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 and Alexander Meissner ()
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Zachary D. Smith: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Michelle M. Chan: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Tarjei S. Mikkelsen: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Hongcang Gu: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Andreas Gnirke: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Aviv Regev: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Alexander Meissner: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA

Nature, 2012, vol. 484, issue 7394, 339-344

Abstract: 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.

Date: 2012
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DOI: 10.1038/nature10960

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