Kim J K, Samaranayake M, Pradhan S
New England BioLabs, Ipswich, MA 01938, USA.
Cell Mol Life Sci. 2009 Feb;66(4):596-612. doi: 10.1007/s00018-008-8432-4.
DNA and histone methylation are linked and subjected to mitotic inheritance in mammals. Yet how methylation is propagated and maintained between successive cell divisions is not fully understood. A series of enzyme families that can add methylation marks to cytosine nucleobases, and lysine and arginine amino acid residues has been discovered. Apart from methyltransferases, there are also histone modification enzymes and accessory proteins, which can facilitate and/or target epigenetic marks. Several lysine and arginine demethylases have been discovered recently, and the presence of an active DNA demethylase is speculated in mammalian cells. A mammalian methyl DNA binding protein MBD2 and de novo DNA methyltransferase DNMT3A and DNMT3B are shown experimentally to possess DNA demethylase activity. Thus, complex mammalian epigenetic mechanisms appear to be dynamic yet reversible along with a well-choreographed set of events that take place during mammalian development.
在哺乳动物中，DNA甲基化和组蛋白甲基化相互关联并经历有丝分裂遗传。然而，甲基化在连续细胞分裂之间如何传播和维持尚未完全明了。一系列能够向胞嘧啶核碱基以及赖氨酸和精氨酸氨基酸残基添加甲基化标记的酶家族已被发现。除甲基转移酶外，还有组蛋白修饰酶和辅助蛋白，它们可促进和/或靶向表观遗传标记。最近发现了几种赖氨酸和精氨酸去甲基化酶，并且推测在哺乳动物细胞中存在活性DNA去甲基化酶。实验表明，哺乳动物甲基DNA结合蛋白MBD2以及从头DNA甲基转移酶DNMT3A和DNMT3B具有DNA去甲基化酶活性。因此，复杂的哺乳动物表观遗传机制似乎是动态的，但又是可逆的，同时伴随着哺乳动物发育过程中精心编排的一系列事件。
