@article{47dfd36696cc4dfc8a6391f83482b5a9,
title = "Bromodomain Protein BRD4 Is Required for Estrogen Receptor-Dependent Enhancer Activation and Gene Transcription",
abstract = "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 phosphorylationof RNA polymerase II (RNAPII) and histone H2Bmonoubiquitination. Consistently, BRD4 activity isrequired 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.",
author = "Sankari Nagarajan and Tareq Hossan and Malik Alawi and Zeynab Najafova and Daniela Indenbirken and Upasana Bedi and Hanna Taipaleenm{\"a}ki and Isabel Ben-Batalla and Marina Scheller and Sonja Loges and Stefan Knapp and Eric Hesse and Chiang, {Cheng Ming} and Adam Grundhoff and Johnsen, {Steven A.}",
note = "Funding Information: The authors thank G. Salinas-Riester for performing RNA-seq, F. Kramer, T. Beissbarth, and S. Joosse for help in statistical analysis, W.L. Kraus for the list of RNAPII groups, members of the S.A.J. group for thoughtful discussions, and V. Manickam for help with graphic design. This work was funded by the German Academic Exchange Service (to S.N.); the SGC, a registered charity (1097737) that receives funds from the Canadian Institutes for Health Research, the Canada Foundation for Innovation, Genome Canada, AbbVie, Boehringer Ingelheim, Bayer, Janssen, GlaxoSmithKline, Pfizer, Eli Lilly, the Novartis Research Foundation, Takeda, the Ontario Ministry of Research and Innovation, and the Wellcome Trust (092309/Z/10/Z to S.K.); NIH (CA103867), CPRIT (RP110471), and Welch Foundation (I-1805) (to C.-M.C.); German Research Foundation HE 5208/2-1 (to E.H.); the Alexander-von-Humboldt Foundation and EMBO (to H.T.); and the Deutsche Krebshilfe (109088 to S.A.J.). ",
year = "2014",
month = jul,
day = "24",
doi = "10.1016/j.celrep.2014.06.016",
language = "English (US)",
volume = "8",
pages = "460--469",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}