DNA motifs associated with aberrant CpG island methylation
DNA motifs associated with aberrant CpG island methylation
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DOI：
10.1016/j.ygeno.2005.12.016
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发表时间：
2006-05-01
期刊：
影响因子：
4.4
通讯作者：
Vertino, Paula M.
中科院分区：
文献类型：
--
作者：
Feltus, F. Alex;Lee, Eva K.;Vertino, Paula M.
涉及启动子区域CpG岛异常甲基化的表观遗传沉默被广泛认为是癌症中的肿瘤抑制沉默机制。然而，异常DNA甲基化的分子途径仍然难以捉摸。最近，我们发现，在全基因组水平上，CpG岛基因座在其对异常甲基化的内在易感性方面存在差异，并且这种易感性可以根据潜在的序列背景进行预测。这些数据表明，有序列/结构特征，有助于保护或异常甲基化的易感性。在这里，我们使用基序引出结合分类技术，以确定DNA序列的基序，选择性地定义甲基化倾向或甲基化抗性的CpG岛。使用MEME和MAST算法（http：//www.example.com）确定28个甲基化倾向或47个甲基化抗性CpG岛的基因组片段共有的基序。meme.sdsc.edu来自甲基化倾向序列的五个最具歧视性的基序通常与CpG岛相关，并且在整个基因组中非随机分布。相比之下，来自甲基化抗性CpG岛的8个最具歧视性的基序随机分布在整个基因组中。有趣的是，后一组倾向于与Alu和其他重复序列相关。一起使用，这些基序的出现频率成功区分甲基化倾向和甲基化抗性CpG岛组，10倍交叉验证后的准确率为87%。这里鉴定的基序是候选的甲基化靶向或甲基化保护DNA序列。(c)2005年爱思唯尔公司All rights reserved.
Epigenetic silencing involving the aberrant methylation of promoter region CpG islands is widely recognized as a tumor suppressor silencing mechanism in cancer. However, the molecular pathways underlying aberrant DNA methylation remain elusive. Recently we showed that, on a genome-wide level, CpG island loci differ in their intrinsic susceptibility to aberrant methylation and that this susceptibility can be predicted based on underlying sequence context. These data suggest that there are sequence/structural features that contribute to the protection from or susceptibility to aberrant methylation. Here we use motif elicitation coupled with classification techniques to identify DNA sequence motifs that selectively define methylation-prone or methylation-resistant CpG islands. Motifs common to 28 methylation-prone or 47 methylation-resistant CpG island-containing genomic fragments were determined using the MEME and MAST algorithms (http://meme.sdsc.edu). The five most discriminatory motifs derived from methylation-prone sequences were found to be associated with CpG islands in general and were nonrandomly distributed throughout the genome. In contrast, the eight most discriminatory motifs derived from the methylation-resistant CpG islands were randomly distributed throughout the genome. Interestingly, this latter group tended to associate with Alu and other repetitive sequences. Used together, the frequency of occurrence of these motifs successfully discriminated methylation-prone and methylation-resistant CpG island groups with an accuracy of 87% after 10-fold cross-validation. The motifs identified here are candidate methylation-targeting or methylation-protection DNA sequences. (c) 2005 Elsevier Inc. All rights reserved.