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Mol Cell. 2003 Nov;12(5):1137-49.

Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha.

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  • 1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.

Abstract

Transcriptional coactivators showing physical and functional interactions with PPARgamma include the protein acetyl transferase p300, the TRAP/Mediator complex that interacts with the general transcription machinery, and the highly regulated PGC-1alpha. We show that PGC-1alpha directly interacts with TRAP/Mediator, through the PPARgamma-interacting subunit TRAP220, and stimulates TRAP/Mediator-dependent function on DNA templates. Further, while ineffective by itself, PGC-1alpha stimulates p300-dependent histone acetylation and transcription on chromatin templates in response to PPARgamma. These functions are mediated by largely independent PPARgamma, p300, and TRAP220 interaction domains in PGC-1alpha, whereas p300 and TRAP220 show ligand-dependent interactions with a common region of PPARgamma. Apart from showing PGC-1alpha functions both in chromatin remodeling and in preinitiation complex formation or function (transcription), these results suggest a key role for PGC-1alpha, through concerted but dynamic interactions, in coordinating these steps.

PMID:
14636573
[PubMed - indexed for MEDLINE]
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