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Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [RNA-Seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55922 | GEO | 2014/07/10

SECONDARY ACCESSION(S): PRJNA241317

REPOSITORIES: GEO

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Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [ChIP-seq]

Project description: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. ChIP-sequencing of BRD4, ERα and H2Bub1 in MCF7 cells treated with +/- estrogen treatment and or +/- JQ1 treatment in triplicates.

2014-07-10 | E-GEOD-55921 | biostudies-arrayexpress

Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [ChIP-seq]

2014-07-10 | GSE55921 | GEO

Bromodomain protein BRD4 is required for estrogen receptor-dependent transcription and enhancer activation [RNA-Seq]

Project description:The estrogen receptor-M-NM-1 (ERM-NM-1) 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 ERM-NM-1-dependent cancers. Here we show for the first time that BRD4 regulates ERM-NM-1M-bM-^HM-^Rinduced 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 ERM-NM-1-dependent enhancer RNAs (eRNAs). These results uncover BRD4 as a central regulator of ERM-NM-1 function and potential therapeutic target. mRNA expression profiles of MCF7 cells treated with +/- estrogen treatment under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.

2014-07-10 | E-GEOD-55922 | biostudies-arrayexpress

H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription

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The SET Oncoprotein Promotes Estrogen-Induced Transcription by Facilitating Establishment of Active Chromatin

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