title: Defective myogenesis in the absence of the muscle-specific lysine methyltransferase SMYD1.
abstract: The SMYD (SET and MYND domain) family of lysine methyltransferases harbor a unique structure in which the methyltransferase (SET) domain is intervened by a zinc finger protein-protein interaction MYND domain. SMYD proteins methylate both histone and non-histone substrates and participate in diverse biological processes including transcriptional regulation, DNA repair, proliferation and apoptosis. Smyd1 is unique among the five family members in that it is specifically expressed in striated muscles. Smyd1 is critical for development of the right ventricle in mice. In zebrafish, Smyd1 is necessary for sarcomerogenesis in fast-twitch muscles. Smyd1 is expressed in the skeletal muscle lineage throughout myogenesis and in mature myofibers, shuttling from nucleus to cytosol during myoblast differentiation. Because of this expression pattern, we hypothesized that Smyd1 plays multiple roles at different stages of myogenesis. To determine the role of Smyd1 in mammalian myogenesis, we conditionally eliminated Smyd1 from the skeletal muscle lineage at the myoblast stage using Myf5(cre). Deletion of Smyd1 impaired myoblast differentiation, resulted in fewer myofibers and decreased expression of muscle-specific genes. Muscular defects were temporally restricted to the second wave of myogenesis. Thus, in addition to the previously described functions for Smyd1 in heart development and skeletal muscle sarcomerogenesis, these results point to a novel role for Smyd1 in myoblast differentiation.
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Harika
authors.initials: H
authors.lastname: Nagandla
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Suhujey
authors.initials: S
authors.lastname: Lopez
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA; Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Rasmussen
authors.affiliation: Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, USA.
authors.forename: Haley O
authors.initials: HO
authors.lastname: Tucker
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA; Stem Cell Engineering Department, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA. Electronic address: dstewart@uh.edu.
authors.forename: M David
authors.initials: MD
authors.lastname: Stewart
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal; D009124:Muscle Proteins / Q000032:analysis / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C096485:Smyd1 protein, mouse; D014157:Transcription Factors
keywords: Development; Methylation; Muscle; Myogenesis; SMYD1