Enhancer ID: | E_02_0767 |
Species: | human |
Position : | chr2:11633299-11641134 |
Biosample name: | |
Experiment class : | Low+High throughput |
Enhancer type: | Enhancer |
Disease: | Breast cancer |
Pubmed ID: | 29378668 |
Enhancer experiment: | ChIP-seq,3C,ChIP-qPCR |
Enhancer experiment description: | Additionally, overlap with datasets containing histone ChIP-Seq data reveals the enrichment of histone marks corresponding to active/poised enhancers and depleted of those markings found at repressed/silenced enhancers.Validations were performed using conventional ChIP-qPCR.Compared to genomic background, global analysis of the high-confidence TDG peaks revealed that E2-dependent TDG binding was enriched at promoters as well as distal to promoters with approximately 60% occurring intergenically.However, overlapping TDG peaks with sites of E2-dependent ER? localization revealed that 45% of TDG peaks occur at the same sites where ER? localizes in response to E2. |
Target gene : | GREB1(GREB1) |
Strong evidence: | 3C |
Less strong evidence: | -- |
Target gene experiment description: | ChIP using ER in the presence and absence of TDG as well as ? or + E2, showing that ER binding is unaltered during depletion of TDG. e Loss of TDG prevents enhancerpromoter looping at the GREB1 locus. MCF7 cells were treated with siControl or siTDG, and then treated with 100 nM E2 for 1 h. 3C, semiquantitative method of measuring the looping between the GREB1 enhancer and promoter, revealed that E2-driven looping of the enhancer and promoter is disrupted upon TDG knockdown. |
TF name : | TDG(hTDG) |
TF experiment: | CRISPR/Cas9 |
TF experiment description: | Remarkably, at a subset of enhancers that E2 targets, we found that TDG depletion abrogates E2-mediated eRNA, disrupts 3-dimensional reorganization at ER-targets such as GREB1 and disrupts E2-mediated transcription of corresponding ER-target genes. To investigate whether TDG plays a functional role in E2 signaling in breast cancer, we engineered an MCF7 TDG knockout cell line using CRISPR technology and found that TDG knockout and depletion leads to defects in E2-mediated proliferation and sensitizes MCF7 cells to the anti-estrogen. |
Enhancer function : | -- |
Enhancer function experiment: | -- |
Enhancer function experiment description: |
-- |
SNP ID: | -- |
GeneName | Pathway Name | Source | Gene Number |
---|---|---|---|
TDG | Cleavage of the damaged pyrimidine | reactome | 8 |
TDG | Displacement of DNA glycosylase by APEX1 | reactome | 9 |
TDG | Recognition and association of DNA glycosylase with site containing an affected pyrimidine | reactome | 8 |
TDG | SUMOylation of DNA damage response and repair proteins | reactome | 76 |