Active DNA demethylation in plants and animals.
Active DNA demethylation in plants and animals.
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DOI：
10.1101/sqb.2012.77.014936
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Zhu JK
中科院分区：
文献类型：
--
作者：
Zhang H;Zhu JK
主动DNA去甲基化调节许多重要的生物学过程，包括植物和动物的早期发育和基因座特异性基因表达。在拟南芥中，双功能DNA糖基化酶直接切除5-甲基胞嘧啶碱基，然后在脱碱基位点切割DNA骨架。最近的证据表明，哺乳动物在5-甲基胞嘧啶被氧化和/或脱氨基后利用DNA糖基化酶。在这两种情况下，所产生的单核苷酸缺口随后通过DNA碱基切除修复途径用未修饰的胞嘧啶填充。5-甲基胞嘧啶的酶促去除与组蛋白修饰和可能的非编码RNA紧密结合。未来的研究将增加我们对各种细胞过程中活性DNA去甲基化的机制和关键作用的理解，并激发针对表观遗传疾病的新型遗传和化学疗法。
Active DNA demethylation regulates many vital biological processes, including early development and locus-specific gene expression in plants and animals. In Arabidopsis, bifunctional DNA glycosylases directly excise the 5-methylcytosine base and then cleave the DNA backbone at the abasic site. Recent evidence suggests that mammals utilize DNA glycosylases after 5-methylcytosine is oxidized and/or deaminated. In both cases, the resultant single-nucleotide gap is subsequently filled with an unmodified cytosine through the DNA base excision repair pathway. The enzymatic removal of 5-methylcytosine is tightly integrated with histone modifications and possibly noncoding RNAs. Future research will increase our understanding of the mechanisms and critical roles of active DNA demethylation in various cellular processes as well as inspire novel genetic and chemical therapies for epigenetic disorders.