About Enhancer

Enhancer ID: E_02_0802
Species: human
Position : chr3:107702615-107714185
Biosample name:
Experiment class : Low+High throughput
Enhancer type: Enhancer
Disease: Breast cancer
Pubmed ID:  28378740
Enhancer experiment: ChIP-seq,Luciferase Reporter Assay
Enhancer experiment description: 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 (E19) 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. 2ac).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).

About Target gene

Target gene : CD47(IAP,MER6,OA3)
Strong evidence: --
Less strong evidence: ChIP-seq,Luciferase Reporter Assay
Target gene experiment description: To validate their function experimentally, we cloned each candidate CD47 enhancer (E19) 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. 2ac).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).

About TF

TF name : NFKB1(CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NFKB-p105,NFKB-p50,NFkappaB,p105,p50)
TF experiment: shRNA
TF experiment description: 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?PPAR??(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.

About Function

Enhancer function : --
Enhancer function experiment: --
Enhancer function
experiment description:		 --

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
NFKB1 Activation of NF-kappaB in B cells reactome 66
NFKB1 Alternative NF-kappaB pathway pid 6
NFKB1 amb2 Integrin signaling pid 32
NFKB1 Angiopoietin receptor Tie2-mediated signaling pid 50
NFKB1 Apoptosis signaling pathway panther 104
NFKB1 Atypical NF-kappaB pathway pid 14
NFKB1 BCR netpath 161
NFKB1 BCR signaling pathway pid 70
NFKB1 Canonical NF-kappaB pathway pid 24
NFKB1 CD209 (DC-SIGN) signaling reactome 21
NFKB1 CD40/CD40L signaling pid 36
NFKB1 Ceramide signaling pathway pid 49
NFKB1 CLEC7A (Dectin-1) signaling reactome 78
NFKB1 CLEC7A/inflammasome pathway reactome 6
NFKB1 DEx/H-box helicases activate type I IFN and inflammatory cytokines production reactome 13
NFKB1 Downstream TCR signaling reactome 101
NFKB1 EGFR1 netpath 475
NFKB1 EPO signaling pathway pid 33
NFKB1 Fc-epsilon receptor I signaling in mast cells pid 64
NFKB1 FCERI mediated NF-kB activation reactome 88
NFKB1 Glucocorticoid receptor regulatory network pid 85
NFKB1 HIV-1 Nef: Negative effector of Fas and TNF-alpha pid 33
NFKB1 IkBA variant leads to EDA-ID reactome 7
NFKB1 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) reactome 8
NFKB1 IKK-NF-kappaB cascade ( B cell receptor signaling ) inoh 8
NFKB1 IKK-NF-kappaB cascade ( CD4 T cell receptor signaling (NF-kB cascade) ) inoh 8
NFKB1 IKK-NF-kappaB cascade ( CD4 T cell receptor signaling ) inoh 8
NFKB1 IKK-NFkB cascade ( TNFR1 signaling pathway ) inoh 11
NFKB1 IL1-mediated signaling events pid 34
NFKB1 IL1 netpath 69
NFKB1 IL12-mediated signaling events pid 62
NFKB1 IL2 netpath 81
NFKB1 IL2 signaling events mediated by PI3K pid 38
NFKB1 IL23-mediated signaling events pid 37
NFKB1 IL3 netpath 84
NFKB1 IL4 netpath 75
NFKB1 IL5 netpath 59
NFKB1 IL6 netpath 85
NFKB1 Interleukin-1 processing reactome 7
NFKB1 Intracellular Signalling Through Adenosine Receptor A2a and Adenosine smpdb 37
NFKB1 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine smpdb 38
NFKB1 Leptin netpath 98
NFKB1 LPA receptor mediated events pid 65
NFKB1 MAP3K8 (TPL2)-dependent MAPK1/3 activation reactome 16
NFKB1 NF-kB is activated and signals survival reactome 13
NFKB1 NF-kB signaling ( Toll-like receptor signaling pathway (trough NF-kappaB) ) inoh 12
NFKB1 Notch netpath 76
NFKB1 Osteopontin-mediated events pid 32
NFKB1 Prolactin netpath 105
NFKB1 RANKL netpath 84
NFKB1 Regulated proteolysis of p75NTR reactome 10
NFKB1 Regulation of Telomerase pid 70
NFKB1 RIP-mediated NFkB activation via ZBP1 reactome 21
NFKB1 Senescence-Associated Secretory Phenotype (SASP) reactome 108
NFKB1 Signaling events mediated by HDAC Class I pid 89
