expression is regulated by Enhancers outside the genomic region covered by this BAC. HOS EMSA -- -- TBX5,TBX5 TBX5,TBX5 We identified three elements (CREs 2, 9, 16) with patterns of Enhancer activity overlapping the endogenous expression pattern of TBX5 and the Enhancer-trap BACs in which they were contained.;We identified three elements (CREs 2, 9, 16) with patterns of Enhancer activity overlapping the endogenous expression pattern of TBX5 and the Enhancer-trap BACs in which they were contained. We hypothesized that the variant nucleotide disrupts transcrip_x0002_tion factor binding to Enhancer 9. To test this, we performed an electrophoretic mobility shift assay using short DNA probes spanning either the wild-type (G) or variant (T) allele.;We hypothesized that the variant nucleotide disrupts transcrip_x0002_tion factor binding to Enhancer 9. To test this, we performed an electrophoretic mobility shift assay using short DNA probes spanning either the wild-type (G) or variant (T) allele. 22383952 chr17 42078865 42079198 NAGS The presented data strongly suggest that Sp1, CREB, HNF-1, and NF-Y, that are known to be responsive to hormones and diet, regulate NAGS transcription. human Low throughput Transcriptional Regulation of N-AcetylglutamateSynthase 否 -- Hep G2 cell E_02_0950 PCR,ChIP,Luciferase Reporter Assay Reporter assays to compare the effect of the enhancer in liver,intestine and lung cells, included data that were normalized to the reporter expression driven by the NAGS promoter. While the NAGS enhancer (4.10PromEnh) increased expression of the reporter gene by 50% in liver derived cells (Figure 2A), expression of the luciferase gene did not increase in the intestine or lung derived cells (Figure 8) suggesting that the enhancer may determine tissue specificity of NAGS expression. Enhancer -- ChIP,Luciferase Reporter Assay AGAS,ARGA Two regions of high conservation upstream of the translation start of the NAGS gene. Reporter assays confirmed that these regions represent promoter and enhancer and that the enhancer is tissue specific. Luciferase Reporter Assay Reporter assays to compare the effect of the enhancer in liver, intestine and lung cells, included data that were normalized to the reporter expression driven by the NAGS promoter. While the NAGS enhancer (4.10PromEnh) increased expression of the reporter gene by 50% in liver derived cells (Figure 2A), expression of the luciferase gene did not increase in the intestine or lung derived cells (Figure 8) suggesting that the enhancer may determine tissue specificity of NAGS expression. When HNF-1 SP1,HNF-1A,HNF1,HNF4A,IDDM20,LFB1,MODY3,TCF-1,TCF1,CBF-A, CBF-B,HAP2,NF-YA ChIP,qPCR -- -- NAGS SP1,HNF1A,NF-Y We subsequently confirmed that these regions function as promoter and enhancer and that the enhancer is most effective in liver cells. Avidin-agarose protein_x0002_DNA pull-down assays have been used to confirm binding of Sp1 and CREB within the NAGS promoter and Hepatic Nuclear Factor 1 (HNF-1) and NF-Y within the enhancer regions. Chromatin immunoprecipitation (ChIP) and quantitative real_x0002_time PCR have been used to independently verify that Sp1 and CREB bind to the promoter region, and HNF-1 and NF-Y bind to the enhancer region. We also used 59RACE analysis to identify multiple transcription start sites for NAGS that may be species and tissue specific. Thus,Pull-down and ChIP assays confirmed that Sp1 and CREB bind along the NAGS promoter and HNF-1 and NF-Y bind along the Enhancer. 22378757 chr10 62128342 62130342 NEUROG3 Collectively, these results establish a mechanism by which activation of STAT3 regulates the expression of NEUROG3 to subsequently drive differentiation of SSC and progenitor spermatogonia in the mammalian germline. human Low throughput NEUROG3 is a critical downstream effector for STAT3-regulated differentiation of mammalian stem and progenitor spermatogonia 否 -- germ line cell E_02_0951 ChIP,PCR,Luciferase Reporter Assay To investigate this further, we used a ChIP method to determine whether STAT3 binds Neurog3 regulatory elements in THY1+ spermatogonia. PCR analysis with primers designed to span a 200-bp segment of the Neurog3 distal promoter/enhancer region including the STAT3 binding site produced an amplicon of expected size; Enhancer -- Luciferase Reporter Assay,Transfection Atoh5,Math4B,bHLHa7,ngn3 -- -- -- 1110034C02Rik,AW109958,Aprf ChIP -- -- Neurog3,Neurog3 Stat3,Stat3 Next, we determined whether STAT3 directly regulates Neurog3 promoter/enhancer activity. To investigate this, we used a reporter construct in which the Neurog3 promoter/enhancer sequence was cloned upstream of the firefly luciferase gene, termed pNeurog3-Luc.The transfection efficiency of cultured SSC/progenitor spermatogonia with plasmid DNA vectors is low, thus HeLa cells were used with the reporter vector to determine whether STAT3 is capable of stimulating Neurog3 promoter/enhancer activity.;Next, we determined whether STAT3 directly regulates Neurog3 promoter/enhancer activity. To investigate this, we used a reporter construct in which the Neurog3 promoter/enhancer sequence was cloned upstream of the firefly luciferase gene, termed pNeurog3-Luc.The transfection efficiency of cultured SSC/progenitor spermatogonia with plasmid DNA vectors is low, thus HeLa cells were used with the reporter vector to determine whether STAT3 is capable of stimulating Neurog3 promoter/enhancer activity. Moreover,using a ChIP approach we found that STAT3 physically interacts with the distal Neurog3 promoter/Enhancer in THY1 undifferentiated spermatogonia and using a reporter construct show that STAT3 regulates transcription through this promoter.;Moreover,using a ChIP approach we found that STAT3 physically interacts with the distal Neurog3 promoter/Enhancer in THY1 undifferentiated spermatogonia and using a reporter construct show that STAT3 regulates transcription through this promoter. 22303449 chr5 44385749 44386845 ISL1 ISL1 transcription demarcated an anatomical region supporting the conserved existence of a SHF in humans, and transcription factors of the GATA family were co-expressed therein. human Low throughput ISL1 Directly Regulates FGF10 Transcription during Human Cardiac Outflow Formation 否 -- embryonic cell E_02_0952 ChIP,EMSA In conjunction, we identified a novel enhancer containing a highly conserved ISL1 consensus binding site within the FGF10 first intron. ChIP and EMSA demonstrated its direct occupation by ISL1. Transcription mediated by ISL1 from this FGF10 intronic element was enhanced by the presence of GATA4 and TBX20 cardiac transcription factors. Finally, transgenic mice confirmed that endogenous factors bound the human FGF10 intronic enhancer to drive reporter expression in the developing cardiac outflow tract. Enhancer -- ChIP,EMSA FGF10 Endogenous factors bound the human FGF10 intronic enhancer to drive reporter expression in the developing cardiac outflow tract. ChIP,EMSA,Transgenic mice Finally, transgenic mice confirmed that endogenous factors bound the human FGF10 intronic enhancer to drive reporter expression in the developing cardiac outflow tract. ISLET1,Isl-1,ASD2,TACHD,TOF,VSD1,ASD4 ChIP,EMSA -- -- FGF10 ISL1,GATA4,TBX20 Using chromatin immunoprecipitation (ChIP) of microdissected embryonic human hearts, we demonstrated that at Carnegie stages 14–15 (33–36 dpf), ISL1 bound to and enriched a 327 bp FGF10-Int1 fragment (Fig. 2A). In contrast, ISL1 did not occupy FGF10-Pr1 or FGF10-Pr2. Acetylated histone H4 did bind both the ISL1 and FGF10 promoters at CS14-15, confirming that the chromatin around these two promoters is transcriptionally active in the human heart at these stages. ChIP and EMSA demonstrated its direct occupation by ISL1. Transcription mediated by ISL1 from this FGF10 intronic element was enhanced by the presence of GATA4 and TBX20 cardiac transcription factors. 