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dc.contributor.authorIvanova, Elena
dc.contributor.authorCanovas, Sebastian
dc.contributor.authorGarcia-Martínez, Soledad
dc.contributor.authorRomar, Raquel
dc.contributor.authorLopes, Jordana S
dc.contributor.authorRizos, Dimitrios
dc.contributor.authorSanchez-Calabuig, Maria J
dc.contributor.authorKrueger, Felix
dc.contributor.authorAndrews, Simon Richard
dc.contributor.authorPerez-Sanz, Fernando
dc.contributor.authorKelsey, Gavin
dc.contributor.authorCoy, Pilar
dc.date.accessioned2020-07-14T23:30:16Z
dc.date.available2020-07-14T23:30:16Z
dc.date.issued2020-05-11
dc.identifier.issn1868-7075
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/307954
dc.description.abstractPreimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8-16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8-16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectGerm Cells
dc.subjectOocytes
dc.subjectBlastocyst
dc.subjectAnimals
dc.subjectCattle
dc.subjectSwine
dc.subjectHumans
dc.subjectMice
dc.subjectSpecies Specificity
dc.subjectDNA Methylation
dc.subjectGene Expression
dc.subjectGenomic Imprinting
dc.subjectPromoter Regions, Genetic
dc.titleDNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2020
prism.publicationNameClin Epigenetics
prism.startingPage64
prism.volume12
dc.identifier.doi10.17863/CAM.55046
dcterms.dateAccepted2020-04-23
rioxxterms.versionofrecord10.1186/s13148-020-00857-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-05-11
dc.contributor.orcidAndrews, Simon Richard [0000-0002-5006-3507]
dc.contributor.orcidKelsey, Gavin [0000-0002-9762-5634]
dc.contributor.orcidCoy, Pilar [0000-0002-3943-1890]
dc.identifier.eissn1868-7083
rioxxterms.typeJournal Article/Review
cam.issuedOnline2020-05-11


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International