Pax3/7BP is a Pax7- and Pax3-binding protein that regulates the proliferation of muscle precursor cells by an epigenetic mechanism

Cell Stem Cell. 2012 Aug 3;11(2):231-41. doi: 10.1016/j.stem.2012.05.022.

Abstract

In mouse skeletal muscles, Pax7 uniquely marks muscle satellite cells and plays some important yet unknown functions at the perinatal stage. To elucidate its in vivo functions, we initiated a yeast two-hybrid screening to look for Pax7-interacting proteins and identified a previously uncharacterized Pax7- and Pax3-binding protein (Pax3/7BP). Pax3/7BP is a ubiquitously expressed nuclear protein, enriched in Pax7+ muscle precursor cells (MPCs), and serves as an indispensable adaptor for Pax7 to recruit the histone 3 lysine 4 (H3K4) methyltransferase (HMT) complex by bridging Pax7 and Wdr5. Knockdown of Pax3/7BP abolished the Pax3/7-associated H3K4 HMT activity and inhibited the proliferation of Pax7+ MPCs from young mice both in culture and in vivo. Id3 and Cdc20 were direct target genes of Pax7 and Pax3/7BP involved in the proliferation of Pax7+ MPCs. Collectively, our work establishes Pax3/7BP as an essential adaptor linking Pax3/7 with the H3K4 HMT to regulate the proliferation of MPCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Epigenesis, Genetic*
  • Histones / metabolism
  • Lysine / metabolism
  • Methyltransferases / metabolism
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • PAX3 Transcription Factor
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism*
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*

Substances

  • Histones
  • PAX3 Transcription Factor
  • PAX7 Transcription Factor
  • Paired Box Transcription Factors
  • Pax7 protein, mouse
  • Pax3 protein, mouse
  • Methyltransferases
  • Lysine