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Mol Cells. 2015 Apr;38(4):343-8. doi: 10.14348/molcells.2015.2278. Epub 2015 Feb 25.

HDAC4 regulates muscle fiber type-specific gene expression programs.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
2
Department of Neurology, UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
3
Department of Medicine, Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA22908, USA.

Abstract

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.

KEYWORDS:

HDAC4; MEF2; PGC-1α; fiber type

PMID:
25728750
PMCID:
PMC4400309
DOI:
10.14348/molcells.2015.2278
[Indexed for MEDLINE]
Free PMC Article

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