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

Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10196-201. doi: 10.1073/pnas.1107413108. Epub 2011 Jun 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Mice
  • Mice, Knockout
  • Microarray Analysis
  • Muscle Contraction / physiology
  • Muscle Fibers, Fast-Twitch / cytology
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscle Fibers, Slow-Twitch / cytology
  • Muscle Fibers, Slow-Twitch / physiology*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • SOXD Transcription Factors / genetics
  • SOXD Transcription Factors / metabolism*


  • SOXD Transcription Factors
  • Sox6 protein, mouse
  • Calcium