Identification of SMCHD1 domains for nuclear localization, homo-dimerization, and protein cleavage
Yosuke Hiramuki1, Stephen J Tapscott2
1Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
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.
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