HDAC4 regulates muscle fiber type-specific gene expression programs.

Published

Journal Article

Fiber type-specific programs controlled by the transcription factor MEF2 dictate muscle functionality. Here, we show that HDAC4, a potent MEF2 inhibitor, is predominantly localized to the nuclei in fast/glycolytic fibers in contrast to the sarcoplasm in slow/oxidative fibers. The cytoplasmic localization is associated with HDAC4 hyper-phosphorylation in slow/oxidative-fibers. Genetic reprogramming of fast/glycolytic fibers to oxidative fibers by active CaMKII or calcineurin leads to increased HDAC4 phosphorylation, HDAC4 nuclear export, and an increase in markers associated with oxidative fibers. Indeed, HDAC4 represses the MEF2-dependent, PGC-1α-mediated oxidative metabolic gene program. Thus differential phosphorylation and localization of HDAC4 contributes to establishing fiber type-specific transcriptional programs.

Full Text

Duke Authors

Cited Authors

  • Cohen, TJ; Choi, M-C; Kapur, M; Lira, VA; Yan, Z; Yao, T-P

Published Date

  • April 2015

Published In

Volume / Issue

  • 38 / 4

Start / End Page

  • 343 - 348

PubMed ID

  • 25728750

Pubmed Central ID

  • 25728750

Electronic International Standard Serial Number (EISSN)

  • 0219-1032

Digital Object Identifier (DOI)

  • 10.14348/molcells.2015.2278

Language

  • eng

Conference Location

  • Korea (South)