|
| Status |
Public on Oct 26, 2020 |
| Title |
BET inhibition disrupts transcription but retains enhancer-promoter contact [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes in higher eukaryotes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. Bromodomain and Extra-Terminal domain (BET) and Mediator proteins have been shown capable of forming phase condensates and are thought to be essential for super-enhancer function. Here, we show that targeting of cells with inhibitors of BET proteins or pharmacological degradation of BET protein Bromodomain-containing protein 4 (BRD4) has a strong impact on transcription but very little impact on enhancer-promoter interactions. Dissolving phase condensates reduces BRD4 and Mediator binding at enhancers and can also strongly affect gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further indicate that enhancer-promoter interactions are not dependent on high levels of BRD4 and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and, at some sites, CTCF and cohesin.
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| |
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| Overall design |
ChIP-seq
|
| |
|
| Contributor(s) |
Crump NT, Milne TA |
| Citation(s) |
33431820 |
| |
| Submission date |
Oct 27, 2019 |
| Last update date |
Jan 13, 2021 |
| Contact name |
Thomas A Milne |
| E-mail(s) |
thomas.milne@imm.ox.ac.uk
|
| Organization name |
University of Oxford
|
| Department |
MRC Weatherall Institute of Molecular Medicine
|
| Street address |
John Radcliffe Hospital, Headington
|
| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
| |
|
| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (29)
|
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| This SubSeries is part of SuperSeries: |
| GSE139437 |
BET inhibition disrupts transcription but retains enhancer-promoter contact |
|
| Relations |
| BioProject |
PRJNA579832 |
| SRA |
SRP227131 |
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