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

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Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. / Nagarajan, Sankari; Hossan, Tareq; Alawi, Malik; Najafova, Zeynab; Indenbirken, Daniela; Bedi, Upasana; Taipaleenmäki, Hanna; Ben-Batalla, Isabel; Scheller, Marina; Loges, Sonja; Knapp, Stefan; Hesse, Eric; Chiang, Cheng-Ming; Grundhoff, Adam; Johnsen, Steven A.

In: CELL REP, Vol. 8, No. 2, 24.07.2014, p. 459-468.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Nagarajan, S, Hossan, T, Alawi, M, Najafova, Z, Indenbirken, D, Bedi, U, Taipaleenmäki, H, Ben-Batalla, I, Scheller, M, Loges, S, Knapp, S, Hesse, E, Chiang, C-M, Grundhoff, A & Johnsen, SA 2014, 'Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription', CELL REP, vol. 8, no. 2, pp. 459-468. https://doi.org/10.1016/j.celrep.2014.06.016

APA

Nagarajan, S., Hossan, T., Alawi, M., Najafova, Z., Indenbirken, D., Bedi, U., Taipaleenmäki, H., Ben-Batalla, I., Scheller, M., Loges, S., Knapp, S., Hesse, E., Chiang, C-M., Grundhoff, A., & Johnsen, S. A. (2014). Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. CELL REP, 8(2), 459-468. https://doi.org/10.1016/j.celrep.2014.06.016

Vancouver

Nagarajan S, Hossan T, Alawi M, Najafova Z, Indenbirken D, Bedi U et al. Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. CELL REP. 2014 Jul 24;8(2):459-468. https://doi.org/10.1016/j.celrep.2014.06.016

Bibtex

@article{f2086cb1b544429c86f1a17252bccabc,
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 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.",
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 Cheng-Ming Chiang and Adam Grundhoff and Johnsen, {Steven A}",
note = "Copyright {\textcopyright} 2014 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = jul,
day = "24",
doi = "10.1016/j.celrep.2014.06.016",
language = "English",
volume = "8",
pages = "459--468",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription

AU - Nagarajan, Sankari

AU - Hossan, Tareq

AU - Alawi, Malik

AU - Najafova, Zeynab

AU - Indenbirken, Daniela

AU - Bedi, Upasana

AU - Taipaleenmäki, Hanna

AU - Ben-Batalla, Isabel

AU - Scheller, Marina

AU - Loges, Sonja

AU - Knapp, Stefan

AU - Hesse, Eric

AU - Chiang, Cheng-Ming

AU - Grundhoff, Adam

AU - Johnsen, Steven A

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/7/24

Y1 - 2014/7/24

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2014.06.016

DO - 10.1016/j.celrep.2014.06.016

M3 - SCORING: Journal article

C2 - 25017071

VL - 8

SP - 459

EP - 468

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 2

ER -