{"doi":"10.1038/nature10960","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.","journal":"Nature","year":2012,"id":714,"datarank":1.0325193879619639,"base_score":6.883462586413092,"endowment":6.883462586413092,"self_citation_contribution":1.0325193879619639,"citation_network_contribution":0.0,"self_endowment_contribution":1.0325193879619639,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":975,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0773,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2012-03-28","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7052,"name":"Michelle M. Chan","orcid":"0000-0001-9451-9716","position":1,"is_corresponding":false},{"id":7053,"name":"Tarjei S. Mikkelsen","orcid":"0000-0002-8133-3135","position":2,"is_corresponding":false},{"id":7054,"name":"Hongcang Gu","orcid":"0000-0002-1439-7606","position":3,"is_corresponding":false},{"id":7055,"name":"Andreas Gnirke","orcid":"0000-0001-5324-6387","position":4,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":5,"is_corresponding":false},{"id":769,"name":"Alexander Meissner","orcid":"0000-0001-8646-7469","position":6,"is_corresponding":false},{"id":7051,"name":"Zachary D. Smith","orcid":"0000-0002-9283-1957","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}