Concerted regulation of myofiber-specific gene expression and muscle performance by the transcriptional repressor Sox6

Daniel Quiat, Kevin A. Voelker, Jimin Pei, Nick V. Grishin, Robert W. Grange, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

In response to physiological stimuli, skeletal muscle alters its myofiber composition to significantly affect muscle performance and metabolism. This process requires concerted regulation of myofiber-specific isoforms of sarcomeric and calcium regulatory proteins that couple action potentials to the generation of contractile force. Here, we identify Sox6 as a fast myofiber-enriched repressor of slow muscle gene expression in vivo. Mice lacking Sox6 specifically in skeletal muscle have an increased number of slow myofibers, elevated mitochondrial activity, and exhibit down-regulation of the fast myofiber gene program, resulting in enhanced muscular endurance. In addition, microarray profiling of Sox6 knockout muscle revealed extensive muscle fiber-type remodeling, and identified numerous genes that display distinctive fiber-type enrichment. Sox6 directly represses the transcription of slow myofiber-enriched genes by binding to conserved cis-regulatory elements. These results identify Sox6 as a robust regulator of muscle contractile phenotype and metabolism, and elucidate a mechanism by which functionally related muscle fiber-type specific gene isoforms are collectively controlled.

Original languageEnglish (US)
Pages (from-to)10196-10201
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number25
DOIs
StatePublished - Jun 21 2011

Keywords

  • Calcium handling
  • Myosin heavy-chain isoforms
  • Slow-twitch fiber

ASJC Scopus subject areas

  • General

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