title: A unique regulatory phase of DNA methylation in the early mammalian embryo.
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.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Smith
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Chan
authors.forename: Tarjei S
authors.initials: TS
authors.lastname: Mikkelsen
authors.forename: Hongcang
authors.initials: H
authors.lastname: Gu
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005306:Fertilization / Q000235:genetics; D016678:Genome / Q000235:genetics; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism; D020079:Terminal Repeat Sequences / Q000235:genetics; D015053:Zygote / Q000378:metabolism