Skeletal myosin light chain kinase regulates skeletal myogenesis by phosphorylation of MEF2C

Ashraf Al Madhoun, Virja Mehta, Grace Li, Daniel Figeys, Nadine Wiper-Bergeron, Ilona S. Skerjanc

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The MEF2 factors regulate transcription during cardiac and skeletal myogenesis. MEF2 factors establish skeletal muscle commitment by amplifying and synergizing with MyoD. While phosphorylation is known to regulate MEF2 function, lineage-specific regulation is unknown. Here, we show that phosphorylation of MEF2C on T 80 by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis. A phosphorylation-deficient MEF2C mutant (MEFT80A) enhanced cardiac, but not skeletal myogenesis in P19 stem cells. Further, MEFT80A was deficient in recruitment of p300 to skeletal but not cardiac muscle promoters. In gain-of-function studies, skMLCK upregulated myogenic regulatory factor (MRF) expression, leading to enhanced skeletal myogenesis in P19 cells and more efficient myogenic conversion. In loss-of-function studies, MLCK was essential for efficient MRF expression and subsequent myogenesis in embryonic stem (ES) and P19 cells as well as for proper activation of quiescent satellite cells. Thus, skMLCK regulates MRF expression by controlling the MEF2C-dependent recruitment of histone acetyltransferases to skeletal muscle promoters. This work identifies the first kinase that regulates MyoD and Myf5 expression in ES or satellite cells.

Original languageEnglish
Pages (from-to)2477-2489
Number of pages13
JournalEMBO Journal
Volume30
Issue number12
DOIs
Publication statusPublished - 1 May 2011

Keywords

  • MEF2
  • MRFs
  • skeletal myogenesis
  • skMLCK
  • stem cells

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