DNA methylomes of the bovine gametes and in vivo preimplantation embryos

DNA methylation is an important epigenetic modification that undergoes dynamic changes in mammalian embryogenesis, during which both parental genomes are reprogrammed. Despite the many immunostaining studies that have assessed global methylation, the gene-specific DNA methylation patterns in bovine preimplantation embryos are unknown. Using reduced representation bisulfite sequencing, we determined genome-scale DNA methylation patterns of bovine sperm and individual in vivo developed oocytes and preimplantation embryos. We show that: 1) the major wave of genome-wide demethylation was completed by the 8-cell stage; 2) promoter methylation was significantly and inversely correlated with gene expression at the 8-cell and blastocyst stages; 3) sperm and oocytes have numerous differentially methylated regions (DMRs) - DMRs specific for sperm were strongly enriched in long terminal repeats (LTRs) and rapidly lost methylation in embryos, while the oocyte-specific DMRs were more frequently localized in exons and CpG islands (CGIs) and demethylated gradually across cleavage stages; 4) a unique set of DMRs were found between in vivo and in vitro matured oocytes; and 5) differential methylation between bovine gametes was confirmed in some but not all known imprinted genes. Our data provide insights into deciphering the complex epigenetic reprogramming of bovine early embryos and will serve as an important model for investigating human development and the evolutionary and regulatory roles of DNA methylation. Overall design: Reduced representation bisulfite sequencing was used to determined genome-scale DNA methylation patterns of bovine sperm and individual in vivo developed oocytes and preimplantation embryos.