Nagase Hiroki, Ghosh Srimoyee
Advanced Research Institute for the Sciences and Humanities, Nihon University, 12-5 Goban-cho, Chiyoda-ku, Tokyo, Japan.
FEBS J. 2008 Apr;275(8):1617-23. doi: 10.1111/j.1742-4658.2008.06330.x. Epub 2008 Mar 7.
Epigenetics refers to heritable phenotypic alterations in the absence of DNA sequence changes, and DNA methylation is one of the extensively studied epigenetic alterations. DNA methylation is an evolutionally conserved mechanism to regulate gene expression in mammals. Because DNA methylation is preserved during DNA replication it can be inherited. Thus, DNA methylation could be a major mechanism by which to produce semi-stable changes in gene expression in somatic tissues. Although it remains controversial whether germ-line DNA methylation in mammalian genomes is stably heritable, frequent tissue-specific and disease-specific de novo methylation events are observed during somatic cell development/differentiation. In this minireview, we discuss the use of restriction landmark genomic scanning, together with in silico analysis, to identify differentially methylated regions in the mammalian genome. We then present a rough overview of quantitative DNA methylation patterns at 4600 NotI sites and more than 150 differentially methylated regions in several C57BL/6J mouse tissues. Comparative analysis between mice and humans suggests that some, but not all, tissue-specific differentially methylated regions are conserved. A deeper understanding of cell-type-specific differences in DNA methylation might lead to a better illustration of the mechanisms behind tissue-specific differentiation in mammals.
表观遗传学是指在DNA序列没有变化的情况下可遗传的表型改变,而DNA甲基化是一种被广泛研究的表观遗传改变。DNA甲基化是哺乳动物中调控基因表达的一种进化上保守的机制。由于DNA甲基化在DNA复制过程中得以保留,所以它能够被遗传。因此,DNA甲基化可能是在体细胞组织中产生基因表达半稳定变化的主要机制。尽管哺乳动物基因组中的生殖系DNA甲基化是否能稳定遗传仍存在争议,但在体细胞发育/分化过程中经常会观察到频繁的组织特异性和疾病特异性从头甲基化事件。在这篇小型综述中,我们讨论了如何结合计算机分析使用限制性内切酶位点基因组扫描来鉴定哺乳动物基因组中差异甲基化区域。然后,我们大致概述了几种C57BL/6J小鼠组织中4600个NotI位点以及150多个差异甲基化区域的定量DNA甲基化模式。小鼠和人类之间的比较分析表明,一些(但不是全部)组织特异性差异甲基化区域是保守的。对DNA甲基化中细胞类型特异性差异有更深入的了解可能有助于更好地阐明哺乳动物组织特异性分化背后的机制。