About Enhancer

Enhancer ID: E_02_0889
Species: human
Position : chr7:94002773-94005073
Biosample name:
Experiment class : Low throughput
Enhancer type: Enhancer
Disease: Systemic sclerosis
Pubmed ID:  25303440
Enhancer experiment: Luciferase Reporter Assay
Enhancer experiment description: TGF? is a potent inducer of the human procollagen type I ?2 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 TGF?. 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 T?RE in the FUE region. The results indicated that the COL1A2-FUE was activated by TGF? in both normal and scleroderma fibroblasts.

About Target gene

Target gene : COL1A2(EDSARTH2,EDSCV,OI4)
Strong evidence: --
Less strong evidence: Luciferase Reporter Assay,EMSA,ChIP,siRNA
Target gene experiment description: 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.

About TF

TF name : JUNB(AP-1)JUND(AP-1)
TF experiment: EMSA,ChIP
TF experiment description: 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.

About Function

Enhancer function : Binding of JunB to the COL1A2 enhancer was observed, with its coalescence directed by activation of gene transcription through the proximal promoter.
Enhancer function experiment: ChIP
Enhancer function
experiment description:
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.

About SNP

SNP ID: --

Upstream Pathway Annotation of TF

GeneName Pathway Name Source Gene Number
JUNB AP-1 transcription factor network pid 71
JUNB ATF-2 transcription factor network pid 59
JUNB BCR netpath 161
JUNB Calcineurin-regulated NFAT-dependent transcription in lymphocytes pid 50
JUNB Calcium signaling in the CD4+ TCR pathway pid 29
JUNB Downstream signaling in nave CD8+ T cells pid 69
JUNB IL6-mediated signaling events pid 48
JUNB Inflammation mediated by chemokine and cytokine signaling pathway panther 189
JUNB SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription reactome 32
JUNB TGF-beta signaling pathway panther 88
JUNB TGF_beta_Receptor netpath 220
JUNB TNFalpha netpath 274
JUNB Validated transcriptional targets of AP1 family members Fra1 and Fra2 pid 37
JUNB Hs_Kit_receptor_signaling_pathway_WP304_78799 wikipathways 46
JUNB Hs_TGF-beta_Signaling_Pathway_WP366_90028 wikipathways 67
JUND AP-1 transcription factor network pid 71
JUND ATF-2 transcription factor network pid 59
JUND EGFR1 netpath 475
JUND Inflammation mediated by chemokine and cytokine signaling pathway panther 189
JUND PDGFR-beta signaling pathway pid 125
JUND TGF-beta signaling pathway panther 88
JUND TGF_beta_Receptor netpath 220
JUND Validated transcriptional targets of AP1 family members Fra1 and Fra2 pid 37
JUND MAPK signaling pathway kegg 264
JUND Hs_Apoptosis-related_network_due_to_altered_Notch3_in_ovarian_cancer_WP2864_79278 wikipathways 51
JUND Hs_VEGFA-VEGFR2_Signaling_Pathway_WP3888_90000 wikipathways 153
JUND Hs_Oncostatin_M_Signaling_Pathway_WP2374_73668 wikipathways 44
JUND Hs_EGF-EGFR_Signaling_Pathway_WP437_79266 wikipathways 107

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