西亚试剂：unique regulatory phase of DNA methylation in the early

A unique regulatory phase of DNA methylation in the early mammalian embryo

Zachary D. Smith, Michelle M. Chan, Tarjei S. Mikkelsen, Hongcang Gu, Andreas Gnirke, Aviv Regev & Alexander Meissner

DNA methylation is highly dynamic during mammalian embryogenesis.It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage.However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation.We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm.Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)—including many CpG island promoters—that are maintained in the early embryo but are lost upon specification and absent from somatic cells.In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage.Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.