BRD4 Localization to Lineage-specific Enhancers is Associated with a Distinct Transcription Factor Repertoire

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 Sep 22

PMID 27651452

Citations 63

Authors

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 A Johnsen

Affiliations

Soon will be listed here.

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.

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