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

ABSTRACT: 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.

SUBMITTER: Hiramuki Y

PROVIDER: S-EPMC6090946 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Hiramuki Yosuke Y Tapscott Stephen J SJ

Skeletal muscle 20180802 1

<h4>Background</h4>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.<h4>Methods</h4>We made and analyzed lenti-viral vectors that express Flag-tagged full-length or different mutant SMCHD1 proteins to better understand the functional domains ...[more]

PMID: 30071896

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