哺乳动物DNA甲基转移酶DNMT1和DNMT3结构与功能的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2021-1589

摘要/Abstract

摘要：

DNA甲基转移酶是参与表观遗传修饰的重要蛋白家族。哺乳动物DNA甲基转移酶主要包括DNMT1、DNMT2、DNMT3A、DNMT3B和DNMT3L,其中,DNMT1、DNMT3A和DNMT3B可催化甲基转移至胞嘧啶第五位碳原子上,参与早期胚胎发育、生殖细胞发生、学习记忆、疾病发生等生物学过程。近年来,随着对DNA甲基化研究的不断深入,DNA甲基转移酶的作用机制受到科学工作者的广泛关注。该文从哺乳动物DNA甲基转移酶的结构特点、DNA甲基化的动态调节以及DNA甲基转移酶在个体发育和疾病发生中的作用等方面进行了综述。

关键词: DNA甲基转移酶, DNA甲基化, 结构, 个体发育, 疾病发生

Abstract:

The DNA methyltransferases are an important protein family involved in epigenetic modification,and DNMT1,DNMT2,DNMT3A,DNMT3B and DNMT3L are the main members in mammalian. Particularly,the methyl group are transferred to the fifth carbon atom of cytosine catalyzed by DNMT1,DNMT3A and DNMT3B,which are involved in numerous biological processes of early embryonic development,germ cell development,learning and memory,and disease occurrence. In recent years,with the development of the study on the DNA methylation,the mechanism of DNA methyltransferases has attracted extensive attention from scientists. In this paper,the structural characteristics of mammalian DNA methyltransferases,the dynamic regulation of mammalian DNA methylation,and the role of DNA methyltransferases in ontogeny and disease occurrence are reviewed.

Key words: DNA methyltransferases, DNA methylation, structural characteristics, ontogeny, disease occurrence

王晨晨, 张凡丽, 陈珮琪, 翁思瑶, 王慧芳, 崔小娟. 哺乳动物DNA甲基转移酶DNMT1和DNMT3结构与功能的研究进展[J]. 生物技术通报, 2022, 38(7): 31-39.

WANG Chen-chen, ZHANG Fan-li, CHEN Pei-qi, WENG Si-yao, WANG Hui-fang, CUI Xiao-juan. Research Progress in the Structural and Functional Analysis of Mammalian DNA Methyltransferase DNMT1 and DNMT3[J]. Biotechnology Bulletin, 2022, 38(7): 31-39.

图/表 3

图1 小鼠DNMTs蛋白家族的保守结构域

Fig.1 Conserved domains of mouse DNMTs protein family

图2 DNA甲基化模式的建立和维持

Fig. 2 Establishment and maintenance of DNA methylation patterns

图3 DNA甲基化的动态调节哺乳动物DNA甲基化由DNMTs建立和维持,DNA去甲基化包括：①被动去甲基化,DNA复制或参与DNA甲基化调节的酶缺失,可能使DNA发生被动去甲基化;②主动去甲基化：TETs参与DNA主动去甲基化过程,可将5mC依次氧化为5hmC、5fC和5caC。5fC和5caC在TDG的作用下参与BER途径,最终形成未被修饰的胞嘧啶

Fig. 3 Dynamic regulation of DNA methylation DNA methylation is established and maintained by DNMTs in mammalian. There are two pathways for DNA demethylation：1）passive dilution,i.e.,DNA replication or loss of enzymes participating in the dynamic regulation of DNA methylation may be involved in DNA demethylation;2）active demethylation,i.e.,TETs are involved in active DNA demethylation,which are successively oxidize 5mC to 5hmC,5fC and 5caC. Under the action of thymine DNA Glycosylase（TDG）,5fC and 5caC participate in the base excision repair（BER）pathway,converted to unmodified cytosine eventually

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