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

Journal article

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.

Authors: Najafova, Z; Tirado-Magallanes, R; Subramaniam, M; Hossan, T; Schmidt, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Nucleic Acids Research
• Volume: 45
• Issue: 1
• Pages: 127-141
• Publication date: 2016-09-19
• Acceptance date: 2016-09-08
• DOI: 10.1093/nar/gkw826
• EISSN: 1362-4962
• ISSN: 0305-1048
• Language: English