BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire
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BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. / 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.
in: NUCLEIC ACIDS RES, Jahrgang 45, Nr. 1, 09.01.2017, S. 127-141.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire
AU - Najafova, Zeynab
AU - Tirado-Magallanes, Roberto
AU - Subramaniam, Malayannan
AU - Hossan, Tareq
AU - Schmidt, Geske
AU - Nagarajan, Sankari
AU - Baumgart, Simon J
AU - Mishra, Vivek Kumar
AU - Bedi, Upasana
AU - Hesse, Eric
AU - Knapp, Stefan
AU - Hawse, John R
AU - Johnsen, Steven A
N1 - © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2017/1/9
Y1 - 2017/1/9
N2 - 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.
AB - 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.
U2 - 10.1093/nar/gkw826
DO - 10.1093/nar/gkw826
M3 - SCORING: Journal article
C2 - 27651452
VL - 45
SP - 127
EP - 141
JO - NUCLEIC ACIDS RES
JF - NUCLEIC ACIDS RES
SN - 0305-1048
IS - 1
ER -