Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states
Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states
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DOI：
10.1038/nsmb.1432
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发表时间：
2008-06-01
影响因子：
16.8
通讯作者：
van Leeuwen, Fred
中科院分区：
文献类型：
--
作者：
Frederiks, Floor;Tzouros, Manuel;van Leeuwen, Fred
尽管组蛋白上赖氨酸的单甲基化、双甲基化和三甲基化状态通常具有特定功能，但迄今为止，尚未将特定功能归因于Dot 1产生的组蛋白H3赖氨酸79（H3 K79）的不同甲基化状态。在这里，我们表明，Dot1，与其他已知的组蛋白甲基转移酶，通过非进行性机制引入多个甲基。动力学机制意味着H3K79甲基化状态不能独立产生，表明功能冗余。事实上，酵母中依赖于Dot1的基因沉默依赖于全局H3K79甲基化水平，而不是一种特定的甲基化状态。此外，我们的研究结果表明，组蛋白H2B泛素化通过增强所有H3K79甲基化状态的合成来影响H3K79三甲基化。我们的研究结果表明，H3K79的多重甲基化导致了一个二进制代码，预计这将限制通过假定的脱甲基酶或结合蛋白进行调节的可能性。
Whereas mono-, di- and trimethylation states of lysines on histones typically have specific functions, no specific functions have been attributed so far to the different methylation states of histone H3 Lysine 79 (H3K79) generated by Dot1. Here we show that Dot1, in contrast to other known histone methyltransferases, introduces multiple methyl groups via a nonprocessive mechanism. The kinetic mechanism implies that the H3K79 methylation states cannot be generated independently, suggesting functional redundancy. Indeed, gene silencing in yeast, which is dependent on Dot1, relied on global H3K79 methylation levels and not on one specific methylation state. Furthermore, our findings suggest that histone H2B ubiquitination affects H3K79 trimethylation by enhancing synthesis of all H3K79 methylation states. Our results suggest that multiple methylation of H3K79 leads to a binary code, which is expected to limit the possibilities for regulation by putative demethylases or binding proteins.