Madhani Hiten D
Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA; email:
Annu Rev Biophys. 2025 May;54(1):59-79. doi: 10.1146/annurev-biophys-070524-091904. Epub 2024 Dec 23.
In this article I review mechanisms that underpin epigenetic inheritance of CpG methylation and histone H3 lysine 9 methylation (H3K9me) in chromatin in fungi and mammals. CpG methylation can be faithfully inherited epigenetically at some sites for a lifetime in vertebrates and, remarkably, can be propagated for millions of years in some fungal lineages. Transmission of methylation patterns requires maintenance-type DNA methyltransferases (DNMTs) that recognize hemimethylated CpG DNA produced by replication. DNMT1 is the maintenance enzyme in vertebrates; we recently identified DNMT5 as an ATP-dependent CpG maintenance enzyme found in fungi and protists. In vivo, CpG methylation is coupled to H3K9me. H3K9me is itself reestablished after replication via local histone H3-H4 tetramer recycling involving mobile and nonmobile chaperones, de novo nucleosome assembly, and read-write mechanisms that modify naive nucleosomes. Additional proteins recognize hemimethylated CpG or fully methylated CpG-containing motifs and enhance restoration of methylation by recruiting and/or activating the maintenance methylase.
在本文中，我将综述真菌和哺乳动物染色质中支撑CpG甲基化和组蛋白H3赖氨酸9甲基化（H3K9me）表观遗传遗传的机制。在脊椎动物中，CpG甲基化能够在某些位点以表观遗传的方式忠实地遗传一生，并且值得注意的是，在某些真菌谱系中，它可以传播数百万年。甲基化模式的传递需要维持型DNA甲基转移酶（DNMT），该酶可识别复制产生的半甲基化CpG DNA。DNMT1是脊椎动物中的维持酶；我们最近将DNMT5鉴定为在真菌和原生生物中发现的一种依赖ATP的CpG维持酶。在体内，CpG甲基化与H3K9me相关联。H3K9me本身在复制后通过涉及移动和非移动伴侣蛋白的局部组蛋白H3-H4四聚体循环、从头核小体组装以及修饰未成熟核小体的读写机制得以重新建立。其他蛋白质可识别半甲基化的CpG或含有完全甲基化CpG的基序，并通过招募和/或激活维持甲基化酶来增强甲基化的恢复。
