Searle S, Gillespie D A, Chiswell D J, Wyke J A
Nucleic Acids Res. 1984 Jul 11;12(13):5193-210. doi: 10.1093/nar/12.13.5193.
Cells of the A11 lineage of Rat-1 contain a single complete Rous sarcoma provirus. Variation in the activity of this provirus accompanies fluctuations in the lineage between normal and transformed phenotypes. Increased proviral cytosine methylation of the doublet CpG in the tetranucleotide CCGG correlates with transcriptional inactivity and this pattern of cytosine hypermethylation is stable, even when the cells are transformed by another virus. However, transformation can also be induced by 5-azacytidine (but not by other mutagens) and in these transformants reduced proviral cytosine methylation is accompanied by increased proviral transcription. Differences in CCGG methylation between normal and transformed cells are found mainly in the 3' half of the provirus; sites near and within the src gene are heavily methylated only when the provirus is transcriptionally inactive. On the other hand, both transformed and normal A11 derivatives show little, if any, cytosine methylation of CCGG sequences in and flanking the 5' portion of the provirus.
大鼠-1细胞系的A11细胞含有一个完整的劳氏肉瘤前病毒。该前病毒活性的变化伴随着细胞系在正常和转化表型之间的波动。四核苷酸CCGG中双峰CpG的前病毒胞嘧啶甲基化增加与转录无活性相关,并且这种胞嘧啶高甲基化模式是稳定的,即使细胞被另一种病毒转化也是如此。然而,5-氮杂胞苷(而非其他诱变剂)也能诱导转化,在这些转化体中,前病毒胞嘧啶甲基化减少伴随着前病毒转录增加。正常细胞和转化细胞之间CCGG甲基化的差异主要存在于前病毒的3'端;只有当前病毒转录无活性时,src基因附近和内部的位点才会高度甲基化。另一方面,无论是转化的还是正常的A11衍生物,在前病毒5'端及其侧翼的CCGG序列中,胞嘧啶甲基化很少(如果有的话)。