Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI, 48824, USA.
Department of Biochemistry & Molecular Biology, College of Nature Sciences, Michigan State University, East Lansing, MI, 48824, USA.
Biochem Biophys Res Commun. 2022 Apr 9;599:142-147. doi: 10.1016/j.bbrc.2022.02.043. Epub 2022 Feb 12.
Although post-translational modifications (-PTMs) of some histone H3 lysine residues are well studied, the PTMs of histone H3 lysine 37 in mammalian cells remain largely unknown. In this study, we provide evidence to show that SMYD family member 5 (SMYD5) is a histone H3-specfic methyltransferase that catalyzes mono-methylation of H3 lysine 36 and 37 (H3K36/K37me1) in vitro. The site-mutagenesis analysis shows that a species-conserved histidine in its catalytic SET domain is required for its histone methyltransferase activity. Genetic deletion of Smyd5 in murine embryonic stem cells (mESCs) partially reduces the global histone H3K37me1 level in cells, suggesting SMYD5 is one of histone methyltransferases catalyzing histone H3K37me1 in vivo. Hence, our study reveals that SMYD5 is a histone H3-specific methyltransferase that mediates histone H3K36/K37me1, which provides a biochemical basis for further studying its functions in mammalian cells.
尽管一些组蛋白 H3 赖氨酸残基的翻译后修饰（PTMs）已经得到了很好的研究，但哺乳动物细胞中组蛋白 H3 赖氨酸 37 的 PTM 仍然知之甚少。在这项研究中，我们提供了证据表明，SMYD 家族成员 5（SMYD5）是一种组蛋白 H3 特异性甲基转移酶，能够在体外催化 H3 赖氨酸 36 和 37 的单甲基化（H3K36/K37me1）。位点突变分析表明，其催化 SET 结构域中的一个物种保守的组氨酸对于其组蛋白甲基转移酶活性是必需的。Smyd5 在小鼠胚胎干细胞（mESCs）中的基因缺失部分降低了细胞中全局组蛋白 H3K37me1 水平，这表明 SMYD5 是催化组蛋白 H3K37me1 的组蛋白甲基转移酶之一。因此，我们的研究揭示了 SMYD5 是一种组蛋白 H3 特异性甲基转移酶，介导组蛋白 H3K36/K37me1，为进一步研究其在哺乳动物细胞中的功能提供了生化基础。
