Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG promoter regions in lymphoblastoid cell lines.
Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG promoter regions in lymphoblastoid cell lines.
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DOI：
10.1186/s40246-017-0106-6
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发表时间：
2017-05-12
期刊：
影响因子：
4.5
通讯作者：
Yamamoto K
中科院分区：
文献类型：
--
作者：
Taniguchi I;Iwaya C;Ohnaka K;Shibata H;Yamamoto K
DNA甲基化谱的流行病学研究可能揭示遗传和环境因素导致多因素疾病风险的分子机制。有两种类型的常用DNA生物资源，外周血细胞（PBMC）和EBV转化的淋巴母细胞系（LCL），可用于遗传流行病学研究。因此，扩大我们对LCL和PBMC之间DNA甲基化状态差异的了解，对于使用这些DNA来源阐明多因素疾病的表观遗传风险的人群研究非常重要。我们使用人类甲基化450 K阵列分析了分别从PBMC和LCL获得的192和92个DNA样本的常染色体甲基化状态。在排除SNP相关甲基化位点和低识别位点后，使用以细胞类型、性别和年龄作为自变量的广义线性模型对400，240个位点进行分析。我们发现，与PBMC相比，LCL中大部分位点显示较低的甲基化水平，这与以前的报道一致。我们还发现，显著不同的甲基化位点往往位于CpG岛的外侧，并且位于距离转录起始位点相对较远的区域。此外，我们观察到低CpG启动子区域的位点的甲基化变化是显著的。最后，结果表明，LCL中的年龄和年龄相关的甲基化位点之间的相关性弱于PBMC中的相关性。低CpG密度启动子的高甲基化位点的甲基化水平在LCL中降低，表明位于低CpG密度启动子的甲基化位点可能对LCL中的去甲基化敏感。尽管LCL是由单细胞类型产生的，但在试图阐明表观遗传变化在疾病风险中的作用的表观基因组全分析研究中，LCL可能并不总是来自PBMC的DNA的代表。本文的在线版本（doi：10.1186/s40246-017-0106-6）包含补充材料，可供授权用户使用。
Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases. We analyzed the methylation status of the autosomes for 192 and 92 DNA samples that were obtained from PBCs and LCLs, respectively, using a human methylation 450 K array. After excluding SNP-associated methylation sites and low-call sites, 400,240 sites were subjected to analysis using a generalized linear model with cell type, sex, and age as the independent variables. We found that the large proportion of sites showed lower methylation levels in LCLs compared with PBCs, which is consistent with previous reports. We also found that significantly different methylation sites tend to be located on the outside of the CpG island and in a region relatively far from the transcription start site. Additionally, we observed that the methylation change of the sites in the low-CpG promoter region was remarkable. Finally, it was shown that the correlation between the chronological age and ageing-associated methylation sites in ELOVL2 and FHL2 in the LCLs was weaker than that in the PBCs. The methylation levels of highly methylated sites of the low-CpG-density promoters in PBCs decreased in the LCLs, suggesting that the methylation sites located in low-CpG-density promoters could be sensitive to demethylation in LCLs. Despite being generated from a single cell type, LCLs may not always be a proxy for DNA from PBCs in studies of epigenome-wide analysis attempting to elucidate the role of epigenetic change in disease risks. The online version of this article (doi:10.1186/s40246-017-0106-6) contains supplementary material, which is available to authorized users.