22265404 chr14 90847327 90849327 IRS1 IRS1 is known to participate in type-2 diabetes (T2D) mellitus, and is found specifically expressed in MCF7 cells (Figure 7D). human Low+High throughput Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation 否 Congenital Limb Deformity MCF-7,K-562,HeLa,HCT 116,Nb4 E_02_0953 3C-qPCR,Luciferase Reporter Assay,ChIP-seq To examine potential enhancer activity of promoters, we per_x0002_formed luciferase reporter gene assays, a commonly used method for promoter and enhancer characterization. Enhancer 3C-qPCR Luciferase Reporter Assay CALML2,CAM2,CAM3,CAMB,CAMC,CAMI,CAMIII,CPVT4,DD132,LQT14,PHKD,caM -- -- -- -- -- -- -- CALM1 -- In another example (Figure 5F), the promoter of CALM1 interacts with an enhancer element 15 kb upstream and connects to the promoter of C14orf102 further upstream in 65kb. Both RNA-Seq data and the H3K4me3/me1 log ratio indi_x0002_cated that the CALM1 promoter was strong, whereas the C14orf102 promoter was weak and enhancer-like. The luciferase reporter gene assay showed marginal enhancement to the CALM1 promoter reporter gene activity by the native CALM1 enhancer and the C14orf102 promoter individually. -- 22264824 chr11 32244715 32246895 Nprl3 A substantial proportion of the expression of Nprl3 mRNA seen in erythroid cells is derived from an erythroid-specific alternative promoter(s) distinct from the canonical Nprl3 promoter. mouse Low+High throughput Intragenic enhancers act as alternative promoters 否 -- Primary Erythroid Cell E_02_0954 RT-PCR,ChIP,ChIP-seq Beyond this AFE the isoform structure appears identical to the full-length transcript. Interestingly, the AFE coincides with one of the known intragenic enhancers.First, we tested wild-type mouse tissues by RT-PCR to verify the existence of this alternative transcript. Enhancer -- RT-PCR,ChIP,ChIP-seq Aag,CGTHBA,HS-26,HS-40,Mare,Phg,Prox1,m(alpha)RE Intragenic Enhancers frequently act as alternative tissue_x005f_x0002_specific promoters producing a class of abundant,spliced, multiexonic poly(A)+ RNAs (meRNAs) which reflect the host gene’s structure. ChIP,RT-PCR,ChIP-seq To address this problem, we analyzed transcrip_x005f_x0002_tion of the Nprl3 gene after deleting its constitutive promoter. This revealed that intragenic Enhancers act as highly active, alternative tissue-specific promoters for the gene containing them. -- -- -- -- Nprl3 -- Beyond this AFE the isoform structure appears identical to the full-length transcript. Interestingly, the AFE coincides with one of the known intragenic enhancers.First, we tested wild-type mouse tissues by RT-PCR to verify the existence of this alternative transcript. -- 22212979 chr19 51354804 51355203 TMPRSS2 Upon stimulation with 1 nM DHT, AR and RNA Pol II were recruited onto PSA and TMPRSS2 enhancer regions to a greater extent (P < 0.05) in AR-overexpressing cells compared to control cells. human Low throughput Androgen Receptor Overexpression Alters Binding Dynamics of the Receptor to Chromatin and Chromatin Structure 否 -- LNCaP E_02_0955 qRT-PCR,ChIP Chromatin immunoprecipitation (ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine(TMPRSS2) genes was performed.For PSA, in addition to the AREs located 131 and 150 bp from the tran_x0002_scription start site (TSS), an enhancer region 4 kb upstream of the TSS has been documented.For the TMPRSS2 gene, the AREs in the regulatory region are located 13.5 kb [27,38] and 700 bp up_x0002_stream of the TSS. Enhancer -- ChIP-qPCR,ChIP APS,KLK2A1,PSA,hK3 -- -- -- AIS8,DHTR,HUMARA,HYSP1,KD,NR3C4,SBMA,SMAX1,TFM ChIP-qPCR -- -- KLK3 AR Chromatin immunoprecipitation(ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine 2(TMPRSS2) genes was performed. qRT-PCR was used to measure the levels of PSA and TMPRSS2 transcripts.We performed ChIP-qPCR analyses on these selected genomic sites of PSA and TMPRSS2. At the 1 hr time point, AR loading onto the TMPRSS2 enhancer (Fig. 3A) was already significantly (P < 0.001, t-test) higher in LNCaP-ARhi cells than in the control cells. However, the TMPRSS2 promoter did not significantly recruit AR, at least in the 4 hr time (Fig. 3B).ChIP-qPCR was performed to assess the AR loading. 22072553 chr1 38469166 38512500 Hoxa9 Hoxa9 regulates transcription by interacting with enhancers of genes important for hematopoiesis and leukemia. mouse Low throughput Identification and characterization of Hoxa9 binding sites in hematopoietic cells 否 Acute Leukemia BM Cell E_02_0956 Transfection,ChIP-chip,Luciferase Reporter Assay Furthermore, a subset of these sites shows enhancer activity in transient transfection assays. ChIP-chip data were analyzed with MA2C 36 and a customized R package.These studies showed that H3 and H4 acetylation and p300/CBP binding is centered on the H/M peaks and is flanked by regions of histone H3K4me1 in a bimodal distribution characteristic of enhancer sequences (Figure 3B). 3To test for potential enhancer (or repressor activity), 22 Hoxa9/Meis1 binding sites as well as 2 control regions randomly selected in the genome where there is no Hoxa9/Meis1 binding were cloned as ~1000-bp fragments. These were inserted into the multiple cloning site of the pTAL-Lucvector,electroporated into myeloblastic K562 cells and were analyzed by Dual Luciferase Reporter Assays (Promega; supplemental Figure 3). Enhancer -- Luciferase Reporter Assay 3222402O04Rik,A730046J16,LAF-4,Laf4 -- -- -- D6a9,Hox-1.7,C530044H18Rik,Evi8 ChIP-qPCR -- -- Aff3 Hoxa9,Meis1 To test for potential enhancer (or repressor activity), 22 Hoxa9/Meis1 binding sites as well as 2 control regions randomly selected in the genome where there is no Hoxa9/Meis1 binding were cloned as ~1000-bp fragments. These were inserted into the multiple cloning site of the pTAL-Lucvector,electroporated into myeloblas- tic K562 cells and were analyzed by Dual Luciferase Reporter Assays (Promega; supplemental Figure 3). Confirmation of selected Hoxa9 and Meis1 binding sites by ChIP and quantitative PCR. 21868451 chr5 134350424 134352424 PITX1 Here, we report that expression of paired-like homeodomain transcription factor (PITX1), a tumor suppressor and member of the homeobox family of tran_x005f_x0002_scription factors, is robustly up-regulated by E2 in several ER_x0001_ -positive breast cancer cell lines via ER_x0001_ -dependent interaction between the proximal promoter and an enhancer region 5_x0001_ upstream of the PITX1 gene. human Low throughput The Estrogen-Regulated Transcription Factor PITX1 Coordinates Gene-Specific Regulation by Estrogen Receptor-Alpha in Breast Cancer Cells 否 -- MCF-7 cell E_02_0957 ChIP,Luciferase Reporter Assay,3C Genetic locus from the UCSC genome browser showing the natural 5 to 3 orientation of the PITX1 gene with the location of the identified ER binding regions, the proximal promoter and enhancer, and the location of the primers used in ChIP and chromosome conformation capture experiments. Enhancer -- Luciferase Reporter Assay,Transfection BFT,CCF,LBNBG,POTX,PTX1 -- -- -- ER,ESR,ESRA,ESTRR,Era,NR3A1 ChIP -- -- PITX1 ESR1 ER regulation of PITX1 involves interaction of the ER-binding distal enhancer with the promoter of the PITX1 gene via intrachromosomal looping.We next determined whether the PITX1 enhancer and promoter regions were estrogen responsive by cloning these regions from genomic DNA into luciferase reporters, and we conducted transient transfection assays. Recruitment,monitored by ChIP,of ER and PITX1 to ER binding sites that contain a consensus PITX1 binding site in vehicle and 10 nM E2-treated 231ER cell at 45 min (panel D) or to ER binding sites that lack a consensus PITX1 binding site in vehicle and 10 nM E2-treated 231ER cell at 45 min. 21822303 chr3 34646162 34646551 Sox2 These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation. mouse Low throughput Sox2 expression in breast tumours and activation in breast cancer stem cells 否 -- MCF-7 cell E_02_0958 Luciferase Reporter Assay We transfected MCF7 and T47D cells with luciferase reporter vectors for the upstream distal enhancer and the core promoter to test whether induction of Sox2 protein was achieved through transcriptional activation of Sox2 promoter. Enhancer -- Luciferase Reporter Assay Sox-2,lcc,ysb -- -- -- -- -- -- -- Sox2 -- We transfected MCF7 and T47D cells with luciferase reporter vectors for the upstream distal enhancer and the core promoter to test whether induction of Sox2 protein was achieved through transcriptional activation of Sox2 promoter. -- 21798992 chr8 117978845 117979466 SLC30A8 Genome-wide association studies have shown that a polymorphic variant in SLC30A8, which encodes zinc transporter-8, is associated with altered susceptibility to type 2 diabetes (T2D). human Low throughput Characterization of the human SLC30A8 promoter and intronic enhancer. 