Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha.
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.
Pubmed ID: 14636573 RIS Download
Animals | Chromatin | E1A-Associated p300 Protein | Genes, Reporter | HeLa Cells | Humans | Mediator Complex | Mediator Complex Subunit 1 | Mice | Nuclear Proteins | Protein Subunits | Receptors, Cytoplasmic and Nuclear | Recombinant Fusion Proteins | Trans-Activators | Transcription Factors | Transcription, Genetic