The DNA methyltransferases of mammals
The DNA methyltransferases of mammals
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DOI：
10.1093/hmg/9.16.2395
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发表时间：
2000-10-01
影响因子：
3.5
通讯作者：
Bestor, TH
中科院分区：
文献类型：
--
作者：
Bestor, TH
多年来，5-甲基胞嘧啶的生物学意义一直受到怀疑，但通过对小鼠的定向突变，人们已经了解到，生化测试表明参与建立、维持或解释基因组甲基化模式的每一种蛋白质都由一个必要的基因编码。最近发现一种人类遗传性疾病(ICF综合征)是由DNA甲基转移酶3B(Dnmt3b)基因突变引起的，另一种人类疾病(Rett综合征)被发现是由MECP2基因突变引起的，MECP2基因编码一种与甲基化DNA结合的蛋白质。由脱氧核糖核酸甲基转移酶-L(DNMT1)基因靶向突变引起的全球基因组去甲基化研究表明，胞嘧啶甲基化在X失活、基因组印迹和基因组中起重要作用。稳定状态。目前已知基因组中的大多数5-甲基胞嘧啶可以使哺乳动物基因组中积累的转座子和逆转录病毒的巨大负担在转录上保持沉默。甲基化模式的程序性变化在哺乳动物发育调控中的重要性也变得不像之前认为的那样重要。尽管一些悬而未决的问题尚未得到回答(其中一个问题涉及在配子发生和早期发育的特定阶段指定甲基化位置的线索的性质)，但对DNA甲基转移酶的研究可能会为进一步了解基因组甲基化模式的生物学功能提供进一步的见解。
The biological significance of 5-methylcytosine was in doubt for many years, but is no longer, Through targeted mutagenesis in mice it has been learnt that every protein shown by biochemical tests to be involved in the establishment, maintenance or interpretation of genomic methylation patterns is encoded by an essential gene. A human genetic disorder (ICF syndrome) has recently been shown to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene, A second human disorder (Rett syndrome) has been found to result from mutations in the MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome demethylation caused by targeted mutations in the DNA methyltransferase-l (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome. stabilization. The majority of genomic 5-methylcytosine is now known to enforce the transcriptional silence of the enormous burden of transposons and retroviruses that have accumulated in the mammalian genome. It has also become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed. Although a number of outstanding questions have yet to be answered (one of these questions involves the nature of the cues that designate sites for methylation at particular stages of gametogenesis and early development), studies of DNA methyltransferases are likely to provide further insights into the biological functions of genomic methylation patterns.