Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Epigenetics. 2011 Sep 1;6(9):1059-67. doi: 10.4161/epi.6.9.16069.
SET domain lysine methyltransferases (KMTs) catalyze the site- and state-specific methylation of lysine residues in histone and non-histone substrates. These modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation and DNA damage response, and have been implicated in the epigenetic regulation of cell identity and fate. The substrate and product specificities of SET domain KMTs are pivotal to eliciting these effects due to the distinct functions associated with site and state-specific protein lysine methylation. Here, we review advances in understanding the molecular basis of these specificities gained through structural and biochemical studies of the human methyltransferases Mixed Lineage Leukemia 1 (MLL1, also known as KMT2A) and SET7/9 (KMT7). We conclude by exploring the broader implications of these findings on the biological functions of protein lysine methylation by SET domain KMTs.
SET 结构域赖氨酸甲基转移酶（KMTs）催化组蛋白和非组蛋白底物中赖氨酸残基的位点和状态特异性甲基化。这些修饰在转录调控、异染色质形成、X 染色体失活和 DNA 损伤反应中发挥着基本作用，并被牵连到细胞身份和命运的表观遗传调控中。SET 结构域 KMTs 的底物和产物特异性对于产生这些效应至关重要，因为与位点和状态特异性蛋白赖氨酸甲基化相关的功能是不同的。在这里，我们通过对人类甲基转移酶混合谱系白血病 1（MLL1，也称为 KMT2A）和 SET7/9（KMT7）的结构和生化研究，综述了对这些特异性的分子基础的理解进展。最后，我们探讨了这些发现对 SET 结构域 KMTs 介导的蛋白质赖氨酸甲基化的生物学功能的更广泛影响。
