Najafova, ZeynabTirado-Magallanes, RobertoSubramaniam, MalayannanHossan, TareqSchmidt, GeskeNagarajan, SankariBaumgart, Simon J.Mishra, Vivek KumarBedi, UpasanaHess, EricKnapp, StefanHawse, John R.Johnsen, Steven A.2017-05-022017-05-022017-01-09Najafova, Z., Tirado-Magallanes, R., Subramaniam, M., Hossan, T., Schmidt, G., Nagarajan, S., … 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. http://doi.org/10.1093/nar/gkw826https://hdl.handle.net/1805/12422Proper 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.en-USPublisher PolicyBromodomain-containing Protein-4 (BRD4)GenesGene expressionOsteoblast differentiationArticle