Vanyushin B F
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Biochemistry (Mosc). 2005 May;70(5):488-99. doi: 10.1007/s10541-005-0143-y.
In eukaryotic cells nuclear DNA is subjected to enzymatic methylation resulting in formation of 5-methylcytosine residues mainly in CG and CNG sequences. In plants and animals, this DNA methylation is species-, tissue-, and organelle-specific. It changes (diminishes) with age and is regulated by hormones. On the other hand, genome methylation can control hormonal signal. There are replicative and post-replicative DNA methylations. They are served by multiple DNA-methyltransferases with different site specificity. Replication is accompanied by appearance of hemi-methylated sites in DNA; pronounced asymmetry of DNA chain methylation disappears at the end of the cell cycle; a model of regulation of replication by DNA methylation is suggested. DNA methylation controls all genetic processes in the cell (replication, transcription, DNA repair, recombination, gene transposition) and it is a mechanism of cell differentiation, gene discrimination, and silencing. Prohibition of DNA methylation stops development (embryogenesis), switches on apoptosis, and is usually lethal. Distortions in DNA methylations result in cancerous cell transformation, and the DNA methylation pattern is one of the safe cancer diagnostics at early stages of carcinogenesis. The malignant cell has a different DNA methylation pattern and a set of DNA-methyltransferase activities expressed as compared with normal cells. Inhibition of DNA methylation in plants is accompanied by induction of genes of seed storage proteins and flowering. In eukaryotes one and the same gene can be methylated both on cytosine and adenine residues; thus, there are, at least, two different and probably interdependent systems of DNA methylation in the cell. First higher eukaryotic adenine DNA-methyltransferase was isolated from plants; this enzyme methylates DNA with formation of N6-methyladenine residues in the sequence TGATCA --> TGm6ATCA. Plants have AdoMet-dependent endonucleases sensitive to DNA methylation status; therefore, like microorganisms, plants seem to have a restriction-modification (R-S) system. Revelation of an essential role of DNA methylation in the regulation of genetic processes has laid a foundation for and materialized epigenetics and epigenomics.
在真核细胞中，核DNA会发生酶促甲基化，主要在CG和CNG序列中形成5-甲基胞嘧啶残基。在植物和动物中，这种DNA甲基化具有物种、组织和细胞器特异性。它会随着年龄增长而变化（减少），并受激素调节。另一方面，基因组甲基化可以控制激素信号。存在复制性和复制后DNA甲基化。它们由具有不同位点特异性的多种DNA甲基转移酶作用。复制过程中DNA会出现半甲基化位点；DNA链甲基化的明显不对称性在细胞周期结束时消失；有人提出了DNA甲基化调节复制的模型。DNA甲基化控制细胞中的所有遗传过程（复制、转录、DNA修复、重组、基因转座），它是细胞分化、基因识别和沉默的一种机制。禁止DNA甲基化会阻止发育（胚胎发生），开启细胞凋亡，通常是致命的。DNA甲基化的畸变会导致癌细胞转化，DNA甲基化模式是癌症早期安全诊断的指标之一。与正常细胞相比，恶性细胞具有不同的DNA甲基化模式和一组表达的DNA甲基转移酶活性。植物中DNA甲基化的抑制伴随着种子储存蛋白基因和开花基因的诱导。在真核生物中，同一个基因的胞嘧啶和腺嘌呤残基都可能被甲基化；因此，细胞中至少存在两种不同且可能相互依赖的DNA甲基化系统。首个高等真核生物腺嘌呤DNA甲基转移酶是从植物中分离出来的；这种酶使DNA甲基化，在序列TGATCA --> TGm6ATCA中形成N6-甲基腺嘌呤残基。植物具有对DNA甲基化状态敏感的依赖于腺苷甲硫氨酸的核酸内切酶；因此，与微生物一样，植物似乎具有限制修饰（R-S）系统。揭示DNA甲基化在遗传过程调控中的重要作用为表观遗传学和表观基因组学奠定了基础并使其得以实现。
