SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos
SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos
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DOI：
10.1073/pnas.0509503103
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发表时间：
2006-02-21
影响因子：
11.1
通讯作者：
Du, SJ
中科院分区：
文献类型：
--
作者：
Tan, XG;Rotllant, J;Du, SJ
组蛋白修饰已成为控制基因表达和细胞分化的基本机制。最近的研究表明，SmyD1是一种包含novo set结构域的蛋白，可能在心肌分化过程中发挥关键作用。然而，它在骨骼肌发育中的作用及其作用机制仍然难以捉摸。SmyD1a和SmyD1b是组蛋白甲基转移酶，在骨骼肌和心肌收缩中起关键作用。SmyD1a和SmyD1b在斑马鱼胚胎的骨骼肌和心肌中特异表达。吗啡反义寡核苷酸下调SmyD1a和SmyD1b的表达可导致骨骼肌和心肌功能障碍。SmyD1变异胚胎(注射吗啉寡核苷酸的胚胎)不会游泳，也没有心跳。变异胚胎中的肌原纤维组织被严重破坏。受累的肌纤维表现为未成熟的肌纤维，细胞核居中。综上所述，这些数据表明SmyD1a和SmyD1b是组蛋白甲基转移酶，在肌纤维成熟过程中对肌原纤维的组织起关键作用。
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.