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dc.contributor.authorHörmanseder, Een
dc.contributor.authorSimeone, Angelaen
dc.contributor.authorAllen, GEen
dc.contributor.authorBradshaw, Charlesen
dc.contributor.authorFiglmüller, Men
dc.contributor.authorGurdon, Johnen
dc.contributor.authorJullien, Jeromeen
dc.date.accessioned2017-05-25T17:40:12Z
dc.date.available2017-05-25T17:40:12Z
dc.date.issued2017-03-30en
dc.identifier.issn1934-5909
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264440
dc.description.abstractVertebrate eggs can induce the nuclear reprogramming of somatic cells to enable production of cloned animals. Nuclear reprogramming is relatively inefficient, and the development of the resultant embryos is frequently compromised, in part due to the inappropriate expression of genes previously active in the donor nucleus. Here, we identify H3K4 methylation as a major epigenetic roadblock that limits transcriptional reprogramming and efficient nuclear transfer (NT). Widespread expression of donor-cell-specific genes was observed in inappropriate cell types in NT embryos, limiting their developmental capacity. The expression of these genes in reprogrammed embryos arises from epigenetic memories of a previously active transcriptional state in donor cells that is characterized by high H3K4 methylation. Reducing H3K4 methylation had little effect on gene expression in donor cells, but it substantially improved transcriptional reprogramming and development of NT embryos. These results show that H3K4 methylation imposes a barrier to efficient nuclear reprogramming and suggest approaches for improving reprogramming strategies.
dc.description.sponsorshipThis work was funded by the Molecular Research Council ( MR/P000479/1 ), the Wellcome Trust ( 101050/Z/13/Z and 092096/Z/10/Z ), and Cancer Research UK ( C6946/A14492 ). E.H. was a recipient of a long-term fellowship from the European Molecular Biology Organization (EMBO) and Isaac Newton Trust funding.
dc.languageengen
dc.language.isoenen
dc.publisherElsevier (Cell Press)
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectnuclear transferen
dc.subjectreprogrammingen
dc.subjectepigenetic memoryen
dc.subjectH3K4me3en
dc.subjectKdm5ben
dc.subjectendodermen
dc.subjectcell-fate stabilityen
dc.titleH3K4 Methylation-Dependent Memory of Somatic Cell Identity Inhibits Reprogramming and Development of Nuclear Transfer Embryosen
dc.typeArticle
prism.publicationDate2017en
prism.publicationNameCell Stem Cellen
dc.identifier.doi10.17863/CAM.9918
dcterms.dateAccepted2017-03-07en
rioxxterms.versionofrecord10.1016/j.stem.2017.03.003en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-03-30en
dc.contributor.orcidBradshaw, Charles [0000-0002-3528-458X]
dc.contributor.orcidGurdon, John [0000-0002-5621-3799]
dc.contributor.orcidJullien, Jerome [0000-0002-7868-0021]
dc.identifier.eissn1875-9777
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/P000479/1)
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idMRC (G1001690)
pubs.funder-project-idMRC (MR/K011022/1)
pubs.funder-project-idWellcome Trust (101050/Z/13/Z)
pubs.funder-project-idCancer Research UK (A14492)


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