About Enhancer

Enhancer ID: E_01_0797
Species: human
Position : chr12:50760530-50762530
Biosample name:
Experiment class : High+Lowthroughput
Enhancer type: Enhancer
Disease: Colorectal cancer (crc)
Pubmed ID:  30026326
Enhancer experiment: ATF1 ChIP-seq,PCR
Enhancer experiment description: 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.

About Target gene

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

About TF

TF name : ATF1TCF7L2MYC(MRTLC,bHLHe39,c-Myc,MYC)BRAF
TF experiment: ATF1 ChIP-seq,PCR
TF experiment description: 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.

About Function

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

About SNP

SNP ID: rs111169571,rs138649767,rs6983267

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
ATF1 CREB phosphorylation reactome 7
ATF1 EGFR1 netpath 475
ATF1 ErbB1 downstream signaling pid 105
ATF1 IL3 netpath 84
ATF1 Leptin netpath 98
ATF1 Signaling mediated by p38-alpha and p38-beta pid 35
ATF1 Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
ATF1 Hs_Serotonin_Receptor_4-6-7_and_NR3C_Signaling_WP734_74438 wikipathways 15
ATF1 Hs_Integrated_Cancer_Pathway_WP1971_82939 wikipathways 33
ATF1 Hs_EGF-EGFR_Signaling_Pathway_WP437_79266 wikipathways 107
TCF7L2 Alzheimer disease-presenilin pathway panther 98
TCF7L2 Angiogenesis panther 141
TCF7L2 AP-1 transcription factor network pid 71
TCF7L2 Binding of TCF/LEF:CTNNB1 to target gene promoters reactome 7
TCF7L2 Ca2+ pathway reactome 62
TCF7L2 Cadherin signaling pathway panther 147
TCF7L2 Canonical Wnt signaling pathway ( C. elegans endoderm induction Wnt signaling pathway Diagram ) inoh 56
TCF7L2 Canonical Wnt signaling pathway ( Canonical Wnt signaling pathway Diagram ) inoh 56
TCF7L2 Canonical Wnt signaling pathway ( Drosophila Wingless/Wnt signaling pathway Diagram ) inoh 56
TCF7L2 Canonical Wnt signaling pathway ( Mammalian Wnt signaling pathway Diagram ) inoh 56
TCF7L2 Canonical Wnt signaling pathway ( Xenopus axis formation Wnt signaling pathway Diagram ) inoh 56
TCF7L2 Deactivation of the beta-catenin transactivating complex reactome 42
TCF7L2 Formation of the beta-catenin:TCF transactivating complex reactome 88
TCF7L2 ID netpath 38
TCF7L2 Mammalian Wnt signaling pathway ( Mammalian Wnt signaling pathway Diagram ) inoh 49
TCF7L2 Regulation of nuclear beta catenin signaling and target gene transcription pid 80
TCF7L2 Repression of WNT target genes reactome 14
TCF7L2 Signaling with Wnt (Canonical) ( C. elegans endoderm induction Wnt signaling pathway Diagram ) inoh 47
TCF7L2 Signaling with Wnt (Canonical) ( Canonical Wnt signaling pathway Diagram ) inoh 47
TCF7L2 Signaling with Wnt (Canonical) ( Drosophila Wingless/Wnt signaling pathway Diagram ) inoh 47
TCF7L2 Signaling with Wnt (Canonical) ( Mammalian Wnt signaling pathway Diagram ) inoh 47
TCF7L2 Signaling with Wnt (Canonical) ( Xenopus axis formation Wnt signaling pathway Diagram ) inoh 47
TCF7L2 Signaling with Wnt (Mammal) ( Mammalian Wnt signaling pathway Diagram ) inoh 47
TCF7L2 Signaling with Wnt (Xenopus) ( Xenopus axis formation Wnt signaling pathway Diagram ) inoh 19
TCF7L2 Signaling without Wnt (Canonical) ( C. elegans endoderm induction Wnt signaling pathway Diagram ) inoh 8
TCF7L2 Signaling without Wnt (Canonical) ( Canonical Wnt signaling pathway Diagram ) inoh 8
