Zhao Lei, Sun Ming-An, Li Zejuan, Bai Xue, Yu Miao, Wang Min, Liang Liji, Shao Xiaojian, Arnovitz Stephen, Wang Qianfei, He Chuan, Lu Xuemei, Chen Jianjun, Xie Hehuang
Laboratory of Genome Variation and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;
Epigenomics and Computational Biology Lab, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia 24060, USA;
Genome Res. 2014 Aug;24(8):1296-307. doi: 10.1101/gr.163147.113. Epub 2014 May 16.
The faithful transmission of DNA methylation patterns through cell divisions is essential for the daughter cells to retain a proper cell identity. To achieve a comprehensive assessment of methylation fidelity, we implemented a genome-scale hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously. We show here that methylation fidelity increases globally during differentiation of mouse embryonic stem cells (mESCs), and is particularly high in the promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcription factors. The majority of intermediately (40%-60%) methylated CpG dinucleotides are hemi-methylated and have low methylation fidelity, particularly in the differentiating mESCs. While 5-hmC and 5-mC tend to coexist, there is no significant correlation between 5-hmC levels and methylation fidelity. Our findings may shed new light on our understanding of the origins of methylation variations and the mechanisms underlying DNA methylation transmission.
DNA甲基化模式在细胞分裂过程中的忠实传递对于子细胞保持适当的细胞身份至关重要。为了全面评估甲基化保真度，我们实施了一种全基因组规模的发夹亚硫酸氢盐测序方法，以同时生成DNA双链的甲基化数据。我们在此表明，在小鼠胚胎干细胞（mESC）分化过程中，甲基化保真度在整体上有所增加，并且在活跃表达基因的启动子区域特别高，且与活跃的组蛋白修饰标记以及转录因子的结合呈正相关。大多数中等程度（40%-60%）甲基化的CpG二核苷酸是半甲基化的，并且甲基化保真度较低，尤其是在分化的mESC中。虽然5-羟甲基胞嘧啶（5-hmC）和5-甲基胞嘧啶（5-mC）倾向于共存，但5-hmC水平与甲基化保真度之间没有显著相关性。我们的发现可能为我们理解甲基化变异的起源以及DNA甲基化传递的潜在机制提供新的线索。