否 rs62510556 Type 2 Diabetes Mellitus βTC-3,αTC-6 E_02_0959 Luciferase Reporter Assay,PCR,Transfection we have identified a conserved islet beta cell-specific enhancer in SLC30A8 intron 2 (Figs. 4 & 5). Enhancer -- Luciferase Reporter Assay,PCR,Transfection ZNT8,ZnT-8 -- -- -- -- -- 118164272 Luciferase Reporter Assay,PCR SLC30A8,SLC30A8 --,-- To determine whether the +16579 and +16954 region of intron 2 in the human SLC30A8 gene also represents a transcriptional enhancer, this region was isolated using PCR and ligated 5' of the ?150/+3 G6PC2-luciferase fusion gene described above. Luciferase expression directed by this fusion gene was then analyzed by transient transfection of βTC-3 and αTC-6 cells.;To determine whether the +16579 and +16954 region of intron 2 in the human SLC30A8 gene also represents a transcriptional enhancer, this region was isolated using PCR and ligated 5' of the ?150/+3 G6PC2-luciferase fusion gene described above. Luciferase expression directed by this fusion gene was then analyzed by transient transfection of βTC-3 and αTC-6 cells. --;-- 21797989 chr7 19409838 19410044 MR1 In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1’s positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types. human Low throughput Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer. 否 -- MM14 E_02_0960 EMSA,Immunofluorescence,ChIP Of particular interest was a 95-bp region (+901 to +995) that was subsequently proven to exhibit the properties of a transcriptional enhancer (Figure 1). Enhancer -- ChIP CPK-Mm,M-CK,MCK,?Ckm -- -- -- 5430401D19Rik,9930028G15Rik,AV011172,Mef2 ChIP-seq -- -- Ckm Mef2 The chromatin immunoprecipitation (ChIP) primer pairs (black lines) that span the 5’-enhancer sequence were used as positive controls for MyoD and myogenin binding to functional E-boxes. MEF2 ChIP-seq occupancy at the 6.5- MCK regulatory region in differentiated C2 C12 cell shows that MEF2 is present at all three control regions. 21689639 chr12 7940709 7941994 NANOG NANOG is a homeodomain-containing transcription factor that is essential for the maintenance of pluri_x0002_potency and self-renewal in embryonic stem cells. human Low throughput A Tcf/Lef element within the enhancer region of the human NANOG gene plays a role in promoter activation 不相关 -- HEK-293 cells E_02_0961 Luciferase Reporter Assay Genome sequence analysis of the enhancer region of the human NANOG gene showed the presence of two conserved Tcf/Lef--binding motifs: CAAAGA at positions --1206 to --1190 (designated as Lef #1) and an inverted GTTTCA sequence at ?1020 to ?1004 (designated as Lef #2) (Fig. 1A). To investigate whether Tcf/Lef elements located in the enhancer region play a role in the regulation of NANOG gene transcription, we isolated a 1286--bp fragment of the enhancer region of the human NANOG gene and subcloned it into a firefly luciferase reporter vector, yielding pNanog--Luc(--1286/--1). Enhancer -- Luciferase Reporter Assay NANOG -- -- -- LEF-1,TCF10,TCF1ALPHA,TCF7L3 ChIP -- -- NANOG LEF1 To investigate whether Tcf/Lef elements located in the enhancer region play a role in the regulation of NANOG gene transcription, we isolated a 1286--bp fragment of the enhancer region of the human NANOG gene and subcloned it into a firefly luciferase reporter vector, yielding pNanog--Luc(--1286/--1). ChIP experiments demonstrated that b-catenin and Lef1 bind to the Enhancer region of the NANOG gene. Our present findings would appear to indicate that the Tcf/Lef element in the Enhancer region of the Human NANOG gene functions in transcriptional activation of the Human NANOG gene. 21681857 chr17 42078932 42079032 NAGS N-acetylglutamate synthase (NAGS) catalyzes the conversion of glutamate and acetyl-CoA to NAG, the essential allosteric activator of carbamyl phosphate synthetase I, the first urea cycle enzyme in mammals. human Low throughput N-carbamylglutamate enhancement of ureagenesis leads to discovery of a novel deleterious mutation in a newly defined enhancer of the NAGS gene and to effective therapy 相关 -- Ureagenesis E_02_0962 Luciferase Reporter Assay The remaining change, a homozygous C–A transversion 3,064--bp upstream of the NAGS translation start codon (c.--3064C > A) (Supp. Fig. S1), was determined to be in the recently identified hepatic nuclear factor 1 (HNF--1)bindingsiteofaconservedNAGSregulatoryregion(Fig.4).Transcription factor binding sites in the NAGS enhancer.Transcription factors HNF--1 and NF--Y bind with in the human NAGS enhancer. Enhancer -- Luciferase Reporter Assay AGAS,ARGA -- -- -- HNF-1A,HNF1,HNF4A,IDDM20,LFB1,MODY3,TCF-1,TCF1 Luciferase Reporter Assay -- -- NAGS HNF1A The functional effect of the mutation on NAGS transcription was examined using a luciferase reporter assay, driven by the NAGS enhancer with either the wild--type, mutated, or consensus HNF--1 binding sites.Cells were cotransfected with vector pGL4.74, containing Renilla luciferase hRluc, as a transfection efficiency control. The functional effect of the mutation on NAGS transcription was examined using aLuciferase assay,driven by the NAGS Enhancer with either the wild-type,mutated,or consensus HNF-1 binding sites. Reporter plasmids included the NAGS wild-type promoter with the wild-type Enhancer,4.10WT,the Enhancer containing the patient’s mutation -3064C>A,4.10Pat,or the Enhancer containing the consensus HNF-1 binding site,4.10Con (Fig. 5A). 21673114 chr14 55518040 55518674 NRL The bZIP transcription factor NRL (neural retina leucine zipper) is critical for rod versus cone photoreceptor cell fate choice during retinal development and acts as a molecular switch to produce rods from postmitotic precursors. human Low throughput Combinatorial regulation of photoreceptor differentiation factor, neural retina leucine zipper gene NRL, revealed by in vivo promoter analysis. 否 -- HEK-293 cells E_02_0963 Transfection,EMSA,PCR To refine the cis-regulatory elements involved in controlling Nrl expression further, we tested the sequences within the three conserved clusters by in vivo transfection. Enhancer -- EMSA D14H14S46E -- -- -- Nr1f2,RZR-beta,RZRBeta,hstp,Rorb,Crx1,D14H14S46E,A930035N01Rik,PNR,RNR,rd7 EMSA -- -- Nrl Rorb,Crx,,Nrl,Nr2e3 In silico analysis using the TRANSFAC database (46) revealed a number of conserved putative transcription factor binding sites within B2(transcriptionally active sequence in clusterB)and clusterA(Fig.3,A and B, respectively). To identify the involvement of specific transcription factors, we performed EMSA using several different oligonucleotides spanning the conserved sequence elements(Fig. 4). Electrophoretic mobility shift assays using mouse retinal nuclear extracts, in combination with specific antibodies,demonstrate the binding of retinoid-related orphan nuclear receptor(RORβ),cone rod homeobox,orthodenticle homolog 2,and cyclic AMP response element-binding protein to predicted consensus elements within clusters A and B.Our studies demonstrate Nrl as a direct transcriptional target of RORβ and suggest that combinatorial action of multiple regulatory factors modulates the expression of Nrl in developing and mature retina. 21566115 chr11 44390342 44392251 STAT3 Thus, the STAT3-dependent expression of NFIL3 is a key component of a negative feedback pathway in myeloid cells that suppresses human Low throughput A distal enhancer in Il12b is the target of transcriptional repression by the STAT3 pathway and requires the basic leucine zipper (B-ZIP) protein NFIL3 否 Autoimmune and Inflammatory Diseases bone marrow cell,T Cell E_02_0964 Luciferase Reporter Assay,qRT-PCR We focused on a conserved enhancer about 10kb upstream of the Il12b start site that is targeted by TLR signaling to increase Il12b transcription in response to LPS (33). We made luciferase reporter constructs that fused the Il12b promoter to the upstream enhancer. Enhancer -- Luciferase Reporter Assay,qRT-PCR Il-12b,Il-12p40,Il12p40,p40 -- -- -- AV225605,E4BP4 qRT-PCR,Luciferase Reporter Assay -- -- Il12b Nfil3 To search for transcription factors that could be involved in the suppression of Il12b transcription, we used qRT-PCR to measure the expression of transcription factor mRNAs induced by IL-10 in the presence of an inflammatory costimulus.We made luciferase reporter constructs that fused the Il12b promoter to the upstream enhancer. A NFIL3 binding site is identified in the enhancer region of Il12b. 21556051 chr20 44430820 44433428 UBE3C The UBE3C oncogene is overexpressed in many types of solid tumours including the lethal castration-resistant