A unique regulatory phase of DNA methylation in the early mammalian embryo
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Author(s)
Chan, Michelle Mei Wah
Regev, Aviv
Smith, Zachary D.
Gu, Hongcang
Gnirke, Andreas
Meissner, Alexander
Mikkelsen, Tarjei Sigurd, 1978-
Date Issued
March 2012
Journal
Nature
Publisher
Nature Publishing Group
Citation
Smith, Zachary D. et al. “A Unique Regulatory Phase of DNA Methylation in the Early Mammalian Embryo.” Nature 484.7394 (2012): 339–344.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/nature10960
