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.
Wallberg
Annika E
AE
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
Yamamura
Soichiro
S
Malik
Sohail
S
Spiegelman
Bruce M
BM
Roeder
Robert G
RG
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D050881:E1A-Associated p300 Protein; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; C113182:DRIP, VDR interacting protein complex; C538855:MED1 protein, human; C491863:MED4 protein, human; C538856:Med1 protein, mouse; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse