dc.contributor.author | Perez-Garcia, Arantxa | |
dc.contributor.author | Marina-Zarate, Ester | |
dc.contributor.author | Alvarez-Prado, Angel Francisco | |
dc.contributor.author | Ligos, Jose M. | |
dc.contributor.author | Galjart, Niels | |
dc.contributor.author | Ramiro, Almudena R | |
dc.date.accessioned | 2017-10-20T10:23:10Z | |
dc.date.available | 2017-10-20T10:23:10Z | |
dc.date.issued | 2017 | |
dc.identifier | ISI:000404781100001 | |
dc.identifier.citation | Nat Commun. 2017; 8:16067 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5106 | |
dc.description.abstract | In 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.sponsorship | We 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.iso | eng | |
dc.publisher | Nature Publishing Group | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | 3' REGULATORY REGION | |
dc.subject | C-MYC GENE | |
dc.subject | IGH LOCUS | |
dc.subject | T-CELLS | |
dc.subject | B-CELLS | |
dc.subject | CHROMATIN ARCHITECTURE | |
dc.subject | V(D)J RECOMBINATION | |
dc.subject | GENOME | |
dc.subject | EXPRESSION | |
dc.subject | BLIMP-1 | |
dc.title | CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28677680 | |
dc.format.volume | 8 | |
dc.identifier.doi | 10.1038/ncomms16067 | |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Centro Nacional de Investigaciones Cardiovasculares Carlos III (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1038/ncomms16067 | |
dc.identifier.journal | Nature Communications | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Biología de linfocitos B | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BES-2014-069525 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-42767-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-75511-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FPU-AP2009-1732 | es_ES |
dc.rights.accessRights | open access | es_ES |