Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Japan.
PLoS One. 2011;6(8):e23491. doi: 10.1371/journal.pone.0023491. Epub 2011 Aug 24.
Modifications of histone tails are involved in the regulation of a wide range of biological processes including cell cycle, cell survival, cell division, and cell differentiation. Among the modifications, histone methylation plays a critical role in cardiac and skeletal muscle differentiation. In our earlier studies, we found that SMYD3 has methyltransferase activity to histone H3 lysine 4, and that its up-regulation is involved in the tumorigenesis of human colon, liver, and breast. To clarify the role of Smyd3 in development, we have studied its expression patterns in zebrafish embryos and the effect of its suppression on development using Smyd3-specific antisense morpholino-oligonucleotides. We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle.
组蛋白尾部的修饰参与调节广泛的生物学过程，包括细胞周期、细胞存活、细胞分裂和细胞分化。在这些修饰中，组蛋白甲基化在心脏和骨骼肌肉分化中起着关键作用。在我们之前的研究中，我们发现 SMYD3 具有组蛋白 H3 赖氨酸 4 的甲基转移酶活性，其上调参与了人类结肠、肝脏和乳腺的肿瘤发生。为了阐明 Smyd3 在发育中的作用，我们研究了其在斑马鱼胚胎中的表达模式，并使用 Smyd3 特异性反义 morpholino-oligonucleotides 抑制其表达对发育的影响。我们在这里显示，smyd3 的转录本在所有检查的发育阶段的斑马鱼胚胎中表达，并且 smyd3 在胚胎中的敲低导致心包水肿和躯干结构缺陷。此外，这些表型与三个心腔标记物包括 cmlc2、amhc 和 vmhc 的异常表达以及包括 myod 和 myog 在内的肌生成调节因子的异常表达有关。这些数据表明 Smyd3 在心脏和骨骼肌肉发育中发挥重要作用。