prostate cancer (CRPC). human Low throughput 不相关 Prostate Cancer LNCaP,PC-3 E_02_0965 RT-PCR,Luciferase Reporter Assay,ChIP,3C we performed quantitative 3C assays for the UBE2C locus in LNCaP and PC-3 cells, in order to identify potential PC-3-specific UBE2C enhancers. Enhancer 3C RT-PCR,Western blot UBCH10,dJ447F3.2 -- -- -- HNF3A,TCF3A,DCML,IMD21,MONOMAC,NFE1B,ETS-1,EWSR2,c-ets-1,p54,OCT1,OTF1,oct-1B ChIP -- -- UBE2C FOXA1,GATA2,POU2F1,ETS1 3C assays were performed at the UBE2C locus to measure crosslinking frequencies between PC-3-specific UBE2C enhancers and the UBE2C promoter To examine whether these transcription factors were differentially recruited to E1,E2 and E3 on chromatin, chromatin immunoprecipitation (ChIP) assays were performed using specific antibodies against FoxA1, GATA2, Oct1 and ETS1 in LNCaP and PC-3 cells treated with or without DHT. 21551367 chr17 32565596 32566796 CCL2 CCL2 plays a seminal role in the re_x0002_cruitment and activation of cells of the monocyte lineage to sites of inflammation (2–4) and for this reason is thought to play a key role in disease states in which monocytes/macrophages influence disease pathogenesis such as atherosclerosis, HIV-1–associated dementia, and tuberculosis. human Low throughput An evolutionarily conserved TNF-alpha-responsive enhancer in the far upstream region of human CCL2 locus influences its gene expression 不相关 -- U-87MG E_02_0966 Luciferase Reporter Assay,PCR,ChIP,EMSA,3C Schematic of CCL2 locus showing regions that were tested in the reporter assays. Enhancer 3C PCR,qPCR GDCF-2,HC11,HSMCR30,MCAF,MCP-1,MCP1,SCYA2,SMC-CF -- -- -- CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NFKB-p105,NFKB-p50,NFkappaB,p105,p50,SP1,C/EBP-beta,IL6DBP,NF-IL6,TCF5 ChIP,EMSA -- -- CCL2 NFKB1,SP1,CEBPB The –16.5 ECR physically interacts with CCL2 proximal promoter.To detect such physical interactions we used the 3C assay. In the 3C assay, interaction between widely separated regulatory elements is detected. The EMSA and the pulldown experiments demonstrated in vitro interaction of the –16.5 ECR with NF-kB and c/EBPb. We used ChIP assay to determine whether the –16.5 ECR can bind NF-kB and c/EBPb in vivo. Sheared chromatin that was obtained from U87MG cells (treated or not treated with TNF-a) was immmu_x0002_noprecipitated with Abs directed against p65 and p50 subunits of NF-kB and c/EBPb or with control Abs. 21549805 chr18 61099404 61099740 SOX11 Accompanying immunohistochemical analysis demonstrates that SOX4 or SOX11 are highly expressed in the majority of hypothalamic GnRH neurons in adult mice. human lymphoid Low throughput Class-C SOX transcription factors control GnRH gene expression via the intronic transcriptional enhancer 否 -- B cell E_02_0967 Luciferase Reporter Assay,EMSA,ChIP luciferase expression was driven by FIRE sequences, and tested these constructs for their responsiveness to PAX5 expression in the RAW264 macrophage cell line and the 38B9 B-cell line using transient transfection assays.When testing the binding of PAX5 across Csf1r by ChIPassays in primary pro-B cells, we noticed that PAX5 did not just bind to the promoter, but also associated with the intronic enhancer (FIRE).This observation was confirmed by EMSA experiments, demonstrating that none of the DNA sequences present on FIRE were capable of competing for the binding of PAX5 to DNA containing a PAX5 consensus sequence. Enhancer -- Immunoprecipitation,Transfection,ChIP AI323359,CD115,CSF-1R,Csfmr,Fim-2,Fim2,Fms,M-CSF-R,M-CSFR -- -- -- BSAP,EBB-1,KLP,Pax-5 ChIP,EMSA -- -- Csf1r Pax5 We performed PAX5-specific chromatin immunoprecipitation analyses across the Csfr1 locus. We investigated the role of PAX5 in regulating Csf1r sense and antisense promoter activity by transient transfections and by employing a Pax5/ proLBcell line expressing an inducible PAX5 protein. When testing the binding of PAX5 across Csf1r by ChIPassays in primary pro-B cells, we noticed that PAX5 did not just bind to the promoter, but also associated with the intronic enhancer (FIRE). PAX5 binds to the intronic enhancer of Csf1r (FIRE).When testing the binding of PAX5 across Csf1r by ChIP assays in primary pro-B cells, we noticed that PAX5 did not just bind to the promoter, but also associated with the intronic Enhancer (FIRE).This observation was confirmed by EMSA experiments. 21536859 chr21 39823183 39825183 ERG Dynamic patterns of chromatin accessibility, transcription factor (TF) binding, and DNA methylation all contribute to the gene expression signature of a cell. human lymphoid Low+High throughput ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer 不相关 T-Cell Acute Lymphoblastic Leukemia T-acute lymphoblastic leukemia (T-ALL),Molt4,REH,416B E_02_0968 Luciferase Reporter Assay,PCR,ChIP,ChIP-PCR,ChIP-seq The ERG stem cell enhancer is active in human T-cell progenitors and in T-ALL.Graphs at right show these peaks of enrichment confirmed by ChIP-PCR. Enhancer q3C qPCR,ChIP-PCR erg-3,p55 -- -- -- DCML,IMD21,MONOMAC,NFE1B,LMO-2,RBTN2,RBTNL1,RHOM2,TTG2,SCL,bHLHa18 ChIP-PCR -- -- ERG GATA2,LMO2,SCL,LYL1 Taken together, these results show that genomic sequences in the human ERG locus corresponding to the mouse Erg +85 enhancer are in an active configuration in CD34+ stem/progenitors, pro-T, and T-ALL cells. ChIP-PCR analysis of TF binding. The enhancer has active chromatin marks (AcH3) in 416B blood progenitors as well as in T-ALL cells. There is strong LMO2 binding in all cell types, whereas SCL and LYL1 enrichments are more pronounced in T-ALL cells. The Ets factors, FLI1 and ERG, are also enriched in T-ALL cells. Consistent with their expression profiles, Gata2 is enriched at the _x0001_85 enhancer in 416B progenitors, whereas GATA3 is enriched in T-ALL cells. 21527503 chr1 33353796 33354196 PRL These studies are consistent with the conclusion that progesterone interferes with PRL/glucocorticoid induction of β-casein transcription by a physical interaction of PR with the promoter and enhancer that blocks assembly of a transcriptional activation complex and dissociation of corepressors and promotes repressive chromatin modifications. human Epithelial Low throughput Progesterone receptor directly inhibits β-casein gene transcription in mammary epithelial cells through promoting promoter and enhancer repressive chromatin modifications 不相关 -- mammary gland epithelial cell E_02_0969 Luciferase Reporter Assay,PCR,ChIP As detected by chromatin immunoprecipitation assays, treatment of cells with the progestin agonist R5020 induced a rapid recruitment (5 min) of PR to the proximal promoter (?235 bp) and distal enhancer (?6 kb upstream of transcription start site) of β-casein Enhancer -- ChIP BCLP,CAC-1,CAC1 -- -- -- STAT5,C/EBP-beta,IL6DBP,NF-IL6,TCF5,DELTA,GADEVS,INO80S,NF-E1,UCRBP,YIN-YANG-1 PCR,ChIP -- -- TMEM54,β-casein gene STAT5B,CEBPB,YY1 In this study, we used HC-11 cells and ChIP assays to examine the influence of progesterone and PR on cooperative interactions and dynamics of the various transcription factors and coregulatory proteins that interact with the promoter and enhancer of the endogenous β-casein gene. Primers for PCR amplification of the proximal promoter span a 170-bp region (-190 to -20 from the transcription start site) containing binding sites for Stat5a,C/EBP,YY1,and GRE/progestin response element (PRE) half-sites, whereas a 400-bp region (-6400 to -6000) of the distal Enhancer was amplified that contains binding sites for Stat5,C/EBP,and other factors. 21486496 chr5 115358083 115360083 MAP2 When neuronal differentiation was induced in embryoid body (EB)-derived neurosphere cells, reporter signals were detected in Msi1-positive NSCs and GFAP-positive astrocytes, but not in MAP2-positive neurons. human Low+High throughput Identification of a novel intronic enhancer responsible for the transcriptional regulation of musashi1 in neural stem/progenitor cells 否 -- embryonic stem cell E_02_0970 Luciferase Reporter Assay,ChIP-seq The deleted BAC constructs were introduced into ESCs, and stable transformants were established for each BAC reporter construct. In a similar manner to the RA treatment and Luciferase reporter assay conducted with EBs (shown in Figure ?Figure2A),the Msi1 transcriptional activities were quantified using the deletion-containing reporters D1-D5 and the full-length BAC reporter D0. These results suggested that the 10-kb region from 55 kb to 65 kb upstream of the TSS might contain Msi1 transcriptional enhancers, and we named this region the 'upstream 10-kb enhancer.' Enhancer -- Luciferase Reporter Assay Msi1h,Musahi1,m-Msi-1 The intronic Enhancer can transactivate Msi1 gene expression with cell-type specificity markedly similar to the endogenous Msi1 expression patterns. Luciferase Reporter Assay Furthermore, when the region after the transcription site (exons and introns coding region) was deleted, the Msi1 transcriptional activity diminished even in the presence of the‘upstream 10-kb Enhancer’ (Figure 3C). These results indicated two regions responsible for Msi2 transcription. 