De novo DNA methylation during monkey pre-implantation embryogenesis

Cell Res. 2017 Apr;27(4):526-539. doi: 10.1038/cr.2017.25. Epub 2017 Feb 24.

Abstract

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.

MeSH terms

  • Animals
  • CpG Islands / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Demethylation
  • DNA Methylation / genetics*
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Embryo Implantation / genetics*
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Knockdown Techniques
  • Germ Cells / metabolism
  • Haplorhini
  • Male
  • Mice
  • X Chromosome Inactivation / genetics

Substances

  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A