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  • Title: The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle.
    Author: Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM.
    Journal: Cell Metab; 2007 Jan; 5(1):35-46. PubMed ID: 17189205.
    Abstract:
    Skeletal muscle must perform different kinds of work, and distinct fiber types have evolved to accommodate these. Previous work had shown that the transcriptional coactivator PGC-1alpha drives the formation of type I and IIA muscle fibers, which are "slow-twitch" and highly oxidative. We show here that transgenic expression of PGC-1beta, a coactivator functionally similar to but distinct from PGC-1alpha, causes a marked induction of IIX fibers, which are oxidative but have "fast-twitch" biophysical properties. PGC-1beta coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1beta transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1beta of ERRalpha and PPARalpha. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1beta drives the formation of highly oxidative fibers containing type IIX MHC.
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