Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association
Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association
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DOI：
10.1101/gad.1001502
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发表时间：
2002-06-15
影响因子：
10.5
通讯作者：
Struhl, K
中科院分区：
文献类型：
--
作者：
Ng, HH;Feng, Q;Struhl, K
氨基末端的组蛋白尾部经历共价翻译后修饰，例如乙酰化、甲基化和磷酸化。在组蛋白密码假说中，这些暴露的和非结构化的组蛋白尾部可接近一系列特异性识别各种修饰的组蛋白的调节因子，从而产生介导特定生物反应的改变的染色质结构。在这里，我们报告组蛋白H3的赖氨酸（Lys）79，它位于球状结构域，在真核生物中被甲基化。在酿酒酵母中，组蛋白H3的Lys 79被Dot 1甲基化，Dot 1是一种先前显示在端粒沉默中起作用的蛋白质。组蛋白H3的Lys 79的突变和破坏Dot 1的催化活性的突变损害端粒沉默，表明Dot 1主要通过Lys 79的甲基化介导端粒沉默。端粒沉默中的这种缺陷可能反映了Sir蛋白与LyS 79之间的所有相互作用，因为dot 1和LyS 79突变削弱了体内Sir 2和Sir 3与端粒区域的相互作用。我们的研究结果表明，核心球状域的组蛋白修饰具有重要的生物学功能。
The amino-terminal histone tails are subject to covalent post-translational modifications such as acetylation, methylation, and phosphorylation. In the histone code hypothesis, these exposed and unstructured histone tails are accessible to a repertoire of regulatory factors that specifically recognize the various modified histones, thereby generating altered chromatin structures that mediate specific biological responses. Here, we report that lysine (Lys) 79 of histone H3, which resides in the globular domain, is methylated in eukaryotic organisms. In the yeast Saccharomyces cerevisiae, Lys 79 of histone H3 is methylated by Dot1, a protein shown previously to play a role in telomeric silencing. Mutations of Lys 79 of histone H3 and mutations that abolish the catalytic activity of Dot1 impair telomeric silencing, suggesting that Dot1 mediates telomeric silencing largely through methylation of Lys 79. This defect in telomeric silencing might reflect ail interaction between Sir proteins and Lys 79, because dot1 and Lys 79 mutations weaken the interaction of Sir2 and Sir3 with the telomeric region in vivo. Our results indicate that histone modifications in the core globular domain have important biological functions.