NFKB1 T cell receptor signaling (PLC gamma, PKC, Ras and IKK-NF-kappaB cascade) ( CD4 T cell receptor signaling (NF-kB cascade) ) inoh 30
NFKB1 T cell receptor signaling pathway ( CD4 T cell receptor signaling ) inoh 33
NFKB1 TAK1 activates NFkB by phosphorylation and activation of IKKs complex reactome 26
NFKB1 TCR netpath 261
NFKB1 TGF_beta_Receptor netpath 220
NFKB1 TNF receptor signaling pathway pid 46
NFKB1 TNFalpha netpath 274
NFKB1 TRAF6 mediated NF-kB activation reactome 24
NFKB1 Transcriptional regulation of white adipocyte differentiation reactome 79
NFKB1 TSLP netpath 24
NFKB1 TWEAK netpath 35
NFKB1 MAPK signaling pathway kegg 264
NFKB1 Chemokine signaling pathway kegg 187
NFKB1 Apoptosis kegg 88
NFKB1 Toll-like receptor signaling pathway kegg 100
NFKB1 NOD-like receptor signaling pathway kegg 60
NFKB1 RIG-I-like receptor signaling pathway kegg 71
NFKB1 Cytosolic DNA-sensing pathway kegg 56
NFKB1 T cell receptor signaling pathway kegg 105
NFKB1 B cell receptor signaling pathway kegg 70
NFKB1 Neurotrophin signaling pathway kegg 126
NFKB1 Adipocytokine signaling pathway kegg 65
NFKB1 Epithelial cell signaling in Helicobacter pylori infection kegg 67
NFKB1 Shigellosis kegg 60
NFKB1 Leishmaniasis kegg 71
NFKB1 Chagas disease kegg 103
NFKB1 Toxoplasmosis kegg 131
NFKB1 Amoebiasis kegg 103
NFKB1 Hepatitis C kegg 134
NFKB1 Pathways in cancer kegg 321
NFKB1 Pancreatic cancer kegg 70
NFKB1 Prostate cancer kegg 85
NFKB1 Chronic myeloid leukemia kegg 69
NFKB1 Acute myeloid leukemia kegg 53
NFKB1 Small cell lung cancer kegg 83
NFKB1 Hs_Apoptosis-related_network_due_to_altered_Notch3_in_ovarian_cancer_WP2864_79278 wikipathways 51
NFKB1 Hs_Corticotropin-releasing_hormone_signaling_pathway_WP2355_90017 wikipathways 41
NFKB1 Hs_Factors_and_pathways_affecting_insulin-like_growth_factor_(IGF1)-Akt_signaling_WP3850_88165 wikipathways 19
NFKB1 Hs_Leptin_signaling_pathway_WP2034_89856 wikipathways 37
NFKB1 Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
NFKB1 Hs_Apoptosis_Modulation_and_Signaling_WP1772_91293 wikipathways 71
NFKB1 Hs_Structural_Pathway_of_Interleukin_1_(IL-1)_WP2637_87707 wikipathways 34
NFKB1 Hs_Oncostatin_M_Signaling_Pathway_WP2374_73668 wikipathways 44
NFKB1 Hs_TNF_related_weak_inducer_of_apoptosis_(TWEAK)_Signaling_Pathway_WP2036_89910 wikipathways 27
NFKB1 Hs_Apoptosis_Modulation_by_HSP70_WP384_67054 wikipathways 10
NFKB1 Hs_Glucocorticoid_&_Mineralcorticoid_Metabolism_WP237_78497 wikipathways 14
NFKB1 Hs_Allograft_Rejection_WP2328_90020 wikipathways 12
NFKB1 Hs_Oxidative_Damage_WP3941_90810 wikipathways 12
NFKB1 Hs_T-Cell_Receptor_and_Co-stimulatory_Signaling_WP2583_86147 wikipathways 11
NFKB1 Hs_MicroRNAs_in_cardiomyocyte_hypertrophy_WP1544_89794 wikipathways 29
NFKB1 Hs_TNF_alpha_Signaling_Pathway_WP231_89895 wikipathways 61
NFKB1 Hs_IL17_signaling_pathway_WP2112_89838 wikipathways 20
NFKB1 Hs_Estrogen_signaling_pathway_WP712_78491 wikipathways 13
NFKB1 Hs_Gene_regulatory_network_modelling_somitogenesis_WP2854_87527 wikipathways 12
NFKB1 Hs_TLR4_Signaling_and_Tolerance_WP3851_90114 wikipathways 8
NFKB1 Hs_IL1_and_megakaryocytes_in_obesity_WP2865_88662 wikipathways 5
NFKB1 Hs_NAD_metabolism,_sirtuins_and_aging_WP3630_88178 wikipathways 8
NFKB1 Hs_Prolactin_Signaling_Pathway_WP2037_90015 wikipathways 52
NFKB1 Hs_AGE-RAGE_pathway_WP2324_89798 wikipathways 27
NFKB1 Hs_IL-4_Signaling_Pathway_WP395_89828 wikipathways 41
NFKB1 Hs_Brain-Derived_Neurotrophic_Factor_(BDNF)_signaling_pathway_WP2380_89803 wikipathways 80
NFKB1 Hs_T-Cell_antigen_Receptor_(TCR)_Signaling_Pathway_WP69_89937 wikipathways 60
NFKB1 Hs_IL-1_signaling_pathway_WP195_89932 wikipathways 34
NFKB1 Hs_RANKL-RANK_(Receptor_activator_of_NFKB_(ligand))_Signaling_Pathway_WP2018_90016 wikipathways 26
NFKB1 Hs_B_Cell_Receptor_Signaling_Pathway_WP23_89900 wikipathways 71

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