Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
J Biol Chem. 2011 May 27;286(21):18347-53. doi: 10.1074/jbc.R110.205286. Epub 2011 Mar 24.
Cell type-specific DNA methylation patterns are established during mammalian development and maintained in adult somatic cells. Understanding how these patterns of 5-methylcytosine are established and maintained requires the elucidation of mechanisms for both DNA methylation and demethylation. The enzymes involved in the de novo methylation of DNA and the maintenance of the resulting methylation patterns have been fairly well characterized. However, important remaining challenges are to understand how DNA methylation systems function in vivo and in the context of chromatin. In addition, the enzymes and mechanisms for demethylation remain to be elucidated. There is still no consensus as to how active enzymatic demethylation is achieved in mammalian cells, but recent studies implicate base excision repair for genome-wide DNA demethylation in germ cells and early embryos.
哺乳动物发育过程中建立了细胞类型特异性的 DNA 甲基化模式，并在成年体细胞中维持这些模式。了解这些 5-甲基胞嘧啶模式是如何建立和维持的，需要阐明 DNA 甲基化和去甲基化的机制。涉及 DNA 从头甲基化和维持甲基化模式的酶已得到相当充分的描述。然而，仍然存在重要的挑战，需要了解 DNA 甲基化系统在体内和染色质背景下的功能。此外，去甲基化的酶和机制仍有待阐明。目前对于如何在哺乳动物细胞中实现有效的酶促去甲基化还没有共识，但最近的研究表明，在生殖细胞和早期胚胎中，碱基切除修复可实现全基因组 DNA 去甲基化。
