GSE121758
Methylome Dynamics of Bovine Gametes and In Vivo Early Embryos
Dynamic changes in DNA methylation are crucial in the epigenetic regulation of mammalian embryogenesis. Global DNA methylation studies in the bovine, however, remain mostly at the immunostaining level. We adopted the single-cell whole genome bisulfite sequencing (scWGBS) method to characterize stage-specific genome-wide DNA methylation in bovine sperm, individual oocytes derived in vivo and in vitro, as well as in vivo developed embryos at the 2-, 4-, 8- and 16-cell stages. This method allowed us to theoretically cover all CpG sites in the genome using single oocytes or embryos. We found that the major wave of genome-wide DNA demethylation was complete at the 8-cell stage when de novo methylation became prominent. Sperm and oocytes were differentially methylated in numerous regions (DMRs) which were enriched in intergenic regions, indicating these noncoding regions play important roles in gamete specification. DMRs were also identified between in vivo and in vitro matured oocytes. Moreover, X chromosome methylation followed the global dynamic patterns. Virtually no (less than 1.5%) DNA methylation was found in mitochondrial DNA. Finally, using our RNA-seq data generated from the same developmental stages, we revealed an inverse correlation between gene expression and promoter methylation. Our study provides the first fully comprehensive analysis of the global dynamics of DNA methylation in bovine gametes and single early embryos using scWGBS. These data provide insights into the critical features of the methylome of bovine embryos, and serve as an important reference for embryos produced by assisted reproduction, such as in vitro fertilization and cloning, and a model for human early embryo epigenetic regulation. Overall design: Whole genome bisulfite sequencing was used to determined genome-scale DNA methylation patterns of bovine sperm and individual in vivo developed oocytes and preimplantation embryos.