p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci

Cristiano Simone, Sonia Vanina Forcales, David A. Hill, Anthony N. Imbalzano, Lucia Latella, Pier Lorenzo Puri

Research output: Contribution to journalArticlepeer-review

Abstract

During skeletal myogenesis, genomic reprogramming toward terminal differentiation is achieved by recruiting chromatin-modifying enzymes to muscle-specific loci. The relative contribution of extracellular signaling cascades in targeting these enzymes to individual genes is unknown. Here we show that the differentiation-activated p38 pathway targets the SWI-SNF chromatin-remodeling complex to myogenic loci. Upon differentiation, p38 kinases were recruited to the chromatin of muscle-regulatory elements. Blockade of p38α/β repressed the transcription of muscle genes by preventing recruitment of the SWI-SNF complex at these elements without affecting chromatin binding of muscle-regulatory factors and acetyltransferases. The SWI-SNF subunit BAF60 could be phosphorylated by p38α-β in vitro, and forced activation of p38α/β in myoblasts by expression of a constitutively active MKK6 (refs. 5-7) promoted unscheduled SWI-SNF recruitment to the myogenin promoter. Conversely, inactivation of SWI-SNF enzymatic subunits abrogated MKK6-dependent induction of muscle gene expression. These results identify an unexpected function of differentiation-activated p38 in converting external cues into chromatin modifications at discrete loci, by selectively targeting SWI-SNF to muscle-regulatory elements.

Original languageEnglish
Pages (from-to)738-743
Number of pages6
JournalNature Genetics
Volume36
Issue number7
DOIs
Publication statusPublished - Jul 2004

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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