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.

中文翻译：

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G9a/GLP 对 DNA 连接酶 1 的甲基化招募 UHRF1 复制 DNA 并调节 DNA 甲基化。

DNA 甲基化是哺乳动物中必不可少的表观遗传标记，必须在每一轮 DNA 复制后重新建立。蛋白质 UHRF1 对这个过程至关重要。有人提出该蛋白质通过协同结合半甲基化 DNA 和 H3K9me2/3 来靶向新复制的 DNA，但该模型留下了许多未解决的问题。在这里，我们提供了复制机制通过 DNA 连接酶 1 (LIG1) 直接招募 UHRF1 的证据。LIG1 中的组蛋白 H3K9 样模拟物被 G9a 和 GLP 甲基化，与 H3K9me2/3 相比，它更强烈地结合 UHRF1。与甲基化 LIG1 的相互作用促进 UHRF1 向 DNA 复制位点的募集，是 DNA 甲基化维持所必需的。这些结果进一步阐明了 UHRF1 的功能，确定了 G9a 和 GLP 的非组蛋白靶标，