Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain
Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain
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DOI：
10.1016/s0960-9822(02)00901-6
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发表时间：
2002-06-25
期刊：
影响因子：
9.2
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Feng, Q;Wang, HB;Zhang, Y
核心组蛋白的N末端经过多种共价修饰，包括乙酰化、甲基化和磷酸化[1]。与乙酰化类似，组蛋白甲基化已成为调节染色质动力学和基因活性的重要因素[2-4]。组蛋白甲基化发生在精氨酸和赖氨酸残基上，由两个蛋白质家族催化，即蛋白精氨酸甲基转移酶家族和含有SET结构域的甲基转移酶家族[3]。在这里，我们报告了位于球状结构域的H3的赖氨酸79(K79)可以甲基化。K79甲基化存在于从酵母到人类的各种生物体中。在萌芽酵母中，K79甲基化是由沉默蛋白DOT1介导的。与K79甲基化的保守一致，DOT1同源物可以在各种真核生物中找到。我们鉴定了一个人DOT1样蛋白(DOT1L)，并在体外和体内证明该蛋白具有H3-K79特异性的组蛋白甲基转移酶(HMTase)活性。此外，我们发现K79甲基化水平在整个细胞周期中都受到调控。因此，我们的研究揭示了一个新的甲基化位点，并定义了一个新的组蛋白赖氨酸甲基转移酶家族。
The N-terminal tails of core histones are subjected to multiple covalent modifications, including acetylation, methylation, and phosphorylation [1]. Similar to acetylation, histone methylation has emerged as an important player in regulating chromatin dynamics and gene activity [2-4]. Histone methylation occurs on arginine and lysine residues and is catalyzed by two families of proteins, the protein arginine methyltransferase family and the SET-domain-containing methyltransferase family [3]. Here, we report that lysine 79 (K79) of H3, located in the globular domain, can be methylated. K79 methylation occurs in a variety of organisms ranging from yeast to human. In budding yeast, K79 methylation is mediated by the silencing protein DOT1. Consistent with conservation of K79 methylation, DOT1 homologs can be found in a variety of eukaryotic organisms. We identified a human DOT1-like (DOT1L) protein and demonstrated that this protein possesses intrinsic H3-K79-specific histone methyltransferase (HMTase) activity in vitro and in vivo. Furthermore, we found that K79 methylation level is regulated through out the cell cycle. Thus, our studies reveal a new methylation site and define a novel family of histone lysine methyltransferase.