1300003H02Rik,QSOX,Qscn6,SOx,b2b2673Clo,AP-2,AP2alpha,Ap-2(a),Ap2,Ap2tf,Tcfap2a Luciferase Reporter Assay -- -- Msi1 Qsox1,Tfap2a We then used homologous recombination techniques to insert the ffLuc reporter gene into the Msi1 translational initiation site of the RP24-132L16 BAC (Figure1A).The ffLuc reporter gene encodes a fusion protein of the fluorescent protein Venus and firefly Luciferase.This reporter gene both visualized Msi1 transcriptional activity in vivo, and allowed us to use Luciferase bioluminescence to quantify the level of transcriptional activity. Through these investigations, we have identified a new Msi1 transcription Enhancer element in NS/PCs. This region is located in the 595-bp region within the sixth intron of the Msi1 gene, and contains SOX- and AP-2-binding sites. 21454523 chr7 103823354 103846754 CTCF However, the underlying mechanisms are unclear. The CCCTC-binding factor, CTCF, binds to the insulator elements at the 5′ and 3′ boundaries of the locus, but these sites were shown to be dispensable for globin gene activation. human Low throughput Cohesin mediates chromatin interactions that regulate mammalian β-globin expression 否 Haploinsufficiency 745A E_02_0971 ChIP,qRT-PCR,3C The presence of the cohesin holo-complex was confirmed by ChIP using antibodies specific for SMC1 and SA1.Most notably, HS2 functions as an enhancer, and the outer HS5 functions as an insulator. B, adult β-globin gene induction following DMSO treatment. End point RT-PCR of β-major gene induction and q-RT-PCR analysis of β-major and β-minor genes in comparison to GAPDH were examined over 4 days of DMSO treatment. Q-RT-PCR values were normalized to ribonuclease/angiogenin inhibitor 1 (rnh1). Enhancer 3C ChIP Ey,Hby Nipped-B-like (Nipbl) bind to the locus control region (LCR) at the CTCF insulator and distal enhancer regions as well as at the specific target globin gene that undergoes activation upon differentiation ChIP,3C,PCR The results indicate that cohesin binds to these regions when they interact. Taken together, cohesin and Nipbl are recruited not only to the HS5 insulator, but also to the Enhancer and the active _x005f_x0001_-globin gene regions. This correlates with the induction of the interaction of these domains and β-globin gene activation. Idn3,AW108038,NF-E2,NF-E2/P45,p45,p45NFE2,p45nf-e2 ChIP -- -- Hbb-y Nipbl,Ctcf,Nfe2 3C and ChIP-loop analysis of the HS2 and β-major promoter interaction at 4 days after DMSO treatment. The interactions of a region containing HS4 and HS5 (HS4/5) with either 3′HS1 or HS-62 are compared. Differentiation-induced Cohesin and Nipbl Binding at the β-globin Locus Is Associated with LCR Enhancer-globin Gene Interactions.,ChIP analysis of cohesin (Rad21),Nipbl,CTCF, and NF-E2 binding to the β-globin locus. 21445863 chr21 35982223 35983306 RUNX1 The transcription factor RUNX1 is a key regulator of haematopoiesis in vertebrates. human Low throughput Transcriptional regulation and spatial organisation of the human AML1/RUNX1 gene 不相关 -- Acute T-Cell Leukaemia Cell E_02_0972 Luciferase Reporter Assay,PCR To test the putative enhancer activity of RE1 and RE2, we made a number of genetic constructs with a pGL3--Basic vector, which contains the firefly Luciferase gene. Enhancer -- Luciferase Reporter Assay AML1,AML1-EVI-1,AMLCR1,CBF2alpha,CBFA2,EVI-1,PEBP2aB,PEBP2alpha -- -- -- -- -- -- -- RUNX1,RUNX1 --,-- The promoters were cloned upstream from the Luciferase gene and candidate enhancer elements-downstream of the gene in direct genomic orientation and reverse genomic orientation relative to the corresponding promoter.;The promoters were cloned upstream from the Luciferase gene and candidate enhancer elements-downstream of the gene in direct genomic orientation and reverse genomic orientation relative to the corresponding promoter. --;-- 21419113 chr1 226065482 226067482 LEFTY1 We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryo. human Low throughput Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos 不相关 -- Perinodal cell E_02_0973 PCR,Transgenic mice,Immunostaining We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryos.the enhancer activity of each fragment was examined in transgenic mouse embryos. Enhancer -- PCR,Transgenic mice,Immunostaining LEFTB,LEFTYB -- -- -- FAST-1,FAST1 X-Gal Staining Assay -- -- LEFTY1 FOXH1 We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryos. The approximate location of FoxH1 binding sites is indicated by red ovals. Restriction sites: E, EcoRI; Bam, BamHI; BgI, BglI; BX, BstXI; BgII, BglII; Sma, SmaI; Xb, XbaI; Sac, SacI. (B–E) Ventral views of X-gal–stained embryos harboring the indicated lacZ transgenes. (F–I) Magnified views of the node region of X-gal–stained embryos harboring hNPE7.5-lacZ. 21378152 chr11 32403489 32405489 WT1 The WT1 reduction may be a useful marker for early podocyte injury. human Low throughput TGF-beta1 reduces Wilms' tumor suppressor gene expression in podocytes 不相关 -- Human Podocyte Cell Line AB8/13 E_02_0974 qRT-PCR,Luciferase Reporter Assay We tested the effect of TGF-beta1 on a human WT1 enhancer located ?4.3 kb upstream of the transcription start site using a reporter vector WTA. Enhancer -- qRT-PCR,Luciferase Reporter Assay AWT1,GUD,NPHS4,WAGR,WIT-2,WT33 -- -- -- DPC4,JIP,MADH4,MYHRS Luciferase Reporter Assay -- -- WT1 SMAD4 TGF-beta1 did not alter luciferase activity of the reporter construct for a human WT1 promoter but reduced that for a human WT1 5′ enhancer construct, suggesting that TGF-beta1 may regulate WT1 expression by altering the 5′ enhancer activity. The luciferase activity of p3TP-lux, a reporter construct for Smadbinding element, was determined after incubation with 5 ng/mL TGFbeta1 for 24 h. TGF-beta1 increased the luciferase activity by ~12-fold in the presence of the NTC shRNA, while this increase was largely prevented by Sh-Smad4. The luciferase activity of p3TP-lux was normalized to beta-galactosidase activity of pCMV-beta-gal and shown as relative values to that of pGL2 basic. 21355081 chr10 131265598 131265656 MGMT These studies provide strong evidence that the A allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in lung carcinogenesis. Moreover, TMZ treatment may benefit a subset of lung cancer patients methylated for MGMT. human Epithelial tissues, carcinoma Low throughput The A/G allele of rs16906252 predicts for MGMT methylation and is selectively silenced in premalignant lesions from smokers and in lung adenocarcinomas 相关 rs16906252 Lung Adenocarcinoma bronchial epithelial cell E_02_0975 Luciferase Reporter Assay,PCR This study provides strong evidence that the A allele of a MGMT promoter-enhancer SNP (rs16906252) is a key determinant in the acquisition of MGMT methylation in lung carcinogenesis. Enhancer -- Luciferase Reporter Assay,PCR MGMT -- -- -- -- -- 131265545 Luciferase Reporter Assay,PCR MGMT -- This study provides strong evidence that the A allele of a MGMT promoter-enhancer SNP (rs16906252) is a key determinant in the acquisition of MGMT methylation in lung carcinogenesis. -- 21331042 chr3 34563695 34565695 Tbx6 An enhancer N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation in the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. mouse Low throughput Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells 否 -- stem cell E_02_0976 EMSA,Immunostaining,Transgenic mice Our earlier studies have indicated that among a number of enhancers regulating Sox2, enhancer N1 is responsible for Sox2 activation in the caudally extendin neural plate5,6 (Fig.1a-c; Supplementary Fig.1). Enhancer -- EMSA,Immunostaining Sox-2,lcc,ysb -- -- -- rv EMSA -- -- Sox2 Tbx6 Finally, we asked whether the suppression of Sox2 enhancer N1 activation by Tbx6 involves direct interaction of the Tbx6 protein with the enhancer N1 DNA sequence. Various overlapping fragments of the N1 sequence were tested for Tbx6 binding using electrophoretic mobility shift assays (EMSA). Exogenous Sox2-HA was successfully expressed in the caudal-most mesodermal compartment (Fig.4b), as indicated by HA-tag immunostaining and the mesodermal Sox2 immunostaining (Fig.4c-e). This result demonstrates that Sox2 expression is sufficient for the initiation of neural tube development from the primitive paraxial mesoderm, even in wild type embryos. Various overlapping fragments of the N1 sequence were tested for Tbx6 binding using electrophoretic mobility shift assays (EMSA). 