组蛋白 H3 赖氨酸 56 甲基化通过与 PCNA 的相互作用调节 DNA 复制。
Histone H3 lysine 56 methylation regulates DNA replication through its interaction with PCNA.
机构信息
Molecular Biology Institute and Department of Biological Chemistry, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
出版信息
Mol Cell. 2012 Apr 13;46(1):7-17. doi: 10.1016/j.molcel.2012.01.019. Epub 2012 Mar 1.
Histone modifications play important roles in regulating DNA-based biological processes. Of the modified sites, histone H3 lysine 56 (H3K56) is unique in that it lies within the globular core domain near the entry-exit sites of the nucleosomal DNA superhelix and its acetylation state in yeast is a marker for newly synthesized histones in transcription, DNA repair, and DNA replication. We now report the presence of H3K56 monomethylation (H3K56me1) in mammalian cells and find that the histone lysine methytransferase G9a/KMT1C is required for H3K56me1 both in vivo and in vitro. We also find that disruption of G9a or H3K56 impairs DNA replication. Furthermore, H3K56me1 associates with the replication processivity factor PCNA primarily in G1 phase of the cell cycle and, directly, in vitro. These results find H3K56me1 in mammals and indicate a role for H3K56me1 as a chromatin docking site for PCNA prior to its function in DNA replication.
组蛋白修饰在调节基于 DNA 的生物过程中起着重要作用。在修饰的位点中，组蛋白 H3 赖氨酸 56（H3K56）是独特的，因为它位于球状核心结构域内，靠近核小体 DNA 超螺旋的进入/退出位点，其在酵母中的乙酰化状态是转录、DNA 修复和 DNA 复制中新生组蛋白的标志物。我们现在报告在哺乳动物细胞中存在 H3K56 单甲基化（H3K56me1），并发现组蛋白赖氨酸甲基转移酶 G9a/KMT1C 在体内和体外都需要 H3K56me1。我们还发现 G9a 或 H3K56 的破坏会损害 DNA 复制。此外，H3K56me1 主要在细胞周期的 G1 期与复制过程因子 PCNA 相关联，并且可以直接在体外与 PCNA 相关联。这些结果在哺乳动物中发现了 H3K56me1，并表明 H3K56me1 作为 PCNA 在 DNA 复制中的功能之前的染色质停泊位点的作用。
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