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dc.contributor.authorScarola, Michele
dc.contributor.authorComisso, Elisa
dc.contributor.authorPascolo, Rhena
dc.contributor.authorChiaradia, Riccardo
dc.contributor.authorMarion, RM 
dc.contributor.authorSchneider, Claudio
dc.contributor.authorBlasco, MA 
dc.contributor.authorSchoeftner, Stefan
dc.contributor.authorBenetti, Roberta
dc.date.accessioned2020-05-08T17:30:56Z
dc.date.available2020-05-08T17:30:56Z
dc.date.issued2015-07-09
dc.identifier.citationNat Commun. 2015;6:763es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10007
dc.description.abstractPseudogene-derived, long non-coding RNAs (lncRNAs) act as epigenetic regulators of gene expression. Here we present a panel of new mouse Oct4 pseudogenes and demonstrate that the X-linked Oct4 pseudogene Oct4P4 critically impacts mouse embryonic stem cells (mESCs) self-renewal. Sense Oct4P4 transcription produces a spliced, nuclear-restricted lncRNA that is efficiently upregulated during mESC differentiation. Oct4P4 lncRNA forms a complex with the SUV39H1 HMTase to direct the imposition of H3K9me3 and HP1α to the promoter of the ancestral Oct4 gene, located on chromosome 17, leading to gene silencing and reduced mESC self-renewal. Targeting Oct4P4 expression in primary mouse embryonic fibroblasts causes the re-acquisition of self-renewing features of mESC. We demonstrate that Oct4P4 lncRNA plays an important role in inducing and maintaining silencing of the ancestral Oct4 gene in differentiating mESCs. Our data introduces a sense pseudogene-lncRNA-based mechanism of epigenetic gene regulation that controls the cross-talk between pseudogenes and their ancestral genes.es_ES
dc.description.sponsorshipWe thank Alessandro Marcello (ICGEB Trieste, Italy) for providing the basic vectors for the MS2 tethering model. M.S. is supported by a AIRC post-doctoral fellowship; E.C. is enroled in the PhD program for Molecular Medicine at the University of Trieste. This work was supported by an Italian Association for Cancer Research (AIRC) grant Rif 42/08, 6352 to R.B., an Italian Association for Cancer Research (AIRC) grant cod. 10299 and a Fondazione Veronesi grant to S.S. and by a grant from the Italian Ministry of Education, Universities and Research (MIUR) CTN01_00177_817708 to C.S.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshCell Line es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Self Renewal es_ES
dc.subject.meshChromatin Immunoprecipitation es_ES
dc.subject.meshChromosomal Proteins, Non-Histone es_ES
dc.subject.meshEpigenesis, Genetic es_ES
dc.subject.meshHistones es_ES
dc.subject.meshImmunoprecipitation es_ES
dc.subject.meshMethyltransferases es_ES
dc.subject.meshMice es_ES
dc.subject.meshMouse Embryonic Stem Cells es_ES
dc.subject.meshNIH 3T3 Cells es_ES
dc.subject.meshOctamer Transcription Factor-3 es_ES
dc.subject.meshPseudogenes es_ES
dc.subject.meshRNA, Long Noncoding es_ES
dc.subject.meshRepressor Proteins es_ES
dc.subject.meshGene Expression Regulation, Developmental es_ES
dc.titleEpigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNAes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID26158551es_ES
dc.format.volume6es_ES
dc.format.number1es_ES
dc.format.page7631es_ES
dc.identifier.doi10.1038/ncomms8631es_ES
dc.contributor.funderItalian Association for Cancer Research 
dc.contributor.funderFondazione Umberto Veronesi 
dc.contributor.funderMinistero dell Istruzione, dell Universita e della Ricerca (Italia) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/ncomms8631.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Telómeros y Telomerasaes_ES
dc.rights.accessRightsopen accesses_ES


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