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.
Keywords: DUX4; Facioscapulohumeral muscular dystrophy; Homo-dimerization; Nuclear localization; Protein cleavage; SMCHD1.