FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis

Maria Victoria Neguembor, Alexandros Xynos, Maria Cristina Onorati, Roberta Caccia, Sergia Bortolanza, Cristina Godio, Mariaelena Pistoni, Davide F. Corona, Gunnar Schotta, Davide Gabellini

Research output: Contribution to journalArticle

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, Xenopus laevis and Caenorhabditis elegans, leads to muscular dystrophy-like defects, suggesting that FRG1 plays a relevant role in muscle biology. Here we show that, when over-expressed, 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.

Original languageEnglish
Pages (from-to)294-307
Number of pages14
JournalJournal of Molecular Cell Biology
Volume5
Issue number5
DOIs
Publication statusPublished - Oct 2013

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Keywords

  • chromatin
  • copy number variation
  • D4Z4
  • H4K20
  • KMT5B
  • muscle differentiation
  • SUV4-20H1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics

Cite this

Neguembor, M. V., Xynos, A., Onorati, M. C., Caccia, R., Bortolanza, S., Godio, C., Pistoni, M., Corona, D. F., Schotta, G., & Gabellini, D. (2013). FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis. Journal of Molecular Cell Biology, 5(5), 294-307. https://doi.org/10.1093/jmcb/mjt018