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dc.contributor.authorSmith, Austinen
dc.contributor.authorNichols, Jenniferen
dc.date.accessioned2017-08-02T15:08:21Z
dc.date.available2017-08-02T15:08:21Z
dc.date.issued2017-08-18en
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265860
dc.description.abstractExecution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) $\textit{linc1281}$, hereafter $\textit{Ephemeron}$ ($\textit{Eprn}$), that modulates the dynamics of exit from naïve pluripotency. $\textit{Eprn}$ deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of $\textit{Eprn}$, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of $\textit{Eprn}$ or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. $\textit{Eprn}$ illustrates how lncRNAs may introduce species-specific network modulations.
dc.description.sponsorshipAS is supported by Medical Research Council (G1100526/1), Biotechnology and Biological Sciences Research Council (BB/M004023/1), European Commission (HEALTH-F4-2007-200720 EUROSYSTEM), and Wellcome Trust (091484/Z/ 10/Z). LH is supported by National Cancer Institute (R01 CA139067, 1R21CA175560-01) and California Institute of Regenerative Medicine (RN2-00923-1), American Cancer Society (123339-RSG-12- 265-01-RMC), Tobacco-related Disease Research Program (21RT-0133). DLS is supported by NIGMS 42694 and NCI 5PO1CA013106-Project 3. TK is supported by programme grants from Cancer Research UK (C6/A18796) and European Research Council CRIPTON Grant (268569) and core grants from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492). The Cambridge Stem Cell Institute receives core funding from the Wellcome Trust and the Medical Research Council. MAL was a Siebel postdoctoral fellow at the University of California, Berkeley and a Sir Henry Wellcome postdoctoral fellow (096125/Z/11/Z). AS is a Medical Research Council Professor.
dc.language.isoenen
dc.publishereLife Sciences Publications Ltd
dc.rightsAttribution 4.0 Internationalen
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.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleA lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylationen
dc.typeArticle
prism.numbere23468en
prism.publicationDate2017en
prism.publicationNameeLifeen
prism.volume6en
dc.identifier.doi10.17863/CAM.12233
dcterms.dateAccepted2017-07-25en
rioxxterms.versionofrecord10.7554/eLife.23468en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-08-18en
dc.contributor.orcidSmith, Austin [0000-0002-3029-4682]
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idRoyal Society (nf110751)
pubs.funder-project-idEuropean Research Council (268569)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idBBSRC (BB/M004023/1)
pubs.funder-project-idWellcome Trust (096125/Z/11/Z)
pubs.funder-project-idWellcome Trust (091484/Z/10/Z)
pubs.funder-project-idCancer Research UK (A18796)
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idCancer Research UK (A14492)
cam.issuedOnline2017-08-18en
cam.orpheus.successThu Jan 30 13:00:10 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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