HDAC4 regulates muscle fiber type-specific gene expression programs.
Journal Article (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
- PMC4400309
Electronic International Standard Serial Number (EISSN)
- 0219-1032
Digital Object Identifier (DOI)
- 10.14348/molcells.2015.2278
Language
- eng
Conference Location
- Korea (South)