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Nature DOI:10.1038/nature10960

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

Publication TypeJournal Article
Year of Publication2012
AuthorsSmith, ZD, Chan, MM, Mikkelsen, TS, Gu, H, Gnirke, A, Regev, A, Meissner, A
JournalNature
Volume484
Issue7394
Pages339-44
Date Published2012 Mar 28
ISSN1476-4687
KeywordsAnimals, CpG Islands, DNA Methylation, Embryo, Mammalian, Embryonic Development, Female, Fertilization, Genome, Long Interspersed Nucleotide Elements, Male, Mice, Oocytes, Spermatozoa, Terminal Repeat Sequences, Zygote
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.

URLhttp://dx.doi.org/10.1038/nature10960
DOI10.1038/nature10960
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22456710?dopt=Abstract

Alternate JournalNature
PubMed ID22456710
PubMed Central IDPMC3331945
Grant ListP01 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