Kruczek I, Doerfler W
EMBO J. 1982;1(4):409-14. doi: 10.1002/j.1460-2075.1982.tb01183.x.
An inverse correlation has been established between the levels of DNA methylation at 5'-CCGG-3' (MspI/HpaII) sites in specific genes of integrated viral DNA in adenovirus type 12 (Ad12)-transformed hamster cell lines and the extent to which these genes are expressed ( Sutter and Doerfler , 1979, 1980). In general, early genes are transcribed into mRNA, while late genes are permanently switched off in these cell lines. Adenovirus type 2 genes methylated in vitro at 5'-CCGG-3' sites are not transcribed upon microinjection into nuclei of Xenopus laevis oocytes - unmethylated genes are expressed ( Vardimon et al., 1982a ). The MspI sites in the early and in some of the late Ad12 genes in cell lines HA12 /7, T637 , and A2497 -3 have now been precisely mapped. The data presented here reveal that the promoter/leader and 5'-regions of the early genes are unmethylated both at MspI sites and at 5'-GCGC-3' (HhaI) sites. In some instances, e.g., in the E2a regions in all three lines, the main parts of the early genes are partly methylated, even though the genes are expressed. In cell line HA12 /7, the early region E3 is not expressed, and the promoter/leader and 5'-regions of this segment are fully methylated. All late regions are completely methylated. The results suggest that the state of methylation in the promoter/leader and 5'-regions of integrated adenovirus genes is important in the control of gene expression.
在12型腺病毒（Ad12）转化的仓鼠细胞系中，整合病毒DNA特定基因的5'-CCGG-3'（MspI/HpaII）位点的DNA甲基化水平与这些基因的表达程度之间已建立起负相关关系（萨特和多弗勒，1979年，1980年）。一般来说，早期基因被转录成mRNA，而晚期基因在这些细胞系中则永久关闭。在体外于5'-CCGG-3'位点甲基化的2型腺病毒基因，在显微注射到非洲爪蟾卵母细胞核后不被转录——未甲基化的基因则会表达（瓦尔迪蒙等人，1982a）。现已精确绘制出细胞系HA12 /7、T637和A2497 -3中早期和部分晚期Ad12基因的MspI位点。此处呈现的数据表明，早期基因的启动子/前导序列和5'-区域在MspI位点以及5'-GCGC-3'（HhaI）位点均未甲基化。在某些情况下，例如在所有三个细胞系的E2a区域，即使这些基因表达，其早期基因的主要部分也部分甲基化。在细胞系HA12 /7中，早期区域E3不表达，该片段的启动子/前导序列和5'-区域完全甲基化。所有晚期区域均完全甲基化。结果表明，整合腺病毒基因的启动子/前导序列和5'-区域的甲基化状态在基因表达调控中很重要。
