Zhu Qifan, Stöger Reinhard, Alberio Ramiro
School of Biosciences, University of Nottingham, Nottingham, United Kingdom.
Front Cell Dev Biol. 2018 Mar 27;6:24. doi: 10.3389/fcell.2018.00024. eCollection 2018.
5-methylcytosine (5mC) on CpG dinucleotides has been viewed as the major epigenetic modification in eukaryotes for a long time. Apart from 5mC, additional DNA modifications have been discovered in eukaryotic genomes. Many of these modifications are thought to be solely associated with DNA damage. However, growing evidence indicates that some base modifications, namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), 5-carboxylcytosine (5caC), and N6-methadenine (6mA), may be of biological relevance, particularly during early stages of embryo development. Although abundance of these DNA modifications in eukaryotic genomes can be low, there are suggestions that they cooperate with other epigenetic markers to affect DNA-protein interactions, gene expression, defense of genome stability and epigenetic inheritance. Little is still known about their distribution in different tissues and their functions during key stages of the animal lifecycle. This review discusses current knowledge and future perspectives of these novel DNA modifications in the mammalian genome with a focus on their dynamic distribution during early embryonic development and their potential function in epigenetic inheritance through the germ line.
长期以来，CpG二核苷酸上的5-甲基胞嘧啶（5mC）一直被视为真核生物中的主要表观遗传修饰。除了5mC之外，在真核生物基因组中还发现了其他DNA修饰。其中许多修饰被认为仅与DNA损伤有关。然而，越来越多的证据表明，一些碱基修饰，即5-羟甲基胞嘧啶（5hmC）、5-甲酰基胞嘧啶（5fC）、5-羧基胞嘧啶（5caC）和N6-甲基腺嘌呤（6mA），可能具有生物学相关性，尤其是在胚胎发育的早期阶段。尽管这些DNA修饰在真核生物基因组中的丰度可能很低，但有迹象表明它们与其他表观遗传标记协同作用，以影响DNA-蛋白质相互作用、基因表达、基因组稳定性防御和表观遗传遗传。关于它们在不同组织中的分布以及在动物生命周期关键阶段的功能，我们仍然知之甚少。本综述讨论了哺乳动物基因组中这些新型DNA修饰的当前知识和未来前景，重点关注它们在早期胚胎发育过程中的动态分布以及它们通过种系在表观遗传遗传中的潜在功能。
