A unique regulatory phase of DNA methylation in the early mammalian embryo.
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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. |
Year of Publication | 2012
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Journal | Nature
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Volume | 484
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Issue | 7394
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Pages | 339-44
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Date Published | 2012 Mar 28
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ISSN | 1476-4687
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URL | |
DOI | 10.1038/nature10960
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PubMed ID | 22456710
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PubMed Central ID | PMC3331945
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Grant list | P01 GM099117 / GM / NIGMS NIH HHS / United States
U01ES017155 / ES / NIEHS NIH HHS / United States
RC1 AA019317 / AA / NIAAA NIH HHS / United States
5DP1OD003958 / OD / NIH HHS / United States
DP1 CA174427 / CA / NCI NIH HHS / United States
P50 HG006193-01 / HG / NHGRI NIH HHS / United States
P01GM099117 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
DP1 OD003958-04 / OD / NIH HHS / United States
1P50HG006193-01 / HG / NHGRI NIH HHS / United States
5RC1AA019317 / AA / NIAAA NIH HHS / United States
U01 ES017155 / ES / NIEHS NIH HHS / United States
DP1 OD003958 / OD / NIH HHS / United States
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