Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.
Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.
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DOI：
10.1016/j.ygeno.2011.06.003
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发表时间：
2011-09
期刊：
影响因子：
4.4
通讯作者：
Hideyuki Takeshima;S. Yamashita;T. Shimazu;T. Ushijima
中科院分区：
文献类型：
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作者：
Hideyuki Takeshima;S. Yamashita;T. Shimazu;T. Ushijima
与突变相反，异常DNA甲基化在特定启动子CpG岛（CGI）处诱导。其特异性受基因组结构和表观遗传因素的影响，但它们之间的关系尚不清楚。在这项研究中，我们分离启动子CGIs敏感和抵抗异常甲基化诱导在前列腺和乳腺癌的发生。基因组结构的影响是更明显的启动子CGIs敏感的两个组织比启动子CGIs敏感的只有一个组织。启动子CGIs与组织非特异性易感性的多变量分析表明，基因组结构，即SINE的远程位置，（OR=5.98; 95% CI=2.33-15.34）和LINE（OR=2.08; 95%CI =1.03-4.21），与易感性增加相关，独立于表观遗传因素，如RNA聚合酶II的存在（OR=0.09; 95%CI =0.02-0.48）和H3K27me3（OR=3.28; 95%CI =1.17-9.21）。这些结果表明启动子CGIs的甲基化易感性是由基因组结构和表观遗传因素独立决定的。
Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolated promoter CGIs susceptible and resistant to aberrant methylation induction during prostate and breast carcinogenesis. The effect of genome architecture was more evident for promoter CGIs susceptible in both of the two tissues than for promoter CGIs susceptible only in one tissue. Multivariate analysis of promoter CGIs with tissue-nonspecific susceptibility showed that genome architecture, namely a remote location from SINE (OR=5.98; 95% CI=2.33–15.34) and from LINE (OR=2.08; 95% CI=1.03–4.21), was associated with increased susceptibility, independent of epigenetic factors such as the presence of RNA polymerase II (OR=0.09; 95% CI=0.02–0.48) and H3K27me3 (OR=3.28; 95% CI=1.17–9.21). These results showed that methylation susceptibility of promoter CGIs is determined both by genome architecture and epigenetic factors, independently.