Lysine Methyltransferase SMYD1 Regulates Myogenesis via skNAC Methylation

Li Zhu; Mark A. Brown; Robert J. Sims; Gayatri R. Tiwari; Hui Nie; R. Dayne Mayfield; Haley O. Tucker

doi:10.3390/cells12131695

Cells (Jun 2023)

Lysine Methyltransferase SMYD1 Regulates Myogenesis via skNAC Methylation

Li Zhu,
Mark A. Brown,
Robert J. Sims,
Gayatri R. Tiwari,
Hui Nie,
R. Dayne Mayfield,
Haley O. Tucker

Affiliations

Li Zhu: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5000, Austin, TX 78712, USA
Mark A. Brown: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5000, Austin, TX 78712, USA
Robert J. Sims: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5000, Austin, TX 78712, USA
Gayatri R. Tiwari: Center for Biomedical Research Services, Department of Neuroscience, The University of Texas at Austin, 2500 Speedway A4800, Austin, TX 78712, USA
Hui Nie: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5000, Austin, TX 78712, USA
R. Dayne Mayfield: Center for Biomedical Research Services, Department of Neuroscience, The University of Texas at Austin, 2500 Speedway A4800, Austin, TX 78712, USA
Haley O. Tucker: Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5000, Austin, TX 78712, USA

DOI: https://doi.org/10.3390/cells12131695
Journal volume & issue: Vol. 12, no. 13
p. 1695

Abstract

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The SMYD family is a unique class of lysine methyltransferases (KMTases) whose catalytic SET domain is split by a MYND domain. Among these, Smyd1 was identified as a heart- and skeletal muscle-specific KMTase and is essential for cardiogenesis and skeletal muscle development. SMYD1 has been characterized as a histone methyltransferase (HMTase). Here we demonstrated that SMYD1 methylates Skeletal muscle-specific splice variant of the Nascent polypeptide-Associated Complex (skNAC) transcription factor. SMYD1-mediated methylation of skNAC targets K1975 within the carboxy-terminus region of skNAC. Catalysis requires physical interaction of SMYD1 and skNAC via the conserved MYND domain of SMYD1 and the PXLXP motif of skNAC. Our data indicated that skNAC methylation is required for the direct transcriptional activation of myoglobin (Mb), a heart- and skeletal muscle-specific hemoprotein that facilitates oxygen transport. Our study revealed skNAC as a methylation target of SMYD1, illuminates the molecular mechanism by which SMYD1 cooperates with skNAC to regulate transcriptional activation of genes crucial for muscle functions and implicates the MYND domain of the SMYD-family KMTases as an adaptor to target substrates for methylation.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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