DNA methylation: past, present and future directions
DNA methylation: past, present and future directions
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DOI：
10.1093/carcin/21.3.461
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发表时间：
2000-03-01
期刊：
影响因子：
4.7
通讯作者：
Jones, PA
中科院分区：
文献类型：
--
作者：
Robertson, KD;Jones, PA
DNA甲基化，或在CpG二核苷酸的背景下将甲基共价添加到胞嘧啶，对哺乳动物基因组具有深远的影响。这些效应包括通过抑制转录因子结合或甲基结合蛋白及其相关染色质重塑因子的募集、X染色体失活、印记和抑制寄生DNA序列来抑制转录。DNA甲基化对于胚胎的正常发育也是必不可少的;然而，它的存在会给基因组增加额外的负担。正常的甲基化模式在肿瘤细胞中经常被破坏，伴随着区域特异性高甲基化的整体低甲基化。当这些超甲基化事件发生在肿瘤抑制基因的启动子内时，它们将使该基因沉默，并以类似于缺失或突变的方式为细胞提供生长优势。最近的工作表明，DNA甲基化是DNA修复和基因组稳定性的重要参与者，以及一个新的DNA甲基转移酶家族的发现，使甲基化领域现在一个非常令人兴奋的时期。这篇综述将突出甲基化领域在过去20年中的主要发现，然后总结该领域在下一个千年中可能采取的最重要和最有趣的未来方向。
DNA methylation, or the covalent addition of a methyl group to cytosine within the context of the CpG dinucleotide, has profound effects on the mammalian genome. These effects include transcriptional repression via inhibition of transcription factor binding or the recruitment of methyl-binding proteins and their associated chromatin remodeling factors, X chromosome inactivation, imprinting and the suppression of parasitic DNA sequences. DNA methylation is also essential for proper embryonic development; however, its presence can add an additional burden to the genome. Normal methylation patterns are frequently disrupted in tumor cells with global hypomethylation accompanying region-specific hypermethylation. When these hypermethylation events occur within the promoter of a tumor suppressor gene they will silence the gene and provide the cell with a growth advantage in a manner akin to deletions or mutations. Recent work indicating that DNA methylation is an important player in both DNA repair and genome stability as well as the discovery of a new family of DNA methyltransferases makes now a very exciting period for the methylation field. This review will highlight the major findings in the methylation field over the past 20 years then summarize the most important and interesting future directions the field is likely to take in the next millennium.