Unknown

Dataset Information

0

Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription.


ABSTRACT: The estrogen receptor ? (ER?) controls cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to control gene transcription. A deeper understanding of these transcriptional mechanisms may uncover therapeutic targets for ER?-dependent cancers. We show that BRD4 regulates ER?-induced gene expression by affecting elongation-associated phosphorylation of RNA polymerase II (RNAPII) and histone H2B monoubiquitination. Consistently, BRD4 activity is required for proliferation of ER(+) breast and endometrial cancer cells and uterine growth in mice. Genome-wide studies revealed an enrichment of BRD4 on transcriptional start sites of active genes and a requirement of BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we demonstrate that BRD4 occupancy on distal EREs enriched for H3K27ac is required for recruitment and elongation of RNAPII on EREs and the production of ER?-dependent enhancer RNAs. These results uncover BRD4 as a central regulator of ER? function and potential therapeutic target.

SUBMITTER: Nagarajan S 

PROVIDER: S-EPMC4747248 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


The estrogen receptor α (ERα) controls cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to control gene transcription. A deeper understanding of these transcriptional mechanisms may uncover therapeutic targets for ERα-dependent cancers. We show that BRD4 regulates ERα-induced gene expression by affecting elongation-associated phosphorylation of RNA polymerase II (RNAPII) and histone H2B monoubiquitination. Consistently, BRD4 activity is re  ...[more]

Similar Datasets

| S-ECPF-GEOD-55922 | biostudies-other
2014-07-10 | E-GEOD-55923 | biostudies-arrayexpress
2014-07-10 | GSE55923 | GEO
2014-07-10 | E-GEOD-55921 | biostudies-arrayexpress
2014-07-10 | E-GEOD-55922 | biostudies-arrayexpress
2014-07-10 | GSE55922 | GEO
2014-07-10 | GSE55921 | GEO
| S-EPMC5770188 | biostudies-literature
| S-EPMC4147693 | biostudies-literature
| S-EPMC2431025 | biostudies-literature