A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q
A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q
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DOI：
10.1101/gr.1351604
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发表时间：
2004-02-01
期刊：
影响因子：
7
通讯作者：
Ito, T
中科院分区：
文献类型：
--
作者：
Yamada, Y;Watanabe, H;Ito, T
大约一半的人类基因在其启动子区域周围具有CpG岛（CGI）。虽然CGIs通常逃脱甲基化，但女性X染色体上的CGIs和印迹基因附近的CGIs是例外：它们具有甲基化和未甲基化的等位基因，在甲基化分析中显示“复合”模式。此外，已知CGI的异常甲基化经常发生在癌细胞中。在这里，我们开发了一种简单的Hpall-McrBC PCR方法，用于区分完全，无效，不完全和复合甲基化模式，并将其应用于人类染色体21 q上所有计算鉴定的CGIs。这项综合分析显示，尽管大多数CGIs（149个中的103个）逃避甲基化，但即使在正常外周血细胞中，也有相当大的一部分（149个中的31个）完全甲基化。此外，我们确定了七个CGIs显示复合甲基化，并证明其中三个确实是甲基化单等位基因。进一步的分析，使用信息系谱显示，三个中的两个受到母体等位基因特异性甲基化。有趣的是，另一个CGI以等位基因特异性但不依赖于亲本来源的方式甲基化。因此，细胞似乎具有比以前认为的更广泛的甲基化CGIs的库，并且我们的方法可能有助于揭示等位基因甲基化的新模式。
Approximately half of all human genes have CpG islands (CGIs) around their promoter regions. Although CGIs usually escape methylation, those on Chromosome X in females and those in the vicinity of imprinted genes are exceptions: They have both methylated and unmethylated alleles to display a "composite" pattern in methylation analysis. In addition, aberrant methylation of CGIs is known to often occur in cancer cells. Here we developed a simple Hpall-McrBC PCR method for discrimination of full, null, incomplete, and composite methylation patterns, and applied it to all computationally identified CGIs on human Chromosome 21q. This comprehensive analysis revealed that, although most CGIs (103 out of 149) escape methylation, a sizable fraction (31 out of 149) are fully methylated even in normal peripheral blood cells. Furthermore, we identified seven CGIs showing the composite methylation, and demonstrated that three of them are indeed methylated monoallelically. Further analyses using informative pedigrees revealed that two of the three are subject to maternal allele-specific methylation. Intriguingly, the other CGI is methylated in an allele-specific but parental-origin-independent manner. Thus, the cell seems to have a broader repertoire of methylating CGIs than previously thought, and our approach may contribute to uncover novel modes of allelic methylation.