Identification of SMCHD1 domains for nuclear localization, homo-dimerization, and protein cleavage

BACKGROUND: SMCHD1 is a disease modifier and a causative gene for facioscapulohumeral muscular dystrophy (FSHD) type 1 and type 2, respectively. A large variety of different mutations in SMCHD1 have been identified as causing FSHD2. In many cases, it is unclear how these mutations disrupt the normal function of SMCHD1. METHODS: We made and analyzed lenti-viral vectors that express Flag-tagged full-length or different mutant SMCHD1 proteins to better understand the functional domains of SMCHD1 in muscle cells. RESULTS: We identified regions necessary for nuclear localization, dimerization, and cleavage sites. Moreover, we confirmed that some mutants increased DUX4 expression in FSHD1 myoblasts. CONCLUSIONS: These findings provide an additional basis for understanding the molecular consequences of SMCHD1 mutations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13395-018-0172-z) contains supplementary material, which is available to authorized users.