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Series GSE55921 Query DataSets for GSE55921
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.
Overall design ChIP-sequencing of BRD4, ERα and H2Bub1 in MCF7 cells treated with +/- estrogen treatment and or +/- JQ1 treatment in triplicates.
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
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)
GSM1348515 BRD4 Veh rep1
GSM1348516 BRD4 Veh rep2
GSM1348517 BRD4 Veh rep3
This SubSeries is part of SuperSeries:
GSE55923 Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation
BioProject PRJNA241318
SRA SRP040135

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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
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Raw data are available in SRA
Processed data are available on Series record

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