TCF7L2 Signaling without Wnt (Canonical) ( Drosophila Wingless/Wnt signaling pathway Diagram ) inoh 8
TCF7L2 Signaling without Wnt (Canonical) ( Mammalian Wnt signaling pathway Diagram ) inoh 8
TCF7L2 Signaling without Wnt (Canonical) ( Xenopus axis formation Wnt signaling pathway Diagram ) inoh 8
TCF7L2 Signaling without Wnt (Mammal) ( Mammalian Wnt signaling pathway Diagram ) inoh 8
TCF7L2 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) reactome 20
TCF7L2 Wnt netpath 118
TCF7L2 Wnt signaling pathway panther 250
TCF7L2 Wnt signaling pathway kegg 135
TCF7L2 Adherens junction kegg 70
TCF7L2 Melanogenesis kegg 100
TCF7L2 Pathways in cancer kegg 321
TCF7L2 Colorectal cancer kegg 63
TCF7L2 Endometrial cancer kegg 52
TCF7L2 Prostate cancer kegg 85
TCF7L2 Acute myeloid leukemia kegg 53
TCF7L2 Arrhythmogenic right ventricular cardiomyopathy (ARVC) kegg 71
MYC AP-1 transcription factor network pid 71
MYC Binding of TCF/LEF:CTNNB1 to target gene promoters reactome 7
MYC C-MYB transcription factor network pid 87
MYC C-MYC pathway pid 25
MYC CD40/CD40L signaling pid 36
MYC Ceramide signaling pathway pid 49
MYC Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants reactome 57
MYC Constitutive Signaling by NOTCH1 PEST Domain Mutants reactome 57
MYC Cyclin A:Cdk2-associated events at S phase entry reactome 15
MYC Cyclin E associated events during G1/S transition reactome 14
MYC E2F transcription factor network pid 77
MYC EGFR1 netpath 475
MYC Formation of the beta-catenin:TCF transactivating complex reactome 88
MYC FOXM1 transcription factor network pid 43
MYC IL2-mediated signaling events pid 54
MYC IL2 signaling events mediated by PI3K pid 38
MYC IL2 signaling events mediated by STAT5 pid 30
MYC IL6-mediated signaling events pid 48
MYC Interleukin signaling pathway panther 86
MYC LKB1 signaling events pid 43
MYC MAPK6/MAPK4 signaling reactome 90
MYC Notch signaling pathway pid 58
MYC NOTCH1 Intracellular Domain Regulates Transcription reactome 47
MYC Oxidative stress response panther 23
MYC p53 pathway feedback loops 2 panther 42
MYC p73 transcription factor network pid 80
MYC PDGF signaling pathway panther 113
MYC PDGFR-beta signaling pathway pid 125
MYC Presenilin action in Notch and Wnt signaling pid 46
MYC Prolactin netpath 105
MYC Regulation of nuclear beta catenin signaling and target gene transcription pid 80
MYC Regulation of nuclear SMAD2/3 signaling pid 82
MYC Regulation of Telomerase pid 70
MYC SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription reactome 32
MYC TGF_beta_Receptor netpath 220
MYC Validated nuclear estrogen receptor alpha network pid 65
MYC Validated targets of C-MYC transcriptional activation pid 80
MYC Validated targets of C-MYC transcriptional repression pid 63
MYC MAPK signaling pathway kegg 264
MYC ErbB signaling pathway kegg 83
MYC Cell cycle kegg 124
MYC Wnt signaling pathway kegg 135
MYC TGF-beta signaling pathway kegg 82
MYC Jak-STAT signaling pathway kegg 149
MYC Pathways in cancer kegg 321
MYC Colorectal cancer kegg 63
MYC Endometrial cancer kegg 52
MYC Thyroid cancer kegg 25
MYC Bladder cancer kegg 38
MYC Chronic myeloid leukemia kegg 69
MYC Acute myeloid leukemia kegg 53
MYC Small cell lung cancer kegg 83
MYC Hs_DNA_Damage_Response_(only_ATM_dependent)_WP710_79974 wikipathways 36
MYC Hs_TP53_Network_WP1742_71700 wikipathways 10
