Vaniushin B F
Genetika. 2006 Sep;42(9):1186-99.
In eukaryotic cells, nuclear DNA is subject to enzymatic methylation with the formation of 5-methylcytosine residues, mostly within the CG and CNG sequences. In plants and animals this DNA methylation is species-, tissue-, and organelle-specific. It changes (decreases) with age and is regulated by hormones. On the other hand, genome methylation can control hormonal signal. Replicative and post-replicative DNA methylation types are distinguished. They are mediated by multiple DNA methyltransferases with different site-specificity. Replication is accompanied by the appearance of hemimethylated DNA sites. Pronounced asymmetry of the DNA strand methylation disappears to the end of the cell cycle. A model of methylation-regulated DNA replication is proposed. DNA methylation controls all genetic processes in the cell (replication, transcription, DNA repair, recombination, and gene transposition). It is the mechanism of cell differentiation, gene discrimination and silencing. In animals, suppression of DNA methylation stops development (embryogenesis), switches on apoptosis, and is usually lethal. Disruption of DNA methylation pattern results in the malignant cell transformation and serves as one of the early diagnostic features of carcinogenesis. In malignant cell the pattern of DNA methylation, as well as the set of DNA methyltransferase activities, differs from that in normal cell. In plants inhibition of DNA methylation is accompanied by the induction of seed storage and florescence genes. In eukaryotes one and the same gene can be simultaneously methylated both at cytosine and adenine residues. It can be thus suggested, that the plant cell contains at least two different, and probably, interdependent systems of DNA methylation. The first eukaryotic adenine DNA methyltransferase was isolated from plants. This enzyme methylates DNA with the formation of N6-methyladenine residues in the sequence TGATCA (TGATCA-->TGm6ATCA). Plants possess AdoMet-dependent endonucleases sensitive to DNA methylation. It seems likely that plants, similarly to microorganisms and some lower eukaryotes, have restriction--modification (R--M) system. Discovery of the essential role of DNA methylation in regulation of genetic processes served as a principle basis and materialization of epigenetics and epigenomics.
在真核细胞中,核DNA会发生酶促甲基化,形成5-甲基胞嘧啶残基,主要存在于CG和CNG序列中。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。可区分复制性和复制后DNA甲基化类型。它们由具有不同位点特异性的多种DNA甲基转移酶介导。复制过程伴随着半甲基化DNA位点的出现。DNA链甲基化的明显不对称性在细胞周期结束时消失。提出了甲基化调节DNA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、重组和基因转座)。它是细胞分化、基因识别和沉默的机制。在动物中,DNA甲基化的抑制会阻止发育(胚胎发生),引发细胞凋亡,通常是致命的。DNA甲基化模式的破坏会导致恶性细胞转化,并作为致癌作用的早期诊断特征之一。在恶性细胞中,DNA甲基化模式以及DNA甲基转移酶活性集与正常细胞不同。在植物中,DNA甲基化的抑制伴随着种子储存和开花基因的诱导。在真核生物中,同一个基因可以同时在胞嘧啶和腺嘌呤残基处发生甲基化。因此可以推测,植物细胞至少含有两种不同且可能相互依赖的DNA甲基化系统。首个真核生物腺嘌呤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(TGATCA→TGm6ATCA)中形成N6-甲基腺嘌呤残基。植物拥有对DNA甲基化敏感的依赖于腺苷甲硫氨酸的核酸内切酶。植物似乎与微生物和一些低等真核生物类似,具有限制-修饰(R-M)系统。DNA甲基化在遗传过程调控中重要作用的发现是表观遗传学和表观基因组学的原理基础和具体体现。