Hsiao W L, Gattoni-Celli S, Kirschmeier P, Weinstein I B
Mol Cell Biol. 1984 Apr;4(4):634-41. doi: 10.1128/mcb.4.4.634-641.1984.
The present study indicates that the transient exposure of C3H 10T1/2 mouse embryo fibroblasts to 5-azacytidine leads to extensive loss of methylation of the protooncogene c-mos and the beta-globin locus at the cell population level and in at least 40 isolated subclones. These changes persisted, even when the cells were serially passaged for many generations without further exposure to the drug. Even though the amount of demethylation, assessed through differential digestion by the restriction enzymes HpaII and MspI, was quite extensive, neither locus was transcribed at a detectable level. This nonselective analysis suggests, therefore, that loss of DNA methylation is not sufficient per se to induce the expression of certain loci. Presumably, the expression of these loci requires additional factors, some of which may be related to cell lineage and differentiation.
本研究表明，将C3H 10T1/2小鼠胚胎成纤维细胞短暂暴露于5-氮杂胞苷，会导致原癌基因c-mos和β-珠蛋白基因座在细胞群体水平以及至少40个分离的亚克隆中发生广泛的甲基化缺失。即使细胞连续传代许多代且不再进一步接触该药物，这些变化仍然持续存在。尽管通过限制性内切酶HpaII和MspI的差异消化评估的去甲基化程度相当广泛，但两个基因座均未在可检测水平转录。因此，这种非选择性分析表明，DNA甲基化的缺失本身不足以诱导某些基因座的表达。据推测，这些基因座的表达需要其他因素，其中一些因素可能与细胞谱系和分化有关。
