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 A. Johnsen

Research output: Contribution to journalArticle

31 Scopus citations

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

ASJC Scopus subject areas

  • Genetics

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    Najafova, Z., Tirado-Magallanes, R., Subramaniam, M., Hossan, T., Schmidt, G., Nagarajan, S., Baumgart, S. J., Mishra, V. K., Bedi, U., Hesse, E., Knapp, S., Hawse, J. R., & Johnsen, S. A. (2017). BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. Nucleic acids research, 45(1), 127-141. https://doi.org/10.1093/nar/gkw826