USC Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, California 90089-99176, USA.
Nat Rev Genet. 2012 May 29;13(7):484-92. doi: 10.1038/nrg3230.
DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.
DNA 甲基化通常被描述为一种“沉默”的表观遗传标记,事实上,5-甲基胞嘧啶的这一功能最初是在 20 世纪 70 年代提出的。现在,由于对甲基化的全基因组规模图谱绘制技术的改进,我们可以在不同的基因组环境中评估 DNA 甲基化:转录起始位点是否带有 CpG 岛、在基因体中、在调控元件中和在重复序列中。目前的情况表明,DNA 甲基化的功能似乎与其所处的环境有关,而且 DNA 甲基化与转录之间的关系比我们最初意识到的更为复杂。为了理解在癌症等疾病中观察到的这种标记的变化,我们有必要提高对 DNA 甲基化功能的认识。