Fidelity of the methylation pattern and its variation in the genome
Fidelity of the methylation pattern and its variation in the genome
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DOI：
10.1101/gr.969603
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发表时间：
2003-05-01
期刊：
影响因子：
7
通讯作者：
Miyamoto, K
中科院分区：
文献类型：
--
作者：
Ushijima, T;Watanabe, N;Miyamoto, K
CpG位点的甲基化或非甲基化状态被忠实地从父母DNA复制到女儿DNA，并起到细胞记忆的作用。然而，没有关于非甲基化CpG岛(CGI)的甲基化模式的保真度或其在基因组中的变异的信息。在这里，我们确定了从正常人类乳腺上皮细胞克隆群体中获得的每个DNA分子上每个CpG位点的甲基化状态。甲基化模式错误率(MPERS)是基于与甲基化模式的偏差计算的，如果细胞在复制甲基化模式时具有100%的保真度，则应获得该偏差。5个基因启动子区域的未甲基化CGI的mPER为0.018~0.032个/位/代，甲基化模式的保真度为99.85%~99.92%/位/代。相比之下，启动子区域以外的未甲基化CGI显示mPERS高出两倍以上(P<；0.01)。甲基化区域，包括MAGE-A3启动子的CGI和H19基因的DMR，显示出比未甲基化的CGI低得多的mPERS。这表明甲基化模式中的错误主要是由于未甲基化区域的从头甲基化。即使在未甲基化的CGI之间的差异mPERS也表明存在启动子特异性的保护机制(S)，使其免受从头甲基化的影响。
The methylated or unmethylated status of a CpG site is copied faithfully from parental DNA to daughter DNA, and functions as a cellular memory. However, no information is available for the fidelity of methylation pattern in unmethylated CpG islands (CGIs) or its variation in the genome. Here, we determined the methylation status of each CpG site on each DNA molecule obtained from clonal populations of normal human mammary epithelial cells. Methylation pattern error rates (MPERs) were calculated based upon the deviation from the methylation patterns that should be obtained if the cells had 100% fidelity in replicating the methylation pattern. Unmethylated CGIs in the promoter regions of five genes showed MPERs of 0.018-0.032 errors/site/21.6 generations, and the fidelity of methylation pattern was calculated as 99.85%-99.92%/site/generation. In contrast, unmethylated CGIs outside the promoter regions showed MPERs more than twice as high (P < 0.01). Methylated regions, including a CGI in the MAGE-A3 promoter and DMR of the H19 gene, showed much lower MPERs than unmethylated CGIs. These showed that errors in methylation pattern were mainly due to de novo methylations in unmethylated regions. The differential MPERs even among unmethylated CGIs indicated that a promoter-specific protection mechanism(s) from de novo methylation was present.