Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases
Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases
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DOI：
10.1007/978-3-031-11454-0_3
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发表时间：
2022-01-01
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影响因子：
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通讯作者：
Song, Jikui
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文献类型：
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作者：
Tajima, Shoji;Suetake, Isao;Song, Jikui
在哺乳动物中，已经鉴定了三种主要的DNA甲基转移酶，Dnmt 1、Dnmt 3a和Dnmt 3b。Dnmt 3a和Dnmt 3b负责在植入期胚胎和生殖细胞分化期间通过其新生型DNA甲基化活性建立DNA甲基化模式。Dnmt 3-like（Dnmt 31）是Dnmt 3家族的一员，但不具有DNA甲基化活性，是生殖细胞整体甲基化过程中不可或缺的一环。一旦DNA甲基化模式建立，维持型DNA甲基转移酶Dnmt 1通过复制忠实地将它们传播到下一代。所有Dnmts都具有多个域。例如，Dnmt 3a和Dnmt 3b各自含有识别组蛋白H3 K36 me 2/3标记的Pro-Trp-Trp-Pro（PWWP）结构域、识别未修饰的组蛋白H3尾的Atrx-Dnmt 3-Dnmt 31（ADD）结构域和甲基化CpG位点的催化结构域。Dnmt 1含有一个与多种调节因子相互作用的N端独立折叠结构域（NTD）、一个识别组蛋白H3 K9 me 3标记和H3泛素化的复制焦点靶向序列（RFTS）结构域、一个识别未修饰的CpG DNA的CXXC结构域、两个串联的溴邻同源结构域、一个识别未修饰的CpG DNA的CXXC结构域、一个识别未修饰的CpG DNA的CXXC结构域和一个识别未修饰的CpG DNA的CXXC结构域。（BAH 1和BAH 2）用BAH 1读取H4 K20 me 3标记的结构域，和优先甲基化半甲基化CpG位点的催化结构域。在本章中，这些结构域的结构和功能进行了描述。
In mammals, three major DNA methyltransferases, Dnmt1, Dnmt3a, and Dnmt3b, have been identified. Dnmt3a and Dnmt3b are responsible for establishing DNA methylation patterns produced through their de novo-type DNA methylation activity in implantation stage embryos and during germ cell differentiation. Dnmt3-like (Dnmt31), which is a member of the Dnmt3 family but does not possess DNA methylation activity, was reported to be indispensable for global methylation in germ cells. Once the DNA methylation patterns are established, maintenance-type DNA methyltransferase Dnmt1 faithfully propagates them to the next generation via replication. All Dnmts possess multiple domains. For instance, Dnmt3a and Dnmt3b each contain a Pro-Trp-Trp-Pro (PWWP) domain that recognizes the histone H3K36me2/3 mark, an Atrx-Dnmt3-Dnmt31 (ADD) domain that recognizes unmodified histone H3 tail, and a catalytic domain that methylates CpG sites. Dnmt1 contains an N-terminal independently folded domain (NTD) that interacts with a variety of regulatory factors, a replication foci-targeting sequence (RFTS) domain that recognizes the histone H3K9me3 mark and H3 ubiquitylation, a CXXC domain that recognizes unmodified CpG DNA, two tandem Bromo-Adjacent-homology (BAH1 and BAH2) domains that read the H4K20me3 mark with BAH1, and a catalytic domain that preferentially methylates hemimethylated CpG sites. In this chapter, the structures and functions of these domains are described.