Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [RNA-Seq]
Transcriptomics Dataset
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General Information
| Accession | GSE55922 |
| Title | Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [RNA-Seq] |
| Description | The estrogen receptor- (ER) 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 ER-dependent cancers. Here we show for the first time that BRD4 regulates ERinduced 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 ER-dependent enhancer RNAs (eRNAs). These results uncover BRD4 as a central regulator of ER function and potential therapeutic target. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55922 |
| Repository | Gene Expression Omnibus |
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