Preferential dimethylation of histone H4 lysine 20 by Suv4-20
Preferential dimethylation of histone H4 lysine 20 by Suv4-20
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DOI：
10.1074/jbc.m707974200
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发表时间：
2008-05-02
影响因子：
4.8
通讯作者：
Mizzen, Craig A.
中科院分区：
文献类型：
--
作者：
Yang, Hongbo;Pesavento, James J.;Mizzen, Craig A.
组蛋白尾部的翻译后修饰指导核过程，包括转录、DNA修复和染色质包装。组蛋白H4的赖氨酸20在体内被单甲基化、二甲基化或三甲基化，但这些甲基化的调节和意义知之甚少。SET结构域蛋白PR-Set 7和Suv 4 -20分别与单甲基化和三甲基化有关;然而，还没有鉴定出使赖氨酸20二甲基化的酶。果蝇Suv 4 -20是一种混合产物特异性甲基转移酶，在S2细胞中，其赖氨酸20处的二甲基化作用约占总H4的90%，而三甲基化作用不到5%。三甲基化，但不二甲基化，减少在缺乏HP 1的果蝇幼虫，这表明与HP 1的相互作用调节Suv 4 -20的产品特异性和异染色质内的三甲基赖氨酸20的富集。与果蝇酶类似，人Suv 4 - 20 h1/h2酶产生二-和三甲基赖氨酸20。PR-Set 7和Suv 4 -20都是正常甲基化水平所必需的，这表明它们具有非冗余功能。Suv 4 - 20敲低或过表达后赖氨酸20甲基化水平的改变不影响赖氨酸16乙酰化，表明这两种修饰在体内不具有竞争性。Suv 4 -20 h1/h2在HeLa细胞中的消耗损害了53 BP 1灶的形成，表明二甲基赖氨酸20是适当的DNA损伤反应所必需的。总的来说，数据表明Suv 4 -20产生几乎无处不在的二甲基化，其促进DNA损伤反应和参与异染色质形成的选择性三甲基化。
Post-translational modifications of histone tails direct nuclear processes including transcription, DNA repair, and chromatin packaging. Lysine 20 of histone H4 is mono-, di-, or trimethylated in vivo, but the regulation and significance of these methylations is poorly understood. The SET domain proteins PR-Set7 and Suv4-20 have been implicated in mono- and trimethylation, respectively; however, enzymes that dimethylate lysine 20 have not been identified. Here were port that Drosophila Suv4-20 is a mixed product specificity methyltransferase that dimethylates similar to 90% and trimethylates less than 5% of total H4 at lysine 20 in S2 cells. Trimethylation, but not dimethylation, is reduced in Drosophila larvae lacking HP1, suggesting that an interaction with HP1 regulates the product specificity of Suv4-20 and enrichment of trimethyllysine 20 within heterochromatin. Similar to the Drosophila enzyme, human Suv4-20h1/h2 enzymes generate di- and trimethyllysine 20. PR-Set7 and Suv4-20 are both required for normal levels of methylation, suggesting they have non-redundant functions. Alterations in the level of lysine 20 methylation following knock-down or overexpression of Suv4- 20 did not affect lysine 16 acetylation, revealing that these two modifications are not competitive in vivo. Depletion of Suv4-20 h1/h2 in HeLa cells impaired the formation of 53BP1 foci, suggesting dimethyllysine 20 is required for a proper DNA damage response. Collectively, the data indicate that Suv4-20 generates nearly ubiquitous dimethylation that facilitates the DNA damage response and selective trimethylation that is involved in heterochromatin formation.