Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 8, Pages 2713-2718Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0509503103
Keywords
skeletal muscle; sarcomere; myofiber maturation; cardiac muscle; transgenic fish
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Funding
- NIGMS NIH HHS [R01 GM058537, R01GM58537] Funding Source: Medline
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Histone modification has emerged as a fundamental mechanism for control of gene expression and cell differentiation. Recent studies suggest that SmyD1, a novo SET domain-containing protein, may play a critical role in cardiac muscle differentiation. However, its role in skeletal muscle development and its mechanism of actions remains elusive. Here we report that SmyD1a and SmyD1b, generated by alternative splicing of SmyD1 gene, are histone methyltransferases that play a key role in skeletal and cardiac muscle contraction. SmyDla and SmyD1b are specifically expressed in skeletal and cardiac muscles of zebrafish embryos. Knockdown of SmyDla and SmyD1b expression by morpholino antisense oligos resulted in malfunction of skeletal and cardiac muscles. The SmyD1 morphant embryos (embryos injected with morpholino oligos) could not swim and had no heartbeat. Myofibrii organization in the morphant embryos was severely disrupted. The affected myofibers appeared as immature fibers with centrally located nuclei. Together, these data indicate that SmyD1a and SmyD1b are histone methyltransferases and play a critical role in myofibril organization during myofiber maturation.
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