甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化

doi:10.3969/j.issn.1004-616x.2019.06.003

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (6): 434-439.doi: 10.3969/j.issn.1004-616x.2019.06.003

甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化

田雪蕾, 封江彬, 田梅, 刘青杰

中国疾病预防控制中心辐射防护与核安全医学所, 中国疾病预防控制中心辐射防护与核应急重点实验室, 北京 100088

收稿日期:2019-04-12 修回日期:2019-10-16 出版日期:2019-11-30 发布日期:2019-12-04
通讯作者: 刘青杰,E-mail:liuqingjie@nirp.chinacdc.cn E-mail:liuqingjie@nirp.chinacdc.cn
作者简介:田雪蕾,E-mail:tianxuelei@nirp.chinacdc.cn。
基金资助:
国家自然科学基金项目（81573081）

Use of a methylation chip to detect DNA methylation in human periphery blood lymphocytes exposed to ionizing radiation

TIAN Xuelei, FENG Jiangbin, TIAN Mei, LIU Qingjie

China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China

Received:2019-04-12 Revised:2019-10-16 Online:2019-11-30 Published:2019-12-04

摘要/Abstract

摘要： 目的：筛选正常人细胞基因组中电离辐射后甲基化水平发生变化的基因，为在其中寻找新型辐射损伤标志物奠定研究基础。方法：⁶⁰Co γ射线照射人外周血全血，照射剂量为0、0.5和2.0 Gy。利用Illumina 450K芯片检测外周血淋巴细胞基因组DNA甲基化水平的变化，筛选甲基化水平差异的基因，利用GO功能富集分析基因的分子功能和参与的生物学途径。结果：0.5和2.0 Gy γ射线照射下人外周血淋巴细胞基因组DNA甲基化水平显著上调的基因有1 311个，显著下调的基因286个。GO功能富集分析表明，按富集度大小排列，差异基因在生物途径水平上排在首位的是“细胞过程”（富集度=5.86），在细胞定位水平上排在首位的是“细胞”（富集度=7.48），在分子功能水平上排在首位的是“结合”（富集度=5.27）。进一步细分后得到差异基因显著富集在与转录调控及转录因子活性相关的功能上，与以往的研究结果认为DNA甲基化参与转录调控和基因表达相一致；甲基化水平差异基因还显著富集在核苷连接（GO：0001882）上，并在其中寻找到与DNA修复相关的基因RAD50、RAD54L和INIP，以及与维持染色体结构稳定相关的基因HIST1H4K、SMC1B。结论：正常人外周血淋巴细胞基因甲基化水平受电离辐射影响，可进一步研究将这些与DNA修复、维持染色体结构稳定相关的基因甲基化水平作为辐射损伤标志物的可行性。

关键词: DNA甲基化, Illumina 450K芯片, GO功能富集分析, 辐射生物标志物, 电离辐射

Abstract: OBJECTIVE: To screen methylated differential genes in normal human periphery blood lymphocytes that were exposed to ⁶⁰Co γ-rays. METHODS: Methylation level of genes were detected by Illumina 450K chip in human periphery blood lymphocytes exposed to 0,0.5 and 2 Gy. The molecular function and bio-pathway of methylated differential genes were analyzed by GO enrichment analysis. RESULTS: There were 1 311 hypermethylation genes and 286 hypomethylation genes both of in the 0.5 Gy and the 2.0 Gy γ irradiation groups. According to the degree of enrichment,our data indicate that the biological process,cell component and molecular function of methylated differential genes were significantly enriched on cell process (enrichment degree=5.86)、cell (enrichment degree=7.48) and binding (enrichment degree=5.27). After further analysis,the results show that methylated differential genes were enriched on terms related to transcription and transcript factor activities which have been identified in other studies. In addition,methylated differential genes also enriched on nucleoside binding (GO:0001882). Some genes related to DNA repair and maintaining chromosome structure were also found such as RAD50,RAD54L,INIP,HIST1H4K and SMC1B. CONCLUSION: Ionizing radiation can change the methylation level of genes in normal human periphery blood lymphocytes. In future studies,genes related to DNA repair and maintainence of chromosome structure will be investigated to determine whether they can be novel radiation damage bio-marker or not.

Key words: DNA methylation, Illumina 450K chip, GO enrichment analysis, radiation bio-marker, ionizing radiation

中图分类号:

Q691.5

田雪蕾, 封江彬, 田梅, 刘青杰. 甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化[J]. 癌变·畸变·突变, 2019, 31(6): 434-439.

TIAN Xuelei, FENG Jiangbin, TIAN Mei, LIU Qingjie. Use of a methylation chip to detect DNA methylation in human periphery blood lymphocytes exposed to ionizing radiation[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(6): 434-439.

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甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化

Use of a methylation chip to detect DNA methylation in human periphery blood lymphocytes exposed to ionizing radiation

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