About Enhancer

Enhancer ID: E_01_0429
Species: human
Position : chr18:63121048-63123048
Biosample name:
Experiment class : High+Lowthroughput
Enhancer type: Enhancer
Disease: Acute promyelocytic leukemia (apl)
Pubmed ID:  29876014
Enhancer experiment: NGS,ChIP,RNA extraction,RT-PCR,Whole-genome bisulfite sequencing(WGBS),RNA-seq
Enhancer experiment description: 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.

About Target gene

Target gene : AK2
Strong evidence: qRT-PCR,qPCR,ChIP,3C
Less strong evidence: RNA-Seq
Target gene experiment description: 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.

About TF

TF name : BCL2
TF experiment: NGS,ChIP,RNA extraction,RT-PCR,Whole-genome bisulfite sequencing(WGBS),RNA-seq
TF experiment description: 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.

About Function

Enhancer function : 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 function experiment: Immunohistochemical staining
Enhancer function
experiment description:
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.

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
BCL2 Activation of BAD and translocation to mitochondria reactome 15
BCL2 Apoptosis signaling pathway panther 104
BCL2 ATF-2 transcription factor network pid 59
BCL2 BCR netpath 161
BCL2 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members reactome 8
BCL2 C-MYB transcription factor network pid 87
BCL2 Caspase Cascade in Apoptosis pid 57
BCL2 Ceramide signaling pathway pid 49
BCL2 Direct p53 effectors pid 141
BCL2 EGFR1 netpath 475
BCL2 EPO signaling pathway pid 33
BCL2 HIV-1 Nef: Negative effector of Fas and TNF-alpha pid 33
BCL2 IL2-mediated signaling events pid 54
BCL2 IL2 netpath 81
BCL2 IL2 signaling events mediated by PI3K pid 38
BCL2 IL2 signaling events mediated by STAT5 pid 30
BCL2 IL3 netpath 84
BCL2 Oxidative stress response panther 23
BCL2 Role of Calcineurin-dependent NFAT signaling in lymphocytes pid 54
BCL2 RXR and RAR heterodimerization with other nuclear receptor pid 26
BCL2 Signaling events mediated by Stem cell factor receptor (c-Kit) pid 53
BCL2 Validated targets of C-MYC transcriptional repression pid 63
BCL2 Protein processing in endoplasmic reticulum kegg 166
BCL2 Apoptosis kegg 88
BCL2 Focal adhesion kegg 197
BCL2 Neurotrophin signaling pathway kegg 126
BCL2 Amyotrophic lateral sclerosis (ALS) kegg 53
BCL2 Toxoplasmosis kegg 131
BCL2 Pathways in cancer kegg 321
BCL2 Colorectal cancer kegg 63
BCL2 Prostate cancer kegg 85
BCL2 Small cell lung cancer kegg 83
BCL2 Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
BCL2 Hs_Apoptosis_Modulation_and_Signaling_WP1772_91293 wikipathways 71
BCL2 Hs_Integrated_Cancer_Pathway_WP1971_82939 wikipathways 33

Enhancer associated network

The number on yellow line represents the distance between enhancer and target gene

Expression of target genes for the enhancer


Enhancer associated SNPs