21310710 chr18 60786011 60788011 BCL2 The 279-bp major breakpoint region (mbr) within the 3'-untranslated region (3'-UTR) of the BCL2 gene is a binding site of special AT-rich sequence binding protein 1 (SATB1) that is well known to participate in the long-range regulation of gene transcription. human Low throughput The BCL2 gene is regulated by a special AT-rich sequence binding protein 1-mediated long range chromosomal interaction between the promoter and the distal element located within the 3'-UTR 不相关 -- jurkat cell E_02_0977 3C,ChIP,RT-PCR With chromosome conformation capture (3C) and chromatin immunoprecipitation (ChIP) assays we demonstrated that the mbr could physically interact with BCL2 promoter through SATB1-mediated chromatin looping, which was required for epigenetic modifications of the promoter, CREB accessibility and high expression of the BCL2 gene. Enhancer 3C ChIP,RT-PCR Bcl-2,PPP1R50 -- -- -- SATB1,C/EBP-beta,IL6DBP,NF-IL6,TCF5,KAT3B,MKHK2,RSTS2,p300 Western blot,3C,RT-PCR -- -- BCL2 SATB1,CEBPB,EP300 With chromosome conformation capture (3C) and chromatin immunoprecipitation (ChIP) assays we demonstrated that the mbr could physically interact with BCL2 promoter through SATB1-mediated chromatin looping, which was required for epigenetic modifications of the promoter, CREB accessibility and high expression of the BCL2 gene. Our data showed that a reduction of the interaction between SBS1 and mbr induced by knockdown of SATB1 was significantly correlated with a decrease in the BCL2 mRNA level , suggesting that SATB1-mediated mbr-promoter interaction was required for transcriptional activity of the gene. 21087445 chr22 24236392 24237411 MIF Mithramycin inhibited expression of MIF in CEMC7A cells. This effect was specific to the intronic enhancer and was not seen on the MIF promoter. human kidney,lung Low throughput Identification of a novel cell type-specific intronic enhancer of macrophage migration inhibitory factor (MIF) and its regulation by mithramycincei_4289 178..1 Rheumatoid Arthritis RA-FLS，A549，HEK293TTHP-1293T，SW982 cell E_02_0978 Luciferase Reporter Assay,PCR,EMSA,DNaseI-seq DNase I hypersensitivity was used to identify potential hypersensitive sites (HS) across the MIF gene locus. Reporter gene assays were performed in different human cell lines with constructs containing the native or mutated HS element. Following phylogenetic and transcription factor binding profiling, electrophoretic mobility shift assay (EMSA) and RNA interference were performed and the effects of incubation with mithramycin, an antibiotic that binds GC boxes, were also studied. An HS centred on the first intron of MIF was identified. The HS acted as an enhancer in human T lymphoblasts (CEMC7A), human embryonic kidney cells (HEK293T) and human monocytic cells (THP-1), but not in a fibroblast-like synoviocyte (FLS) cell line (SW982) or cultured FLS derived from rheumatoid arthritis (RA) patients. Enhancer -- Luciferase Reporter Assay,PCR,EMSA,DNaseI-seq GIF,GLIF,MMIF -- -- -- SP1 Luciferase Reporter Assay,EMSA -- -- MIF SP1 DNase I hypersensitivity was used to identify potential hypersensitive sites (HS) across the MIF gene locus. Reporter gene assays were performed in different human cell lines with constructs containing the native or mutated HS element. Following phylogenetic and transcription factor binding profiling, electrophoretic mobility shift assay (EMSA) and RNA interference were performed and the effects of incubation with mithramycin, an antibiotic that binds GC boxes, were also studied. An HS centred on the first intron of MIF was identified. The HS acted as an enhancer in human T lymphoblasts (CEMC7A), human embryonic kidney cells (HEK293T) and human monocytic cells (THP-1), but not in a fibroblast-like synoviocyte (FLS) cell line (SW982) or cultured FLS derived from rheumatoid arthritis (RA) patients. In order to determine whether Sp1 is recruited to the MIF intron 1 Enhancer, EMSA was performed using CEMC7A nuclear extract and a radiolabelled DNA probe of the 5′region of the intronic sequence.We were able to demonstrate that Sp1 bound this sequence, as competition with excess cold Sp1 consensus sequence and addition of Sp1-specific antibody resulted in the abrogation of a shifted complex. 21056086 chr1 23881789 23881796 BMP2 Bone morphogenetic protein 2 (BMP2) stimulates expression of the inhibitors of DNA binding (Id) 1, 2, and 3 in a variety of cell types. human Low throughput Mechanisms of bone morphogenetic protein 2 (BMP2) stimulated inhibitor of DNA binding 3 (Id3) transcription 否 -- E_02_0979 qRT-PCR,Luciferase Reporter Assay,ChIP To determine if these base pairs also play a role in BMP2induction of the human ID3 promoter, we introduced mutations comparable to Mut4 and Mut5 in the murine Id3 promoter into the minimal hID3 promoter--reporter construct (?653/+402 ID3--luc) (Fig. 6(B)). Enhancer -- ChIP HEIR-1,bHLHb25 A more distal Enhancer was shown to mediate BMP4-induction of the human ID3 gene in ovarian cancer cells. ChIP We identified the same sequence in the murine gene (?3283/?3276) and observed through ChIP analysis that BMP2 stimulated recruitment of SMAD1 to this region of the endogenous Id3 gene in LT2 cells. Mutation of the distal BRE in the longer murine Id3 reporter greatly reduced, but did not abolish, BMP2 induction. BDA2A, SSFSC, BMP2 ChIP -- -- ID3,ID3 BMP2,BMP2 We identified the same sequence in the murine gene (?3283/?3276) (Fig. S8) and observed through ChIP analysis that BMP2 stimulated recruitment of SMAD1 to this region of the endogenous Id3 gene in L?T2 cells;We identified the same sequence in the murine gene (?3283/?3276) (Fig. S8) and observed through ChIP analysis that BMP2 stimulated recruitment of SMAD1 to this region of the endogenous Id3 gene in L?T2 cells We identified the same sequence in the murine gene (?3283/?3276) (Fig. S8) and observed through ChIP analysis that BMP2 stimulated recruitment of SMAD1 to this region of the endogenous Id3 gene in LβT2 cells (Fig. S7A). Muta_x0002_tion of the distal BRE in the longer murine Id3 reporter greatly reduced, but did not abolish, BMP2 induction.;We identified the same sequence in the murine gene (?3283/?3276) (Fig. S8) and observed through ChIP analysis that BMP2 stimulated recruitment of SMAD1 to this region of the endogenous Id3 gene in LβT2 cells (Fig. S7A). Muta_x0002_tion of the distal BRE in the longer murine Id3 reporter greatly reduced, but did not abolish, BMP2 induction. 20942803 chr15 52315678 52316298 SLC30A8 The SLC30A8 gene encodes the zinc transporter ZnT-8, which provides zinc for insulin-hexamer formation. human lymphoid Low throughput The pancreatic islet β-cell-enriched transcription factor Pdx-1 regulates Slc30a8 gene transcription through an intronic enhancer 否 -- insulin secreting cell E_02_0980 Luciferase Reporter Assay,PCR To address this hypothesis these regions, designated intronic enhancers A and B, respectively, were isolated using PCR and ligated 5′ of a heterologous thymidine kinase (TK)-luciferase fusion gene containing TK genomic sequence between ?105 and +51, relative to the transcription start site.Luciferase expression directed by these fusion genes was then analyzed by transient transfection of βTC-3 cells, an islet beta cell-derived line [31], αTC-6 cells, an islet alpha cell-derived line [32, 33] and HeLa cells, a cervix-derived cell line. Enhancer -- PCR,Luciferase Reporter Assay C820002P14Rik,ZnT-8,ZnT8 -- -- -- 2310056B04Rik,D230003C07Rik,Pbx-1 ChIP,EMSA -- -- Slc30a8 Pbx1 Luciferase expression directed by these fusion genes was then analyzed by transient transfection of βTC-3 cells, an islet beta cell-derived line [31], αTC-6 cells, an islet alpha cell-derived line [32, 33] and HeLa cells, a cervix-derived cell line. Figure 2 shows that in βTC-3 cells, but not αTC-6 or HeLa cells, intronic enhancer A elevated reporter gene expression beyond that driven by the TK-luciferase fusion gene alone, indicating that this region is an islet beta cell-specific enhancer. In contrast, intronic enhancer B had no effect on fusion gene expression in any of the cell lines. Gel retardation and chromatin immunoprecipitation (ChIP) assays revealed that the islet-enriched transcription factor Pdx-1 binds Enhancer A in vitro and in situ, respectively. 