Volume 27, No 4, Apr 2017

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 27 Issue 4, April 2017: 526-539   |  Open Access

ORIGINAL ARTICLES

De novo DNA methylation during monkey pre-implantation embryogenesis

Fei Gao^2,*, Yuyu Niu^1,3,*, Yi Eve Sun^1,4,5,*, Hanlin Lu^2,*, Yongchang Chen^1,3,*, Siguang Li^4,*, Yu Kang^1,3, Yuping Luo⁴, Chenyang Si^1,3, Juehua Yu⁵, Chang Li^1,3, Nianqin Sun^1,3, Wei Si^1,3, Hong Wang^1,3, Weizhi Ji^1,3 and Tao Tan^1,3

¹Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
²Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong 518120, China
³National Engineering Research Center of Biomedicine and Animal Science, Kunming, Yunnan 650500, China
⁴Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, China
⁵Department of Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095, USA Correspondence: Tao Tan, E-mail: tant@lpbr.cn; Weizhi Ji, E-mail: wji@lpbr.cn

Critical epigenetic regulation of primate embryogenesis entails DNA methylome changes. Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. We show that upon fertilization, both paternal and maternal genomes undergo active DNA demethylation, and genome-wide de novo DNA methylation is also initiated in the same period. By the 8-cell stage, remethylation becomes more pronounced than demethylation, resulting in an increase in global DNA methylation. Promoters of genes associated with oxidative phosphorylation are preferentially remethylated at the 8-cell stage, suggesting that this mode of energy metabolism may not be favored. Unlike in rodents, X chromosome inactivation is not observed during monkey pre-implantation development. Our study provides the first comprehensive illustration of the 'wax and wane' phases of DNA methylation dynamics. Most importantly, our DNA methyltransferase loss-of-function analysis indicates that DNA methylation influences early monkey embryogenesis.

10.1038/cr.2017.25

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