DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development
DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development
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DOI：
10.1016/s0092-8674(00)81656-6
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发表时间：
1999-10-29
期刊：
影响因子：
64.5
通讯作者：
Li, E
中科院分区：
文献类型：
--
作者：
Okano, M;Bell, DW;Li, E
DNA甲基化模式的建立需要从头开始的甲基化，这种甲基化主要发生在小鼠的早期发育和配子发生期间。在这里，我们证明了最近发现的两个DNA甲基转移酶，DNMT3A和DNMT3B，对于从头甲基化和小鼠发育是必不可少的。通过基因靶向失活这两个基因可以阻止ES细胞和早期胚胎中的从头甲基化，但对印迹甲基化模式的维持没有影响。DNMT3a和Dnmt3b在发育过程中也表现出不重叠的功能，Dnmt3b是着丝粒微小卫星重复序列甲基化所特需的。在ICF综合征中发现了人类Dnmt3b的突变，这是一种以着丝粒周围重复序列低甲基化为特征的发育缺陷。我们的结果表明，DNMT3A和DNMT3B都是从头开始的甲基转移酶，在正常发育和疾病中发挥重要作用。
The establishment of DNA methylation patterns requires de novo methylation that occurs predominantly during early development and gametogenesis in mice. Here we demonstrate that two recently identified DNA methyltransferases, Dnmt3a and Dnmt3b, are essential for de novo methylation and for mouse development. inactivation of both genes by gene targeting blocks de novo methylation in ES cells and early embryos, but it has no effect on maintenance of imprinted methylation patterns. Dnmt3a and Dnmt3b also exhibit nonoverlapping functions in development, with Dnmt3b specifically required for methylation of centromeric minor satellite repeats. Mutations of human DNMT3B are found in ICF syndrome, a developmental defect characterized by hypomethylation of pericentromeric repeats. Our results indicate that both Dnmt3a and Dnmt3b function as de novo methyltransferases that play important roles in normal development and disease.