Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation
Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation
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DOI：
10.1016/j.molcel.2017.07.012
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发表时间：
2017-08-17
期刊：
影响因子：
16
通讯作者：
Defossez, Pierre-Antoine
中科院分区：
文献类型：
--
作者：
Ferry, Laure;Fournier, Alexandra;Defossez, Pierre-Antoine
DNA甲基化是哺乳动物中一种重要的表观遗传标记，在每一轮DNA复制后都必须重新建立。蛋白质UHRF 1是这个过程中必不可少的;有人提出，该蛋白质的目标是通过合作结合半甲基化的DNA和H3 K9 me 2/3的新复制的DNA，但这个模型留下了一些问题没有答案。在这里，我们提出的证据直接招聘UHRF 1的复制机器通过DNA连接酶1（LIG 1）。LIG 1中的组蛋白H3 K9样模拟物被G9 a和GLP甲基化，并且与H3 K9 me 2/3相比，更强烈地结合UHRF 1。与甲基化LIG 1的相互作用促进UHRF 1向DNA复制位点的募集，并且是DNA甲基化维持所必需的。这些结果进一步阐明了UHRF 1的功能，鉴定了G9 a和GLP的非组蛋白靶标，并提供了协调DNA复制和DNA甲基化维持的组蛋白模拟物的实例。
DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1. Interaction with methylated LIG1 promotes the recruitment of UHRF1 to DNA replication sites and is required for DNA methylation maintenance. These results further elucidate the function of UHRF1, identify a non-histone target of G9a and GLP, and provide an example of a histone mimic that coordinates DNA replication and DNA methylation maintenance.