BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

Zeynab Najafova, Roberto Tirado-Magallanes, Malayannan Subramaniam, Tareq Hossan, Geske Schmidt, Sankari Nagarajan, Simon J. Baumgart, Vivek Kumar Mishra, Upasana Bedi, Eric Hesse, Stefan Knapp, John R Hawse, Steven Johnsen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.

Original languageEnglish (US)
Pages (from-to)127-141
Number of pages15
JournalNucleic Acids Research
Volume45
Issue number1
DOIs
StatePublished - 2017

Fingerprint

Transcription Factors
Proteins
Osteoblasts
Genes
Gene Expression
Gene Expression Regulation
Epigenomics
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. / Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J.; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R; Johnsen, Steven.

In: Nucleic Acids Research, Vol. 45, No. 1, 2017, p. 127-141.

Research output: Contribution to journalArticle

Najafova, Z, Tirado-Magallanes, R, Subramaniam, M, Hossan, T, Schmidt, G, Nagarajan, S, Baumgart, SJ, Mishra, VK, Bedi, U, Hesse, E, Knapp, S, Hawse, JR & Johnsen, S 2017, 'BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire', Nucleic Acids Research, vol. 45, no. 1, pp. 127-141. https://doi.org/10.1093/nar/gkw826
Najafova Z, Tirado-Magallanes R, Subramaniam M, Hossan T, Schmidt G, Nagarajan S et al. BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. Nucleic Acids Research. 2017;45(1):127-141. https://doi.org/10.1093/nar/gkw826
Najafova, Zeynab ; Tirado-Magallanes, Roberto ; Subramaniam, Malayannan ; Hossan, Tareq ; Schmidt, Geske ; Nagarajan, Sankari ; Baumgart, Simon J. ; Mishra, Vivek Kumar ; Bedi, Upasana ; Hesse, Eric ; Knapp, Stefan ; Hawse, John R ; Johnsen, Steven. / BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 1. pp. 127-141.
@article{1db72be430c14098a4431dee54d5d53c,
title = "BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire",
abstract = "Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.",
author = "Zeynab Najafova and Roberto Tirado-Magallanes and Malayannan Subramaniam and Tareq Hossan and Geske Schmidt and Sankari Nagarajan and Baumgart, {Simon J.} and Mishra, {Vivek Kumar} and Upasana Bedi and Eric Hesse and Stefan Knapp and Hawse, {John R} and Steven Johnsen",
year = "2017",
doi = "10.1093/nar/gkw826",
language = "English (US)",
volume = "45",
pages = "127--141",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

AU - Najafova, Zeynab

AU - Tirado-Magallanes, Roberto

AU - Subramaniam, Malayannan

AU - Hossan, Tareq

AU - Schmidt, Geske

AU - Nagarajan, Sankari

AU - Baumgart, Simon J.

AU - Mishra, Vivek Kumar

AU - Bedi, Upasana

AU - Hesse, Eric

AU - Knapp, Stefan

AU - Hawse, John R

AU - Johnsen, Steven

PY - 2017

Y1 - 2017

N2 - Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.

AB - Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4.

UR - http://www.scopus.com/inward/record.url?scp=85016016631&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016016631&partnerID=8YFLogxK

U2 - 10.1093/nar/gkw826

DO - 10.1093/nar/gkw826

M3 - Article

C2 - 27651452

AN - SCOPUS:85016016631

VL - 45

SP - 127

EP - 141

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 1

ER -