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

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.

Source: Nucleic Acids Research - January 8, 2017 Category: Research Authors: 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. Tags: Gene regulation, Chromatin and Epigenetics Source Type: research