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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.
Afiliación
  • Najafova Z; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Tirado-Magallanes R; Institut de Biologie de l'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, F-75005 Paris, France.
  • Subramaniam M; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
  • Hossan T; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Schmidt G; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Nagarajan S; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Baumgart SJ; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Mishra VK; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Bedi U; Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • Hesse E; Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Knapp S; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Hawse JR; Institute for Pharmaceutical Chemistry, Goethe-University Frankfurt, 60323 Frankfurt am Main, Germany.
  • Johnsen SA; Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Oxford OX3 7DQ, UK.
Nucleic Acids Res ; 45(1): 127-141, 2017 01 09.
Article en En | MEDLINE | ID: mdl-27651452
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Osteoblastos / Osteocitos / Factores de Transcripción / Proteínas Nucleares / Linaje de la Célula / Epigénesis Genética / Células Epiteliales / Células Madre Mesenquimatosas Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2017 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Osteoblastos / Osteocitos / Factores de Transcripción / Proteínas Nucleares / Linaje de la Célula / Epigénesis Genética / Células Epiteliales / Células Madre Mesenquimatosas Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2017 Tipo del documento: Article País de afiliación: Alemania