Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature genetics, 2004-07, Vol.36 (7), p.738-743

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 5,6,7) 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.