Bromodomain Protein BRD4 Is Required for Estrogen Receptor-Dependent Enhancer Activation and Gene Transcription

Sankari Nagarajan, Tareq Hossan, Malik Alawi, Zeynab Najafova, Daniela Indenbirken, Upasana Bedi, Hanna Taipaleenmäki, Isabel Ben-batalla, Marina Scheller, Sonja Loges, Stefan Knapp, Eric Hesse, Cheng-ming Chiang, Adam Grundhoff, Steven a. Johnsen

Research output: Contribution to journalArticlepeer-review


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 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 ERα-dependent enhancer RNAs. These results uncover BRD4 as a central regulator of ERα function and potential therapeutic target.
Original languageEnglish
Pages (from-to)460-469
JournalCell Reports
Issue number2
Publication statusPublished - 1 Jul 2014


Dive into the research topics of 'Bromodomain Protein BRD4 Is Required for Estrogen Receptor-Dependent Enhancer Activation and Gene Transcription'. Together they form a unique fingerprint.

Cite this