Dynamic changes in DNA methylation patterns in canine lymphoma cell lines demonstrated by genome-wide quantitative DNA methylation analysis.
Dynamic changes in DNA methylation patterns in canine lymphoma cell lines demonstrated by genome-wide quantitative DNA methylation analysis.
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通过基因组定量DNA甲基化分析证明的犬淋巴瘤细胞系中DNA甲基化模式的动态变化。
DOI：
10.1016/j.tvjl.2017.11.007
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Inaba M
中科院分区：
文献类型：
--
作者：
Yamazaki J;Jelinek J;Hisamoto S;Tsukamoto A;Inaba M
DNA甲基化是胞嘧啶转化为5-甲基胞嘧啶，导致DNA和蛋白质之间相互作用的变化。胞嘧啶-鸟嘌呤（CpG）岛（CGI）的甲基化与相关启动子的基因表达沉默相关。尽管在患有某些疾病的狗中进行了专注于DNA甲基化的整体变化或几个单一位点的研究，但需要对DNA甲基化进行全基因组分析以前瞻性地识别具有DNA甲基化变化的特定区域。本研究的假设是，通过用SmaI和XmaI酶连续消化基因组DNA产生的甲基化特异性特征的下一代测序可以提供甲基化水平的定量信息。使用来自健康犬的血液和从犬淋巴瘤细胞系获得的细胞，使用本研究中建立的新方法分析了犬基因组中约100，000个CpG位点。CGIs中的CpG位点在正常血液中被广泛地显示为甲基化或未甲基化，而不在CpG岛（NCGIs）内的CpG位点大部分被甲基化。发现淋巴瘤细胞系中的数千个CpG位点在正常未甲基化的CGI位点获得甲基化，而在正常甲基化的NCGI位点失去甲基化。这些高甲基化的CpG位点位于数百个基因的启动子区域，例如TWIST 2和TLX 3。此外，注释有“同源框”和“DNA结合”特征的基因在CGI中具有高甲基化的CpG位点。全基因组DNA甲基化定量分析是一种敏感的方法，可能适用于癌症以及其他常见疾病的DNA甲基化变化的研究。
DNA methylation is the conversion of cytosine to 5-methylcytosine, leading to changes in the interactions between DNA and proteins. Methylation of cytosine-guanine (CpG) islands (CGIs) is associated with gene expression silencing of the involved promoter. Although studies focussing on global changes or a few single loci in DNA methylation have been performed in dogs with certain diseases, genome-wide analysis of DNA methylation is required to prospectively identify specific regions with DNA methylation change. The hypothesis of this study was that next-generation sequencing with methylation-specific signatures created by sequential digestion of genomic DNA with SmaI and XmaI enzymes can provide quantitative information on methylation levels. Using blood from healthy dogs and cells obtained from canine lymphoma cell lines, approximately 100,000 CpG sites across the dog genome were analysed with the novel method established in this study. CpG sites in CGIs broadly were shown to be either methylated or unmethylated in normal blood, while CpG sites not within CpG islands (NCGIs) were largely methylated. Thousands of CpG sites in lymphoma cell lines were found to gain methylation at normally unmethylated CGI sites and lose methylation at normally methylated NCGI sites. These hypermethylated CpG sites are located at promoter regions of hundreds of genes, such as TWIST2 and TLX3. In addition, genes annotated with ‘Homeobox’ and ‘DNA-binding’ characteristics have hypermethylated CpG sites in CGIs. Genome-wide quantitative DNA methylation analysis is a sensitive method that is likely to be suitable for studies of DNA methylation changes in cancer, as well as other common diseases in dogs.
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