前列腺癌启动子非 CG 甲基化分析。
Analysis of promoter non-CG methylation in prostate cancer.
机构信息
Department of Urology, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
出版信息
Epigenomics. 2013 Feb;5(1):65-71. doi: 10.2217/epi.12.67.
BACKGROUND
In vertebrates, DNA methylation occurs primarily at CG dinucleotides but recently, non-CG methylation has been found at appreciable levels in embryonic stem cells.
MATERIALS & METHODS: To assess non-CG methylation in cancer, we compared the extent of non-CG methylation at several biologically important CG islands in prostate cancer and normal cell lines. An assessment of the promoter CG islands EVX1 and FILIP1L demonstrates a fourfold higher rate of non-CG methylation at EVX1 compared with FILIP1L across all cell lines. These loci are densely methylated at CG sites in cancer.
RESULTS
No significant difference in non-CG methylation was demonstrated between cancer and normal. Treatment of cancer cell lines with 5-azacytidine significantly reduced methylation within EVX1 at CG and CC sites, preferentially.
CONCLUSION
Non-CG methylation does not correlate with CG methylation at hypermethylated promoter regions in cancer. Furthermore, global inhibition of DNA methyltransferases does not affect all methylated cytosines uniformly.
背景
在脊椎动物中，DNA 甲基化主要发生在 CG 二核苷酸上，但最近在胚胎干细胞中发现了相当水平的非 CG 甲基化。
材料与方法
为了评估癌症中的非 CG 甲基化，我们比较了前列腺癌和正常细胞系中几个生物学上重要的 CG 岛的非 CG 甲基化程度。对启动子 CG 岛 EVX1 和 FILIP1L 的评估表明，在所有细胞系中，EVX1 的非 CG 甲基化率比 FILIP1L 高四倍。这些基因座在癌症中 CG 位点高度甲基化。
结果
在癌症和正常组织之间未显示非 CG 甲基化存在显著差异。用 5-氮杂胞苷处理癌细胞系，可显著降低 EVX1 中 CG 和 CC 位点的甲基化，优先降低。
结论
非 CG 甲基化与癌症中高甲基化启动子区域的 CG 甲基化无关。此外，DNA 甲基转移酶的全局抑制不会均匀地影响所有甲基化的胞嘧啶。
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