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

Nucleic Acids Research
Zeynab NajafovaSteven A Johnsen

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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Citations

Dec 17, 2016·Nucleic Acids Research·Sankari NagarajanSteven A Johnsen
Jul 29, 2018·American Journal of Medical Genetics. Part a·Laiara Cristina de SouzaTársis Paiva Vieira
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Methods Mentioned

BETA
transfections
immunoprecipitation
ChIP
PCR
RNA-Seq
ChIP-Seq
ChIPs
acetylation

Software Mentioned

Galaxy
HTSeq
Samtools
gplots R package
computeMatrix
UCSC Table Browser
ImageJ
Epigenome Count - based Segmentation ( EpiCSeg )
TopHat Gapped - read mapper
ReMap

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