MYC Hs_Imatinib_and_Chronic_Myeloid_Leukemia_WP3640_89384 wikipathways 11
MYC Hs_miRNAs_involved_in_DNA_damage_response_WP1545_84697 wikipathways 30
MYC Hs_Association_Between_Physico-Chemical_Features_and_Toxicity_Associated_Pathways_WP3680_90113 wikipathways 31
MYC Hs_Gastric_Cancer_Network_2_WP2363_87523 wikipathways 28
MYC Hs_Hepatitis_C_and_Hepatocellular_Carcinoma_WP3646_88640 wikipathways 36
MYC Hs_Apoptosis_WP254_88977 wikipathways 31
MYC Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
MYC Hs_Neural_Crest_Differentiation_WP2064_79263 wikipathways 40
MYC Hs_IL-5_Signaling_Pathway_WP127_78498 wikipathways 35
MYC Hs_Prolactin_Signaling_Pathway_WP2037_90015 wikipathways 52
MYC Hs_EGF-EGFR_Signaling_Pathway_WP437_79266 wikipathways 107
MYC Hs_IL-7_Signaling_Pathway_WP205_89854 wikipathways 16
BRAF AKT(PKB)-Bad signaling ( EPO signaling pathway(JAK2 STAT1 STAT3 STAT5) ) inoh 173
BRAF AKT(PKB)-Bad signaling ( IL-7 signaling(JAK1 JAK3 STAT5) ) inoh 173
BRAF Angiogenesis panther 141
BRAF ARMS-mediated activation reactome 7
BRAF BCR netpath 161
BRAF CDC42 signaling events pid 71
BRAF CREB phosphorylation through the activation of Ras reactome 13
BRAF Downstream signaling in nave CD8+ T cells pid 69
BRAF Drosophila Toll-like receptor signaling ( Drosophila Toll-like receptor signaling ) inoh 236
BRAF EGFR1 netpath 475
BRAF ErbB1 downstream signaling pid 105
BRAF ERK cascade ( B cell receptor signaling ) inoh 7
BRAF ERK cascade ( CD4 T cell receptor signaling (ERK cascade) ) inoh 10
BRAF ERK cascade ( CD4 T cell receptor signaling ) inoh 7
BRAF ERK cascade ( FGF signaling pathway ) inoh 8
BRAF ERK cascade ( FGF8 signaling (Mouse) ) inoh 17
BRAF ERK cascade ( FGF8 signaling (Xenopus) ) inoh 17
BRAF ERK cascade ( GPCR Adenosine A2A receptor signaling pathway ) inoh 5
BRAF ERK cascade ( GPCR GroupI metabotropic glutamate receptor signaling pathway ) inoh 7
BRAF ERK cascade ( GPCR signaling (G alpha q) ) inoh 7
BRAF ERK cascade ( GPCR signaling (G alpha s, Epac and ERK) ) inoh 5
BRAF ERK cascade ( IGF1 signaling pathway ) inoh 8
BRAF ERK cascade ( Insulin receptor signaling (D. melanogaster) ) inoh 8
BRAF ERK cascade ( Insulin receptor signaling (Mammal) ) inoh 8
BRAF ERK cascade ( JAK-STAT pathway and regulation pathway Diagram ) inoh 7
BRAF ERK cascade ( NGF signaling pathway ) inoh 8
BRAF FGF signaling pathway ( FGF signaling pathway ) inoh 44
BRAF FGF8 signaling pathway(Mouse) ( FGF8 signaling (Mouse) ) inoh 20
BRAF FGF8 signaling pathway(Xenopus) ( FGF8 signaling (Xenopus) ) inoh 18
BRAF Frs2-mediated activation reactome 9
BRAF Heterotrimeric GPCR signaling pathway (through G alpha q, PLC beta and ERK cascade) ( GPCR signaling (G alpha q) ) inoh 239
BRAF Heterotrimeric GPCR signaling pathway (through glutamate, G alpha q and PLC beta) ( GPCR GroupI metabotropic glutamate receptor signaling pathway ) inoh 18
BRAF IGF1 signaling pathway ( IGF1 signaling pathway ) inoh 27
BRAF Insulin receptor signaling ( Insulin receptor signaling (D. melanogaster) ) inoh 55
BRAF Insulin receptor signaling (Mammal) ( Insulin receptor signaling (Mammal) ) inoh 58
BRAF Integrin signaling pathway ( Integrin signaling pathway ) inoh 123
BRAF Integrin signalling pathway panther 156
BRAF Interleukin signaling pathway panther 86
