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SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm.
Stashi, Erin; Lanz, Rainer B; Mao, Jianqiang; Michailidis, George; Zhu, Bokai; Kettner, Nicole M; Putluri, Nagireddy; Reineke, Erin L; Reineke, Lucas C; Dasgupta, Subhamoy; Dean, Adam; Stevenson, Connor R; Sivasubramanian, Natarajan; Sreekumar, Arun; Demayo, Francesco; York, Brian; Fu, Loning; O'Malley, Bert W.
Afiliación
  • Stashi E; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Lanz RB; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Mao J; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Michailidis G; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Statistics, University of Michigan, 500 South State Street, Ann Arbor, MI 48109, USA.
  • Zhu B; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Kettner NM; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Putluri N; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Reineke EL; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Reineke LC; Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza Houston, TX 77030, USA.
  • Dasgupta S; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Dean A; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Stevenson CR; Department of Biochemistry and Molecular Biology, Trinity University, One Trinity Place, San Antonio, TX 78212-7200, USA.
  • Sivasubramanian N; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Sreekumar A; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Demayo F; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • York B; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Fu L; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • O'Malley BW; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: berto@bcm.edu.
Cell Rep ; 6(4): 633-45, 2014 Feb 27.
Article en En | MEDLINE | ID: mdl-24529706
Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circadian clock.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ritmo Circadiano / Coactivador 2 del Receptor Nuclear / Metaboloma Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ritmo Circadiano / Coactivador 2 del Receptor Nuclear / Metaboloma Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos