A unique regulatory phase of DNA methylation in the early mammalian embryo
Author(s)Chan, Michelle Mei Wah; Regev, Aviv; Smith, Zachary D.; Mikkelsen, Tarjei Sigurd; Gu, Hongcang; Gnirke, Andreas; Meissner, Alexander; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology
Nature Publishing Group
Smith, Zachary D. et al. “A Unique Regulatory Phase of DNA Methylation in the Early Mammalian Embryo.” Nature 484.7394 (2012): 339–344.
Author's final manuscript