Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 1, Pages 127-141Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw826
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Funding
- German Academic Exchange Service (DAAD)
- EpiGeneSys consortium travel grant
- Erasmus Mundus External Cooperation Window EURINDIA
- Gottingen Graduate School for Neurosciences, Biophysics and Molecular Biosciences
- German Research Foundation (DFG) [JO 815/3-1]
- Deutsche Krebshilfe [111600]
- German Ministry for Science and Education (BMBF)
- Agence Nationale de la Recherche-iBONE consortium [01KU1401A, 01KU1401B, ANR-14-CE11-0006]
- German Research Foundation [HE 5208/2-1]
- NIH [DE14036]
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE014036] Funding Source: NIH RePORTER
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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.
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