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dc.contributor.authorRichart, Laia
dc.contributor.authorLapi, Eleonora
dc.contributor.authorPancaldi, Vera
dc.contributor.authorCuenca-Ardura, Mirabai
dc.contributor.authorPau, Enrique Carrillo-de-Santa
dc.contributor.authorMadrid-Mencía, Miguel
dc.contributor.authorNeyret-Kahn, Hélène
dc.contributor.authorRadvanyi, François
dc.contributor.authorRodríguez, Juan Antonio
dc.contributor.authorCuartero, Yasmina
dc.contributor.authorSerra, François
dc.contributor.authorLe Dily, François
dc.contributor.authorValencia, Alfonso 
dc.contributor.authorMarti-Renom, Marc A
dc.contributor.authorReal Arribas, Francisco 
dc.date.accessioned2022-03-04T10:39:21Z
dc.date.available2022-03-04T10:39:21Z
dc.date.issued2021-11-08
dc.identifier.citationNucleic Acids Res . 2021 ;49(19):11005-11021.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13723
dc.description.abstractCohesin exists in two variants containing STAG1 or STAG2. STAG2 is one of the most mutated genes in cancer and a major bladder tumor suppressor. Little is known about how its inactivation contributes to tumorigenesis. Here, we analyze the genomic distribution of STAG1 and STAG2 and perform STAG2 loss-of-function experiments using RT112 bladder cancer cells; we then analyze the genomic effects by integrating gene expression and chromatin interaction data. Functional compartmentalization exists between the cohesin complexes: cohesin-STAG2 displays a distinctive genomic distribution and mediates short and mid-ranged interactions that engage genes at higher frequency than those established by cohesin-STAG1. STAG2 knockdown results in down-regulation of the luminal urothelial signature and up-regulation of the basal transcriptional program, mirroring differences between STAG2-high and STAG2-low human bladder tumors. This is accompanied by rewiring of DNA contacts within topological domains, while compartments and domain boundaries remain refractive. Contacts lost upon depletion of STAG2 are assortative, preferentially occur within silent chromatin domains, and are associated with de-repression of lineage-specifying genes. Our findings indicate that STAG2 participates in the DNA looping that keeps the basal transcriptional program silent and thus sustains the luminal program. This mechanism may contribute to the tumor suppressor function of STAG2 in the urothelium.es_ES
dc.description.sponsorshipFundacion Cientifica de la Asociacion Espanola Contra el Cancer (to F.X.R., E.L., in part); V.P. is supported by INSERM, the Fondation Toulouse Cancer Sante and Pierre Fabre Research Institute as part of the Chair of Bioinformatics in Oncology of the CRCT; Bioinfo4women programme at the Barcelona Supercomputing Center; European Union's H2020 Framework Programme through the ERC [609989 to M.A.M.-R., in part]; Spanish Ministerio de Ciencia, Innovaci ' on y Universidades [BFU2017-85926P to M.A.M.-R.]; C.N.I.O. is supported by Ministerio de Ciencia, Innovacion y Universidades as a Centro de Excelencia Severo Ochoa [SEV-2015-0510]; C.R.G. acknowledges support from 'Centro de Excelencia Severo Ochoa 2013-2017' [SEV-2012-0208]; Spanish ministry of Science and Innovation to the EMBL partnership and the CERCA Programme/Generalitat de Catalunya (to C.R.G.); C.R.G. also acknowledges support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, the Generalitat de Catalunya through Departament de Salut and Departament d'Empresa i Coneixement; Spanish Ministry of Science and Innovation with funds from the European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth Operating Program (to C.N.A.G.). Funding for open access charge: Own funds.es_ES
dc.language.isoenges_ES
dc.publisherOxford University Press es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCOHESIN COMPLEXes_ES
dc.subjectMUTATIONSes_ES
dc.subjectGENESes_ES
dc.subjectREVEALSes_ES
dc.subjectINACTIVATIONes_ES
dc.subjectPRINCIPLESes_ES
dc.subjectCOMPONENTSes_ES
dc.subjectANEUPLOIDYes_ES
dc.subjectELEMENTSes_ES
dc.subjectDOMAINes_ES
dc.subject.meshLoss of Function Mutation es_ES
dc.subject.meshTranscription, Genetic es_ES
dc.subject.meshBase Sequence es_ES
dc.subject.meshCell Cycle Proteins es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshChromatin es_ES
dc.subject.meshChromosomal Proteins, Non-Histone es_ES
dc.subject.meshDNA, Neoplasm es_ES
dc.subject.meshGene Expression Profiling es_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshGene Ontology es_ES
dc.subject.meshHEK293 Cells es_ES
dc.subject.meshHistones es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMolecular Sequence Annotation es_ES
dc.subject.meshNuclear Proteins es_ES
dc.subject.meshRNA, Small Interfering es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshUrinary Bladder Neoplasms es_ES
dc.titleSTAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID34648034es_ES
dc.format.volume49es_ES
dc.format.number19es_ES
dc.format.page11005-11021es_ES
dc.identifier.doi10.1093/nar/gkab864es_ES
dc.contributor.funderAsociación Española Contra el Cáncer es_ES
dc.contributor.funderInstitut National de la Santé et de la Recherche Médicale (Francia) es_ES
dc.contributor.funderFondation Toulouse Cancer Santees_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España) es_ES
dc.contributor.funderInstitució Catalana de Recerca i Estudis Avançats es_ES
dc.contributor.funderGovernment of Catalonia (España) es_ES
dc.contributor.funderUnión Europea. Comisión Europea es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1362-4962es_ES
dc.relation.publisherversionhttps://doi.org/10.1093/nar/gkab864.es_ES
dc.identifier.journalNucleic acids researches_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Carcinogénesis Epiteliales_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/BFU2017-85926Pes_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/SEV-2015-0510es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/SEV-2012-0208es_ES


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