TY - JOUR A1 - Zhao, Lei A1 - Sun, Ming-an A1 - Li, Zejuan A1 - Bai, Xue A1 - Yu, Miao A1 - Wang, Min A1 - Liang, Liji A1 - Shao, Xiaojian A1 - Arnovitz, Stephen A1 - Wang, Qianfei A1 - He, Chuan A1 - Lu, Xuemei A1 - Chen, Jianjun A1 - Xie, Hehuang T1 - The dynamics of DNA methylation fidelity during mouse embryonic stem cell self-renewal and differentiation Y1 - 2014/08/01 JF - Genome Research JO - Genome Research SP - 1296 EP - 1307 DO - 10.1101/gr.163147.113 VL - 24 IS - 8 UR - http://genome.cshlp.org/content/24/8/1296.abstract N2 - 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. ER -