p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation

Nat Struct Mol Biol. 2007 Dec;14(12):1150-6. doi: 10.1038/nsmb1316. Epub 2007 Nov 18.


Cell-specific patterns of gene expression are established through the antagonistic functions of trithorax group (TrxG) and Polycomb group (PcG) proteins. Several muscle-specific genes have previously been shown to be epigenetically marked for repression by PcG proteins in muscle progenitor cells. Here we demonstrate that these developmentally regulated genes become epigenetically marked for gene expression (trimethylated on histone H3 Lys4, H3K4me3) during muscle differentiation through specific recruitment of Ash2L-containing methyltransferase complexes. Targeting of Ash2L to specific genes is mediated by the transcriptional regulator Mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 MAPK signaling pathway via phosphorylation of Mef2d. Thus, we provide evidence that signaling pathways regulate the targeting of TrxG-mediated epigenetic modifications at specific promoters during cellular differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / genetics*
  • Methyltransferases / metabolism*
  • Mice
  • Muscles / enzymology
  • Muscles / metabolism
  • Polycomb-Group Proteins
  • Promoter Regions, Genetic
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Chromosomal Proteins, Non-Histone
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Methyltransferases
  • p38 Mitogen-Activated Protein Kinases