A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns
A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns
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具有简并序列特异性的古细菌原型赖氨酸甲基转移酶 4 以不同模式甲基化染色质蛋白 Sul7d 和 Cren7
DOI：
10.1074/jbc.m113.452979
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发表时间：
2013-05-10
影响因子：
4.8
通讯作者：
Cao, Qinhong
中科院分区：
文献类型：
--
作者：
Niu, Yanling;Xia, Yisui;Cao, Qinhong
组蛋白甲基化是早期分化单细胞真核生物的主要表观遗传修饰之一。我们发现，一个广泛的赖氨酸甲基转移酶，从pneumea（aKMT4），具有惊人的结构和功能相似的核心远亲真核KMT4/Dot1。aKMT4甲基化一组不同的蛋白质，包括染色质蛋白Sul7d和Cren7，以及RNA外泌体组分。Cs14-和Rrp4-外泌体复合物以不同的模式甲基化。aKMT4可以在分子内自我甲基化，并与其他蛋白质竞争甲基。自甲基化被合适的底物或DNA以浓度依赖性方式抑制。自甲基化的酶显示出相对受损的活性。aKMT4 - 8A突变体的自甲基化作用被消除，底物甲基化增加了150%以上，提示可能存在调节甲基转移酶活性的机制。更有趣的是，Sul7d的甲基化，而不是Cren7，通过aKMT4被DNA显着增强。MS/MS和动力学分析进一步表明aKMT4在染色质环境中甲基化Sul7d。这些数据提供了一个线索，aKMT4活性的可能调控的局部染色质环境，虽然作为一个混杂的酶所需的广泛和多样化的赖氨酸甲基化硫化叶菌。本研究支持了真核生物组蛋白修饰酶的原核起源模型，并为古细菌染色质的调控提供了线索。
Histone methylation is one of the major epigenetic modifications even in early diverging unicellular eukaryotes. We show that a widespread lysine methyltransferase from Archaea (aKMT4), bears striking structural and functional resemblance to the core of distantly related eukaryotic KMT4/Dot1. aKMT4 methylates a set of various proteins, including the chromatin proteins Sul7d and Cren7, and RNA exosome components. Csl4- and Rrp4-exosome complexes are methylated in different patterns. aKMT4 can self-methylate intramolecularly and compete with other proteins for the methyl group. Automethylation is inhibited by suitable substrates or DNA in a concentration-dependent manner. The automethylated enzyme shows relatively compromised activity. aKMT4-8A mutant with abrogated automethylation shows a more than 150% increase in methylation of substrates, suggesting a possible mechanism to regulate methyltransferase activity. More interestingly, methylation of Sul7d, but not Cren7, by aKMT4 is significantly enhanced by DNA. MS/MS and kinetic analysis further suggest that aKMT4 methylates Sul7d in the chromatin context. These data provide a clue to the possible regulation of aKMT4 activity by the local chromatin environment, albeit as a promiscuous enzyme required for extensive and variegated lysine methylation in Sulfolobus. This study supports the prokaryotic origin model of eukaryotic histone modification enzymes and sheds light on regulation of archaeal chromatin.