Differential DNA methylation profiles of human B lymphocytes and Epstein-Barr virus-immortalized B lymphocytes
Differential DNA methylation profiles of human B lymphocytes and Epstein-Barr virus-immortalized B lymphocytes
复制标题
人 B 淋巴细胞和 Epstein-Barr 病毒永生化 B 淋巴细胞的差异 DNA 甲基化谱。
DOI：
10.21147/j.issn.1000-9604.2018.01.11
复制
发表时间：
2018-02-01
影响因子：
5.1
通讯作者：
Yang, Wenjun
中科院分区：
文献类型：
--
作者：
Zhang, Chaoting;Zhang, Rui;Yang, Wenjun
目的：本研究旨在全面评估EB病毒（Epstein-Barr virus，EBV）诱导的B细胞全基因组甲基化改变。方法：我们比较了8名受试者的原代B细胞和相应的淋巴母细胞系（LCL）DNA甲基化模式。结果：DNA甲基化分析显示，LCL中有87，732个CpG位点发生了甲基化差异，约占原代B细胞中所有位点的12.41%。高甲基化和低甲基化的CpG位点分别占22.75%和77.25%。CpG岛上的低甲基化位点和高甲基化位点分别为0.8%和4.5%，而海岸（N_海岸和S_海岸）上的低甲基化位点和高甲基化位点分别为8.0%和16.3%。使用DNA甲基化谱的主成分分析，可以准确地预测原代B细胞和LCL。基因本体论（GO）和京都基因与基因组百科全书（KEGG）对不同甲基化基因的分析表明，GO的大部分生物学过程与细胞活化和免疫反应有关，部分GO的富集途径与人类B细胞的活化和恶性转化有关。我们的研究表明，原代B细胞和相应的LCL之间存在全基因组DNA甲基化变异，这可能会对EBV诱导的永生化的甲基化机制产生新的见解。
Objective: This study aimed to comprehensively assess Epstein-Barr virus (EBV)-induced methylation alterations of B cell across whole genome.Methods: We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines (LCLs) from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results: DNA methylation analysis revealed 87,732 differentially methylated CpG sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated CpG sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in CpG islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore (N_shore and S_shore). Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions: Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.