Genome-wide profiling of DNA methylation in human cancer cells
Genome-wide profiling of DNA methylation in human cancer cells
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DOI：
10.1016/j.ygeno.2011.07.003
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发表时间：
2011-10-01
期刊：
影响因子：
4.4
通讯作者：
Matsushima, Kouji
中科院分区：
文献类型：
--
作者：
Ogoshi, Katsumi;Hashimoto, Shin-ichi;Matsushima, Kouji
DNA甲基化的整体变化与癌症中基因表达改变和基因组不稳定性相关。我们开发了一种甲基化特异性数字测序（MSDS）方法，可以在基因组规模上评估DNA甲基化。MSDS是一种简单、低成本的方法，它结合了甲基化敏感性限制性内切酶和第二代测序技术的使用。使用MSDS测量两种结肠癌细胞系HT 29和HCT 116中的DNA甲基化。当比较两种细胞系之间的甲基化水平时，在CpG岛海岸区域（位于CpG岛2 kb内）、基因体区域和基因间区域中鉴定出许多差异甲基化区域（DMR）。基因转录起始位点附近的DMR数量与TACC1、CLDN1和PLEKHC1（FERMT2）基因的表达水平相关，这些基因与致癌作用有关。MSDS方法有可能为人类基因组的功能复杂性提供新的见解。(C)2011 Elsevier Inc. All rights reserved.
Global changes in DNA methylation correlate with altered gene expression and genomic instability in cancer. We have developed a methylation-specific digital sequencing (MSDS) method that can assess DNA methylation on a genomic scale. MSDS is a simple, low-cost method that combines the use of methylation-sensitive restriction enzymes with second generation sequencing technology. DNA methylation in two colon cancer cell lines, HT29 and HCT116, was measured using MSDS. When methylation levels were compared between the two cell lines, many differentially methylated regions (DMRs) were identified in CpG island shore regions (located within 2 kb of a CpG island), gene body regions and intergenic regions. The number of DMRs in the vicinity of gene transcription start sites correlated with the level of expression of TACC1, CLDN1, and PLEKHC1 (FERMT2) genes, which have been linked to carcinogenesis. The MSDS method has the potential to provide novel insight into the functional complexity of the human genome. (C) 2011 Elsevier Inc. All rights reserved.