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DAVIDE CORONA

FSHD muscular dystrophy Region Gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis

  • Autori: Neguembor MV; Xynos A; Onorati MC; Caccia R; Bortolanza S; Godio C; Pistoni M; Corona D; Schotta G; Gabellini D
  • Anno di pubblicazione: 2013
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/75269

Abstract

Facioscapulohumeral Muscular Dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It is associated with deletion of a macrosatellite repeat leading to over-expression of the nearby genes. Among them, we focused on FSHD Region Gene 1 (FRG1) since its over-expression in mice, X. laevis and C. elegans leads to muscular dystrophy-like defects, suggesting that FRG1 plays a relevant role in muscle biology. Here we show that, when overexpressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. Moreover, Suv4-20h KO mice develop muscular dystrophy signs. Finally, we identify the FRG1/Suv4-20h1 target Eid3 as a novel myogenic inhibitor that contributes to the muscle differentiation defects. Our study suggests a novel role of FRG1 as epigenetic regulator of muscle differentiation and indicates that Suv4-20h1 has a gene-specific function in myogenesis.