Jones P A
Department of Biochemistry and Molecular Biology, University of Southern, California/Norris Comprehensive Cancer Center and Hospital, Los Angeles 90033-0800, USA.
Trends Genet. 1999 Jan;15(1):34-7. doi: 10.1016/s0168-9525(98)01636-9.
The methylation of CpG islands is often equated with transcriptional inactivity and there is overwhelming evidence that this is the case for islands located in gene promoters. Such methylation is probably part of a mechanism to permanently silence the activities of genes, including those on the inactive X chromosome. Not all CpG islands and methylation sites are located in known promoters; several tissue-specific and imprinted genes have CpG islands located at considerable distances downstream of transcription initiation sites, and many genes have multiple promoters. Methylation of CpG islands downstream of transcription initiation does not block elongation in mammalian cells. This has given rise to an interesting paradox in which methylation in the transcribed region is often correlated with expression, in contrast to the inverse correlation seen at the site of transcriptional initiation. The methylation paradox might be resolved if it is hypothesized that transcription through a CpG island facilitates de novo methylation.
CpG岛的甲基化常被等同于转录不活性，并且有大量证据表明位于基因启动子区域的岛确实如此。这种甲基化可能是一种使基因活性永久沉默的机制的一部分，包括那些位于失活X染色体上的基因。并非所有的CpG岛和甲基化位点都位于已知的启动子区域；一些组织特异性基因和印记基因的CpG岛位于转录起始位点下游相当远的位置，而且许多基因有多个启动子。转录起始位点下游的CpG岛甲基化不会阻断哺乳动物细胞中的延伸。这就产生了一个有趣的悖论：与转录起始位点处的负相关相反，转录区域的甲基化常常与表达相关。如果假设通过CpG岛的转录促进从头甲基化，那么甲基化悖论或许可以得到解决。