20878775 chr13 53463266 53463541 Dlx5 Here, we provide a molecular description of the cooperative effects of BMP and Wnt canonical pathway on the expression of the early osteogenic genes Dlx5, Msx2, and Runx2 in C2C12 cells, primary cultures of bone marrow-mesenchymal stem cells, and organotypic calvarial cultures. mouse Low throughput Conserved regulatory motifs in osteogenic gene promoters integrate cooperative effects of canonical Wnt and BMP pathways 否 -- E_02_0981 PCR,Luciferase Reporter Assay The murine Dlx5 promoter from -1036 to +30 was obtained by polymerase chain reaction (PCR) and cloned in the pGL2basic vector. Murine Msx2 and Runx2 enhancers (from -3340 to -3615 for Msx2 and from -1170 to -1388 for Runx2) also were obtained by PCR and subcloned in the minimal promoter of c-fos promoter. Enhancer -- Luciferase Reporter Assay BB122635,Hox-8,Hox8,Hox8.1 -- -- -- BB122635,Hox-8,Hox8,Hox8.1,AV237891,Dlx-3,AI385752,Atf-4,C/ATF,CREB2,TAXREB67,AML3,Cbf,Cbfa-1,Cbfa1,LS3,Osf2,PEBP2aA,Pebp2a1,Pebpa2a,6430578P22Rik,C22,Osx qRT-PCR,Luciferase Reporter Assay,ChIP -- -- Msx2,Msx2 Msx2,Dlx3,Dlx5,Atf4,Runx2,Sp7,Msx2,Dlx3,Dlx5,Atf4,Runx2,Sp7 The Msx2 gene shows a conserved region 3.5 kb upstream of the transcriptional start site, which also includes a combination of a TCF/LEF1 box and both GC-rich and CAGA SBEs. This region has been shown to be necessary and sufficient to confer BMP responsiveness in vitro and in vivo.Finally, a similar enhancer is located 1 kb upstream of the P1 osteoblast-specific promoter of the Runx2 gene (Supplemental Fig. S3). To test whether these regions have the ability to render responsiveness to Wnt3a and/or BMP-2, we generated the corresponding luciferase constructs and assayed them in C2C12 cells. ;The Msx2 gene shows a conserved region 3.5 kb upstream of the transcriptional start site, which also includes a combination of a TCF/LEF1 box and both GC-rich and CAGA SBEs. This region has been shown to be necessary and sufficient to confer BMP responsiveness in vitro and in vivo.Finally, a similar enhancer is located 1 kb upstream of the P1 osteoblast-specific promoter of the Runx2 gene (Supplemental Fig. S3). To test whether these regions have the ability to render responsiveness to Wnt3a and/or BMP-2, we generated the corresponding luciferase constructs and assayed them in C2C12 cells. To confirm that cooperative transcriptional interactions between canonical Wnt signaling and the Smad pathway on osteogenic genes occur in vivo, ChIP assays were performed in C2C12 cells.As shown in Fig.7D,TCF4,b-catenin,and Smad1 and Smad4 interacted with the responsive regions of Dlx5, Msx2, and Runx2 genes in vivo.;To confirm that cooperative transcriptional interactions between canonical Wnt signaling and the Smad pathway on osteogenic genes occur in vivo, ChIP assays were performed in C2C12 cells.As shown in Fig.7D,TCF4,b-catenin,and Smad1 and Smad4 interacted with the responsive regions of Dlx5, Msx2, and Runx2 genes in vivo. 20093418 chr6 35574362 35576362 TULP1 However, the expression of C6orf81 or that of TULP1 showed no significant response to dex treatment in A549 cells human skin Low throughput Glucocorticoid receptor activates poised FKBP51 locus through long-distance interactions -- A549 cell E_02_0982 RT-qPCR,ChIP According to our quantitative ChIP and enhancer assays, there are at least three major distal gene regions that significantly bind GR and also function as strong GR-regulated enhancers in isolation. Enhancer -- ChIP,Luciferase Reporter Assay FKBP51,FKBP52,FKBP59,HBI,Hsp56,PPIase,p52 -- -- -- MRD21 ChIP -- -- FKBP4 CTCF Our quantitative chromatin immunoprecipitation scans and enhancer activity analyses indicate that activation of the FKBP51 locus by glucocorticoids in vivo is triggered by the loading of GR to enhancers at about 34 kb 5 and about 87 kb 3 of the transcription start site. We used the genome-wide CTCF-binding information from the CTCF-binding site database for choosing the regions to be ChIP scanned with anti-CTCF antibody. 19773398 chrx 30317939 30318739 NR0B1 . A reporter construct lacking this enhancer element upstream of NR0B1 was unresponsive to SF-1 transcrip_x0002_tional activation human blood Low throughput X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism caused by an inversion disrupting a conserved noncoding element upstream of the NR0B1 (DAX1) gene X-Linked Congenital Adrenal Hypoplasia HEK-293 cells E_02_0983 Luciferase Reporter Assay,PCR Luciferase reporter gene activity in transiently transfected HEK293 cells. Relative luciferase activity refers to the activity of the firefly reporter gene normalized to Renilla luciferase internal control for transfection efficiency. Firefly reporter constructs contained the DAX1 conserved noncoding “enhancer” elements upstream of a minimal thymidine kinase promoter driving the firefly reporter. Enhancer -- Luciferase Reporter Assay,PCR AHC,AHCH,AHX,DAX-1,DAX1,DSS,GTD,HHG,NROB1,SRXY2 A reporter construct lacking this Enhancer element upstream of NR0B1 was unresponsive to SF-1 transcriptional activation. Luciferase Reporter Assay SF-1 acted as an activator on the wild-type construct, whereas the mutant construct,lacking the SF-1 consensus binding site, showed no response to SF-1. AD4BP,ELP,FTZ1,FTZF1,POF7,SF-1,SF1,SPGF8,SRXX4,SRXY3,hSF-1 Luciferase Reporter Assay -- -- NR0B1 NR5A1 Our results therefore strongly suggest the existence of an SF-1 binding site 4kb upstream of NR0B1 that acts as an enhancer of DAX1 expression. Luciferase reporter gene activity in transiently transfected HEK293 cells. Relative luciferase activity refers to the activity of the firefly reporter gene normalized to Renilla luciferase internal control for transfection efficiency. The mutant CNE is unresponsive to the transcription enhancement seen in the presence of cotransfected SF-1. 19708858 chr3 48598405 48598558 Ucn2 Site-directed mutagenesis experiments demonstrated that HRE1 is required for HIF1α- dependent luciferase activation mouse rhabdomyosarcoma Low throughput The human urocortin 2 gene is regulated by hypoxia: identification of a hypoxia-responsive element in the 3?-flanking region Myocardial Ischemia TE-671 E_02_0984 Luciferase Reporter Assay,RT-PCR This activation was conserved in constructs with the 3' FLR fragment placed upstream of the luciferase gene, indicating an enhancer function for HRE1.To test their role as enhancers, we cloned several fragments of the 3 'FLR of the hUcn2 gene downstream of the firefly luciferase gene in (a) the pGL3 ?746 bp vector containing the functional hUcn2 promoter, and (b) the pGL3control vector containing an internal SV40 promoter (Figure 2A). Enhancer -- Luciferase Reporter Assay,Transfection SRP,UCN-II,UCNI,UR,URP Hypoxia induces hUcn2 expression via a specific HRE in the 3 FLR of the hUcn2 gene, which interacts with the transcription factor HIF1α. Luciferase Reporter Assay Similar to the results obtained with constructs that contained the 3' FLR3 variants downstream of the luciferase gene, the hypoxia- and CPX-induced luciferase activation was strongest in the 3' FLR3 containing both wild-type HRE1 and HRE2. HIF-1-alpha,HIF-1A,HIF-1alpha,HIF1,HIF1-ALPHA,MOP1,PASD8,bHLHe78 ELISA -- -- UCN2 HIF1A To test their role as enhancers, we cloned several fragments of the 3 ' FLR of the hUcn2 gene downstream of the firefly luciferase gene in (a) the pGL3 ?746 bp vector containing the functional hUcn2 promoter, and (b) the pGL3control vector containing an internal SV40 promoter (Figure 2A). TE--671 cells were transfected with the different constructs and exposed to normoxia or hypoxia for 12 h. Hypoxia significantly increased luciferase expression, specifically in the constructs containing the fragment 3 'FLR3 (Figure 2A). To prove that HIF1α binds to HRE1 and HRE2 in the 3_x0002_FLR of the hUcn2 gene, we performed HIF1α binding and competition ELISA assays. After 12 h of hypoxia, binding of HIF1α to the EPO HRE was stronger than under normoxic conditions. 