The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly

J Cell Biol. 2011 Aug 22;194(4):551-65. doi: 10.1083/jcb.201010090.

Abstract

The molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Chromatin Assembly and Disassembly*
  • Fibroblasts / enzymology
  • Gene Expression Regulation
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism*
  • Humans
  • MEF2 Transcription Factors
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mice
  • Muscle Development* / genetics
  • Mutation
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myoblasts, Skeletal / enzymology*
  • Myofibrils / enzymology*
  • Myogenic Regulatory Factors / genetics
  • Myogenic Regulatory Factors / metabolism
  • RNA Interference
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Transfection
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Histones
  • MEF2 Transcription Factors
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myogenic Regulatory Factors
  • Repressor Proteins
  • Zebrafish Proteins
  • Suv39h1 protein, mouse
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase