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dc.contributor.authorNovo, Claraen
dc.contributor.authorTang, Cen
dc.contributor.authorAhmed, Ken
dc.contributor.authorDjuric, Uen
dc.contributor.authorFussner, Een
dc.contributor.authorMullin, NPen
dc.contributor.authorMorgan, NPen
dc.contributor.authorHayre, Jen
dc.contributor.authorSienerth, ARen
dc.contributor.authorElderkin, Sarahen
dc.contributor.authorNishinakamura, Ren
dc.contributor.authorChambers, Ien
dc.contributor.authorEllis, Jen
dc.contributor.authorBazett-Jones, DPen
dc.contributor.authorRugg-Gunn, Peteren
dc.date.accessioned2016-04-12T14:20:34Z
dc.date.available2016-04-12T14:20:34Z
dc.date.issued2016-04-28en
dc.identifier.citationGenes & Development 2016en
dc.identifier.issn0890-9369
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/254925
dc.description.abstractAn open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.
dc.languageENGen
dc.language.isoenen
dc.publisherCold Spring Harbor Laboratory Press
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectStemCellInstituteen
dc.subjectembryonic stem cellsen
dc.subjectheterochromatinen
dc.subjectnuclear organizationen
dc.subjectpluripotencyen
dc.titleThe pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.en
dc.typeArticle
dc.provenanceOA-8192
prism.endingPage1115
prism.publicationDate2016en
prism.publicationNameGenes and Developmenten
prism.startingPage1111
prism.volume30en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderMRC
dc.rioxxterms.projectidWT093736
dc.rioxxterms.projectidM022285
dcterms.dateAccepted2016-03-23en
rioxxterms.versionofrecord10.1101/gad.275685.115en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-04-28en
dc.contributor.orcidNovo, Clara [0000-0003-1435-4136]
dc.contributor.orcidRugg-Gunn, Peter [0000-0002-9601-5949]
dc.identifier.eissn1549-5477
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_PC_12009)
cam.issuedOnline2016-04-28en
cam.orpheus.successThu Jan 30 12:54:31 GMT 2020 - Embargo updated*


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