|
| Status |
Public on Jul 10, 2014 |
| Title |
Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The estrogen receptor-α (ERα) is a transcription factor which plays a critical role in controlling cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to induce or repress gene transcription. A deeper understanding of these transcriptional mechanisms may uncover novel therapeutic targets for ERα-dependent cancers. Here we show for the first time that BRD4 regulates ERα−induced gene expression by affecting elongation-associated phosphorylation of RNA Polymerase II (RNAPII P-Ser2) and histone H2B monoubiquitination (H2Bub1). Consistently, BRD4 activity is required for estrogen-induced proliferation of ER+ breast and endometrial cancer cells and uterine growth in mice. Genome-wide occupancy studies revealed an enrichment of BRD4 on transcriptional start sites as well as EREs enriched for H3K27ac and demonstrate a requirement for BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we further demonstrate that BRD4 occupancy correlates with active mRNA transcription and is required for the production of ERα-dependent enhancer RNAs (eRNAs). These results uncover BRD4 as a central regulator of ERα function and potential therapeutic target.
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| |
|
| Overall design |
ChIP-sequencing of BRD4, ERα and H2Bub1 in MCF7 cells treated with +/- estrogen treatment and or +/- JQ1 treatment in triplicates.
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| |
|
| Contributor(s) |
Nagarajan S, Alawi M, Johnsen SA |
| Citation(s) |
25017071 |
| Submission date |
Mar 14, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Steven A Johnsen |
| E-mail(s) |
sjohnsen@alumni.mayo.edu
|
| Organization name |
University Medical Center Göttingen
|
| Department |
Department of General, Visceral and Pediatric Surgery
|
| Street address |
Robert-Koch-Straße 40
|
| City |
Göttingen |
| State/province |
Niedersachsen |
| ZIP/Postal code |
37075 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (26)
|
|
| This SubSeries is part of SuperSeries: |
| GSE55923 |
Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation |
|
| Relations |
| BioProject |
PRJNA241318 |
| SRA |
SRP040135 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE55921_rphm_normalized_BRD4_E2.wig.gz |
334.8 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_BRD4_Veh.wig.gz |
676.9 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_ER_E2.wig.gz |
584.8 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_ER_JQ1_E2.wig.gz |
563.7 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_H2Bub1_E2.wig.gz |
626.6 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_H2Bub1_JQ1_E2.wig.gz |
598.8 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_H2Bub1_JQ1_Veh.wig.gz |
619.9 Mb |
(ftp)(http) |
WIG |
| GSE55921_rphm_normalized_H2Bub1_Veh.wig.gz |
606.3 Mb |
(ftp)(http) |
WIG |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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