Coordination of p300-Mediated Chromatin Remodeling and TRAP/Mediator Function through Coactivator PGC-1α

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