Michalowsky L A, Jones P A
Department of Biochemistry, USC Cancer Center, Los Angeles 90033.
Environ Health Perspect. 1989 Mar;80:189-97. doi: 10.1289/ehp.8980189.
The methylation of specific cytosine residues in DNA has been implicated in regulating gene expression and facilitating functional specialization of cellular phenotypes. Generally, the demethylation of certain CpG sites correlates with transcriptional activation of genes. 5-Azacytidine is an inhibitor of DNA methylation and has been widely used as a potent activator of suppressed genetic information. Treatment of cells with 5-azacytidine results in profound phenotypic alterations. The drug-induced hypomethylation of DNA apparently perturbs DNA-protein interactions that may consequently alter transcriptional activity and cell determination. The inhibitory effect of cytosine methylation may be exerted via altered DNA-protein interactions specifically or may be transduced by a change in the conformation of chromatin. Recent studies have demonstrated that cytosine methylation also plays a central role in parental imprinting, which in turn determines the differential expression of maternal and paternal genomes during embryogenesis. In other words, methylation is the mechanism whereby the embryo retains memory of the gametic origin of each component of genetic information. A memory of this type would probably persist during DNA replication and cell division as methylation patterns are stable and heritable.
DNA中特定胞嘧啶残基的甲基化与调节基因表达及促进细胞表型的功能特化有关。一般来说，某些CpG位点的去甲基化与基因的转录激活相关。5-氮杂胞苷是一种DNA甲基化抑制剂，已被广泛用作抑制遗传信息的有效激活剂。用5-氮杂胞苷处理细胞会导致深刻的表型改变。药物诱导的DNA低甲基化显然会扰乱DNA-蛋白质相互作用，进而可能改变转录活性和细胞分化。胞嘧啶甲基化的抑制作用可能通过特异性改变DNA-蛋白质相互作用来发挥，或者可能由染色质构象的变化传导。最近的研究表明，胞嘧啶甲基化在亲本印记中也起着核心作用，而亲本印记又决定了胚胎发育过程中母本和父本基因组的差异表达。换句话说，甲基化是胚胎保留遗传信息各组成部分配子起源记忆的机制。由于甲基化模式稳定且可遗传，这种类型的记忆可能在DNA复制和细胞分裂过程中持续存在。
