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J Mol Cell Biol. 2013 Oct;5(5):294-307. doi: 10.1093/jmcb/mjt018. Epub 2013 May 29.

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

Author information

  • 1Dulbecco Telethon Institute and Division of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milano, Italy.

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.

KEYWORDS:

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

PMID:
23720823
[PubMed - indexed for MEDLINE]
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