Razin A, Webb C, Szyf M, Yisraeli J, Rosenthal A, Naveh-Many T, Sciaky-Gallili N, Cedar H
Proc Natl Acad Sci U S A. 1984 Apr;81(8):2275-9. doi: 10.1073/pnas.81.8.2275.
Mouse teratocarcinoma cells induced to differentiate in vitro undergo a massive (30%) demethylation of DNA. A similar undermethylation is also observed in the mouse extraembryonic membranes, the yolk sac and placenta. In both cases, the decrease in methyl moieties occurs at a large number of CpG sites spread out over the entire genome, as indicated by a restriction enzyme analysis of several mouse genes including dhfr, beta-major globin, and the H-2K gene family. In contrast to this, the embryo itself appears to undergo methylation de novo during early stages of embryogenesis. Thus, as opposed to somatic cells, events during early mouse development are associated with wide variations in the level of DNA methylation. Although these changes in DNA methylation seem to be an integral part of the differentiation process, its relation to specific gene expression is still unclear.
体外诱导分化的小鼠畸胎瘤细胞会经历大规模（30%）的DNA去甲基化。在小鼠的胚外膜、卵黄囊和胎盘中也观察到了类似的低甲基化现象。在这两种情况下，甲基部分的减少发生在遍布整个基因组的大量CpG位点上，这通过对包括二氢叶酸还原酶（dhfr）、β-珠蛋白和H-2K基因家族在内的多个小鼠基因进行限制性酶切分析得以表明。与此形成对比的是，胚胎自身在胚胎发育早期似乎会发生从头甲基化。因此，与体细胞不同，小鼠早期发育过程中的事件与DNA甲基化水平的广泛变化相关。尽管DNA甲基化的这些变化似乎是分化过程中不可或缺的一部分，但其与特定基因表达的关系仍不清楚。
