BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire
2017 | journal article. A publication with affiliation to the University of Göttingen.
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BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire
Najafova, Z.; Tirado-Magallanes, R.; Subramaniam, M.; Hossan, T.; Schmidt, G.; Nagarajan, S. & Baumgart, S. J. et al. (2017)
Nucleic Acids Research, 45(1) pp. 127-141. DOI: https://doi.org/10.1093/nar/gkw826
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Details
- Authors
- 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 A.
- 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.
- Issue Date
- 2017
- Status
- published
- Publisher
- Oxford Univ Press
- Journal
- Nucleic Acids Research
- ISSN
- 1362-4962; 0305-1048