BRAF Intracellular Signalling Through Adenosine Receptor A2a and Adenosine smpdb 37
BRAF Intracellular Signalling Through Adenosine Receptor A2b and Adenosine smpdb 38
BRAF MAP2K and MAPK activation reactome 38
BRAF mTOR signaling pathway pid 66
BRAF Negative feedback regulation of MAPK pathway reactome 6
BRAF Negative regulation of MAPK pathway reactome 38
BRAF NGF signaling pathway ( NGF signaling pathway ) inoh 16
BRAF PDGF signaling pathway panther 113
BRAF PDGFR-beta signaling pathway pid 125
BRAF Positive regulation of (Transcription of SOCS by STAT dimer) in JAK STAT pathway ( JAK-STAT pathway and regulation pathway Diagram ) inoh 178
BRAF Prolactin netpath 105
BRAF RAF activation reactome 25
BRAF Raf activation signaling (through Grb2 and Sos) ( B cell receptor signaling ) inoh 9
BRAF Raf activation signaling (through Grb2 and Sos) ( CD4 T cell receptor signaling (ERK cascade) ) inoh 9
BRAF Raf activation signaling (through Grb2 and Sos) ( CD4 T cell receptor signaling ) inoh 9
BRAF Raf activation signaling (through Grb2 and Sos) ( JAK-STAT pathway and regulation pathway Diagram ) inoh 9
BRAF Raf activation signaling (through RasGRP) ( CD4 T cell receptor signaling (ERK cascade) ) inoh 8
BRAF Raf activation signaling (through RasGRP) ( CD4 T cell receptor signaling ) inoh 7
BRAF Ras Pathway panther 69
BRAF Ras signaling in the CD4+ TCR pathway pid 14
BRAF Signaling events mediated by focal adhesion kinase pid 63
BRAF Signaling events mediated by VEGFR1 and VEGFR2 pid 69
BRAF Signalling to p38 via RIT and RIN reactome 5
BRAF Spry regulation of FGF signaling reactome 16
BRAF T cell activation panther 60
BRAF Trk receptor signaling mediated by the MAPK pathway pid 34
BRAF VEGF signaling pathway ( VEGF signaling pathway ) inoh 183
BRAF VEGF signaling pathway panther 54
BRAF ERK cascade ( Integrin signaling pathway ) inoh 5
BRAF MAPK signaling pathway kegg 264
BRAF ErbB signaling pathway kegg 83
BRAF Chemokine signaling pathway kegg 187
BRAF mTOR signaling pathway kegg 50
BRAF Vascular smooth muscle contraction kegg 114
BRAF Focal adhesion kegg 197
BRAF Natural killer cell mediated cytotoxicity kegg 125
BRAF Long-term potentiation kegg 67
BRAF Neurotrophin signaling pathway kegg 126
BRAF Long-term depression kegg 67
BRAF Regulation of actin cytoskeleton kegg 210
BRAF Insulin signaling pathway kegg 134
BRAF Hepatitis C kegg 134
BRAF Pathways in cancer kegg 321
BRAF Colorectal cancer kegg 63
BRAF Renal cell carcinoma kegg 65
BRAF Pancreatic cancer kegg 70
BRAF Endometrial cancer kegg 52
BRAF Glioma kegg 65
BRAF Thyroid cancer kegg 25
BRAF Melanoma kegg 69
BRAF Bladder cancer kegg 38
BRAF Chronic myeloid leukemia kegg 69
BRAF Non-small cell lung cancer kegg 54
BRAF Hs_Cell_Cycle_WP179_89516 wikipathways 33
BRAF Hs_Corticotropin-releasing_hormone_signaling_pathway_WP2355_90017 wikipathways 41
BRAF Hs_MAPK_Signaling_Pathway_WP382_79951 wikipathways 58
BRAF Hs_Senescence_and_Autophagy_in_Cancer_WP615_81193 wikipathways 62
BRAF Hs_Integrated_Breast_Cancer_Pathway_WP1984_82941 wikipathways 122
BRAF Hs_Serotonin_Receptor_4-6-7_and_NR3C_Signaling_WP734_74438 wikipathways 15
BRAF Hs_Bladder_Cancer_WP2828_89143 wikipathways 17
BRAF Hs_Estrogen_signaling_pathway_WP712_78491 wikipathways 13
BRAF Hs_EGF-EGFR_Signaling_Pathway_WP437_79266 wikipathways 107
BRAF 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