BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire.
Nucleic Acids Res
; 45(1): 127-141, 2017 01 09.
Article
in En
| MEDLINE
| ID: mdl-27651452
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoblasts
/
Osteocytes
/
Transcription Factors
/
Nuclear Proteins
/
Cell Lineage
/
Epigenesis, Genetic
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Epithelial Cells
/
Mesenchymal Stem Cells
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2017
Type:
Article
Affiliation country:
Germany