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

Autor: Wallberg AE; Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA., Yamamura S, Malik S, Spiegelman BM, Roeder RG
Jazyk: angličtina
Zdroj: Molecular cell [Mol Cell] 2003 Nov; Vol. 12 (5), pp. 1137-49.
DOI: 10.1016/s1097-2765(03)00391-5
Abstrakt: 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.
Databáze: MEDLINE