Article abstract


Nature Structural & Molecular Biology 14, 1150 - 1156 (2007)
Published online: 18 November 2007 | doi:10.1038/nsmb1316

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

Shravanti Rampalli1, LiFang Li1, Esther Mak1, Kai Ge2, Marjorie Brand1,3, Stephen J Tapscott4 & F Jeffrey Dilworth1,3


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.

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  1. Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada.
  2. National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
  3. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8L6, Canada.
  4. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

Correspondence to: F Jeffrey Dilworth1,3 e-mail: jdilworth@ohri.ca



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