SET domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3
SET domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3
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DOI：
10.1074/jbc.m101914200
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发表时间：
2001-07-06
影响因子：
4.8
通讯作者：
Shinkai, Y
中科院分区：
文献类型：
--
作者：
Tachibana, M;Sugimoto, K;Shinkai, Y
组蛋白尾部的共价修饰在多种核过程中具有调节作用，如转录控制和有丝分裂染色体凝聚。在已知的催化共价修饰的不同类型的酶中，最新增加的是组蛋白甲基转移酶(HMTase)，其功能目前正在研究中。在这里，我们发现了一个含有SET结构域的蛋白G9a，它是一种新的哺乳动物赖氨酸偏好HMTase。与第一个发现的偏爱赖氨酸的哺乳动物HMTase Suv39 H1一样，G9a将甲基转移到组蛋白H3的赖氨酸残基上，但据报道，H3中的赖氨酸4、9和27在哺乳动物细胞中甲基化。与Suv39 hi相比，G9a能够在H3的9位和27位赖氨酸上增加甲基，而Suv39 hi只能甲基化9位赖氨酸。我们的数据清楚地表明G9a具有不同于Suv39 H1及其同系物H2的酶性质。最后，荧光蛋白标记的G9a定位于着丝粒基因的核内，而不是位于着丝粒基因的抑制性染色质区域，Suv39 H1家族蛋白定位于此。这一发现表明，G9a可能有助于非着丝粒基因座高阶染色质结构的组织。
The covalent modification of histone tails has regulatory roles in various nuclear processes, such as control of transcription and mitotic chromosome condensation. Among the different groups of enzymes known to catalyze the covalent modification, the most recent additions are the histone methyltransferases (HMTases), whose functions are now being characterized. Here we show that a SET domain-containing protein, G9a, is a novel mammalian lysine-preferring HMTase. Like Suv39 h1, the first identified lysine-preferring mammalian HMTase, G9a transfers methyl groups to the lysine residues of histone H3, but with a 10-20-fold higher activity, It was reported that lysines 4, 9, and 27 in H3 are methylated in mammalian cells. G9a was able to add methyl groups to lysine 27 as well as 9 in H3, compared with Suv39 hi, which was only able to methylate lysine 9, Our data clearly demonstrated that G9a has an enzymatic nature distinct from Suv39 h1 and its homologue h2, Finally, fluorescent protein-labeled G9a was shown to be localized in the nucleus but not in the repressive chromatin domains of centromeric loci, in which Suv39 h1 family proteins were localized. This finding indicates that G9a may contribute to the organization of the higher order chromatin structure of non-centromeric loci.