Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, 10016, USA.
Genes Dev. 2012 Feb 15;26(4):325-37. doi: 10.1101/gad.177444.111.
Histone post-translational modifications impact many aspects of chromatin and nuclear function. Histone H4 Lys 20 methylation (H4K20me) has been implicated in regulating diverse processes ranging from the DNA damage response, mitotic condensation, and DNA replication to gene regulation. PR-Set7/Set8/KMT5a is the sole enzyme that catalyzes monomethylation of H4K20 (H4K20me1). It is required for maintenance of all levels of H4K20me, and, importantly, loss of PR-Set7 is catastrophic for the earliest stages of mouse embryonic development. These findings have placed PR-Set7, H4K20me, and proteins that recognize this modification as central nodes of many important pathways. In this review, we discuss the mechanisms required for regulation of PR-Set7 and H4K20me1 levels and attempt to unravel the many functions attributed to these proteins.
组蛋白翻译后修饰影响染色质和核功能的许多方面。组蛋白 H4 赖氨酸 20 位甲基化 (H4K20me) 被认为参与调节从 DNA 损伤反应、有丝分裂浓缩和 DNA 复制到基因调控的各种过程。PR-Set7/Set8/KMT5a 是唯一催化 H4K20 单甲基化 (H4K20me1) 的酶。它是维持所有 H4K20me 水平所必需的,而且,重要的是,PR-Set7 的缺失对小鼠胚胎发育的早期阶段是灾难性的。这些发现将 PR-Set7、H4K20me 和识别这种修饰的蛋白质作为许多重要途径的中心节点。在这篇综述中,我们讨论了调节 PR-Set7 和 H4K20me1 水平所需的机制,并试图阐明这些蛋白质的许多功能。