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dc.contributor.authorPerez-Garcia, Arantxa 
dc.contributor.authorMarina-Zarate, Ester 
dc.contributor.authorÁlvarez-Prado, Ángel Francisco 
dc.contributor.authorLigos, Jose M. 
dc.contributor.authorGaljart, Niels
dc.contributor.authorRamiro, Almudena R 
dc.date.accessioned2017-10-20T10:23:10Z
dc.date.available2017-10-20T10:23:10Z
dc.date.issued2017
dc.identifierISI:000404781100001
dc.identifier.citationNat Commun. 2017; 8:16067
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5106
dc.description.abstractIn germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation.
dc.description.sponsorshipWe thank all members of the B Cell Biology Laboratory, M. Manzanares and C. Badia for helpful discussions; M. Busslinger for kindly providing the AID-CRE<SUP>+/TG</SUP> mice and critical reading of our manuscript; S. Mur for technical support; F. Sanchez-Cabo and M. Gomez for help with RNA-seq and statistical analyses; Genomics and Cellomics Units for technical advise; A. Losada, J. Mendez and V.G. de Yebenes for critical reading of the manuscript. NGS experiments were performed in the Genomics Unit of the CNIC. A. P.-G. was a fellow of the research training programme (FPU-AP2009-1732) funded by the Ministerio de Educacion, Cultura y Deporte; E.M.-Z. is a fellow of the research training programme (FPI) funded by the Ministerio de Economia y Competitividad (BES-2014-069525); A. F. A.-P. and A.R.R. are supported by Centro Nacional de Investigaciones Cardiovaculares (CNIC). This work was funded by the research grant SAF2013-42767-R and SAF2016-75511-R (Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016 Programa Estatal de I+D+i Orientada a los Retos de la Sociedad Retos Investigacion: Proyectos I+D+i 2016, Ministerio de Economia, Industria y Competitividad) and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) and the European Research Council Starting Grant programme (BCLYM-207844) to A.R.R. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject3' REGULATORY REGION
dc.subjectC-MYC GENE
dc.subjectIGH LOCUS
dc.subjectT-CELLS
dc.subjectB-CELLS
dc.subjectCHROMATIN ARCHITECTURE
dc.subjectV(D)J RECOMBINATION
dc.subjectGENOME
dc.subjectEXPRESSION
dc.subjectBLIMP-1
dc.titleCTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28677680
dc.format.volume8
dc.identifier.doi10.1038/ncomms16067
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderCentro Nacional de Investigaciones Cardiovaculares
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderEuropean Research Council Starting Grant programme
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderFundación ProCNIC
dc.contributor.funderSevero Ochoa Center of Excellence (MEIC)
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/ncomms16067
dc.identifier.journalNature Communications
dc.repisalud.orgCNICCNIC::Grupos de investigación::Biología de linfocitos B
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2014-069525es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-42767-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-75511-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU-AP2009-1732es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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