Publication Date:
2012-03-30
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331945/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331945/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Zachary D -- Chan, Michelle M -- Mikkelsen, Tarjei S -- Gu, Hongcang -- Gnirke, Andreas -- Regev, Aviv -- Meissner, Alexander -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- 5DP1OD003958/OD/NIH HHS/ -- 5RC1AA019317/AA/NIAAA NIH HHS/ -- DP1 CA174427/CA/NCI NIH HHS/ -- DP1 OD003958/OD/NIH HHS/ -- DP1 OD003958-04/OD/NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- P50 HG006193-01/HG/NHGRI NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 28;484(7394):339-44. doi: 10.1038/nature10960.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22456710" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
CpG Islands/genetics
;
*DNA Methylation/genetics
;
Embryo, Mammalian/*embryology/*metabolism
;
Embryonic Development/*genetics
;
Female
;
Fertilization/genetics
;
Genome/genetics
;
Long Interspersed Nucleotide Elements/genetics
;
Male
;
Mice
;
Oocytes/metabolism
;
Spermatozoa/metabolism
;
Terminal Repeat Sequences/genetics
;
Zygote/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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