MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

Mayssa H. Mokalled, Aaron N. Johnson, Esther E. Creemers, Eric N. Olson

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR andMRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury andmuscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process.

Original languageEnglish
Pages (from-to)190-202
Number of pages13
JournalGenes and Development
Volume26
Issue number2
DOIs
StatePublished - Jan 15 2012
Externally publishedYes

Keywords

  • MASTR
  • MEF2
  • MRTF-A
  • Muscle regeneration
  • MyoD
  • Satellite cells

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