19285986 chr16 67519201 67519833 ATP6V0D1 we show here that two adjacent enhancers inside the first intron of the neighboring (1.4 kb downstream) ATPase gene (ATP6V0D1) modulate the human AgRP promoter with profound spatiotemporal variation despite their diminutive sizes (221 and 231 nt) human kidney Low throughput Control Elements in the Neighboring ATPase Gene Influence Spatiotemporal Expression of the Human Agouti-Related Protein -- H295R,N38 E_02_0985 Transgenic mice,Luciferase Reporter Assay Schematic representation of the genomic region encompassing the AgRP and the ATPase locus. Expression constructs for regions A, B, C, and D were directionally cloned into pGL3-basic luciferase vector.Regions C and D were evaluated in the same fashion. Region D (but not region C) contained enhancer elements in both neuronal and somatic cell types (Fig. 1a). Region D was therefore divided into three overlapping sub-regions: Di(-18/+312)(+2727/+3359), Dii(-18/+312) (+3341/+3941), and Diii(-18/+312)(+3943/+4575). Sub-regions Di and Diii (but not Dii) had enhancer properties for the AgRP basal promoter in both h295R and N38 cell lines (Fig. 1b).Fig. 1. In vitro determination of enhancer elements Enhancer -- Transgenic mice,Luciferase Reporter Assay AGRT,ART,ASIP2 -- -- -- -- -- -- -- AGRP -- Region D (but not C) increased activity of the human AgRP promoter, equally in the human adrenocortical NCI-h295R and the mouse clonal hypothalamic N38 cell lines. -- 19141476 chr5 147205131 147212149 Pdx1 In addition, occupancy of the well-characterized proximal Pdx1 enhancer by Foxa1 and Foxa2 is developmental stage-dependent. mouse nonpancreatic Low+High throughput Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development 否 Pancreatic Hypoplasia pancreatic A cell E_02_0986 ChIP,ChIP-seq Using chromatin immunoprecipitations (ChIP) and ChIP sequencing (ChIP-Seq) of fetal pancreas and islet chromatin, we demonstrate that Foxa1 and Foxa2 predominantly occupy a distal Enhancer at -6.4 kb relative to the transcriptional start site in the Pdx1 gene. Enhancer -- ChIP IDX-1,IPF-1,Ipf1,Mody4,STF-1,pdx-1 -- -- -- HNF3-beta,HNF3beta,Hnf-3b,Hnf3b,Tcf-3b,Tcf3b,Hnf-3a,Hnf3a,Tcf-3a,Tcf3a ChIP -- -- Pdx1 Foxa2,Foxa1 We performed chromatin immunoprecipitation (ChIP) as_x0002_says with antibodies specific to either Foxa1 or Foxa2 on chromatin isolated from primary mouse islets. Both Foxa1 and Foxa2 bound to the Area I–II–III enhancer of Pdx1 in vivo. We performed chromatin immunoprecipitation (ChIP) assays with antibodies specific to either Foxa1 or Foxa2 on chromatin isolated from primary mouse islets. Both Foxa1 and Foxa2 bound to the Area I–II–III Enhancer of Pdx1 in vivo .Notably, the binding of Foxa2 to Area IV or Area I–II–III is signifi-cantly enhanced in pancreatic islets compared with fetal pancreas. 19041414 chr15 97977739 97977942 Sox9 We have previously reported that TGF-β-regulated Smad3 induces chondrogenesis through the activation of Sox9-dependent transcription. mouse Cancer Low throughput Smad3 activates the Sox9-dependent transcription on chromatin 否 -- HeLa cell E_02_0987 Luciferase Reporter Assay,EMSA Transient transfections of Sox9, Smad3, and T_x0002_R-I(TD) did not increase luciferase activities of pGL3-B plasmids in SW1353 cells (pGL3-B). In pGL3-585E systems, Sox9 enhanced a relative luciferase activity to a level as high as 2.2-fold over the control. Cotransfection of Smad3 augmented a luciferase activity up to 2.3-fold higher level of Sox9-transfected cells. The additional transfection of constitutively active form of T_x0002_R-I(TD) induced an approximately 36% increase of the activity in Sox9- and Smad3-transfected SW1353 cells. Luciferase activities of pGL3-585E were not increased in the absence of Sox9. Note that Smad3 and T_x0002_R-I(TD) synergistically activated the native Col2a1 reporter-mediated transcription in a Sox9-dependent manner. Enhancer -- Luciferase Reporter Assay,EMSA Col2,Col2a,Col2a-1,Del1,Dmm,Lpk,M100413,Rgsc413,Rgsc856 -- -- -- 2010306G03Rik,AV220920,mKIAA4243 EMSA -- -- Col2a1 Sox9 Purified Sox9 associated with the Col2a1 enhancer probe in EMSA. Purified Sox9 associated with the Col2a1 enhancer probe in EMSA. The unlabeled competitor decreased the signal of Sox9–DNA complex. Supershifted band was observed in the presence of anti-Sox9 antibody. 18552207 chr7 126406352 126406616 Cd19 We identified a B cell-specific upstream enhancer and showed that the developmental regulation of Cd19 expression involves precisely coordinated alterations in transcription factor binding and chromatin remodeling at Cd19 cis-regulatory elements. mouse lymphoid Low throughput Stem cell-specific epigenetic priming and B cell-specific transcriptional activation at the mouse Cd19 locus 否 -- B Cell,T Cell E_02_0988 Luciferase Reporter Assay,ChIP Transient transfection assays in different mouse cell lines. A mouse Cd19 promoter reporter construct (_x005f_x005f_x005f_x005f_x005f_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x005f_x005F_x0007_7 to _x005F_x0007_200 bp; e) or a construct containing the _x0007_2 kb DHS (_x0007_1832 to _x0007_2096 bp) combined with the Cd19 promoter (f) was transiently transfected into various cell lines. The relative activity was determined as the luciferase activity of each construct over control vector pXPG. Data represent the mean of 2 to 4 experiments performed in triplicate Enhancer -- ChIP AW495831 Enhancer is involved in the regulation of tissue specific expression of Cd19 Transfection As previously reported in human cells, the promoter was active in all analyzed cell types (Figure 1C white bars). In contrast, the -2 kb DHS had Enhancer activity only in B cells (Figure 1C black bars), providing evidence that this Enhancer is involved in the regulation of tissue specific expression of Cd19. A1,AA408400,ALF2,AW209082,E12,E12/E47,E2A,E47,KA1,ME2,Pan1,Pan2,TCF-3,Tcfe2a,VDIR,bHLHb21,Ebf,O/E-1,OE-1,Olf-1,Olf1,BSAP,EBB-1,KLP,Pax-5 ChIP,DMS Footprinting Assay -- -- Cd19 Tcf3,Ebf1,Pax5 As previously reported in human cells, the promoter was active in all analyzed cell types (Figure 1C white bars). In contrast, the _x005F_x0007_2 kb DHS had enhancer activity only in B cells (Figure 1C black bars), providing evidence that this enhancer is involved in the regulation of tissue specific expression of Cd19. We performed an in vivo DMS footprinting assay to answer the question of which transcription factors bind to the Cd19 promoter and enhancer.The specific binding of these proteins was confirmed by ChIP analysis, demonstrating that EBF and PAX5 bound to the enhancer in B cells and that E2A bound in B and T cells. 12861010 chr11 5293686 5294250 CTCF We describe enhancer-blocking or boundary elements on either side of the locus that are bound in vivo by the transcription factor CTCF, but we found that they do not coincide with transitions in nuclease sensitivity flanking the locus or with patterns of histone modifications within it. human adult erythroid Low throughput A Complex Chromatin Landscape Revealed by Patterns of Nuclease Sensitivity and Histone Modification within the Mouse 尾-Globin Locus 否 -- Pleen cell,MEL cell E_02_0989 PCR,DNaseI-seq We have also found DNase I HSs at kb -85.5 (HS-85.5) and -84.5 in mouse, but there is no corresponding se_x0002_quence or structure in human for these HSs.By comparison,neither the active _x0002_maj-globin gene promoter nor a region located ~1 kb from HS5 shows significant enrichment. HS-85.5 exhibits a modest (twofold) enrichment. Enhancer -- DNaseI-seq,Southern blot,PCR LOC110006319 -- -- -- MRD21 ChIP -- -- LOC110006319 CTCF In ery_x0002_throid cells, the active _x0002_-globin locus contains several DNase I HSs, which have been shown to map to sequences with regu_x0002_latory functionIn addition, histone hyperacetylation anddimethylation of histone H3 K4 are not uniform features of the nuclease-sensitive mouse _x0001_-globin domain but rather define distinct subdomains within it. Our results reveal a complex chromatin landscape for the active _x0001_-globin locus and illustrate the complexity of broad structural changes that accompany gene activation. To determine whether CTCF binds to these sequences in vivo, we performed ChIP analysis using antibodies to CTCF.