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dc.contributor.authorRodriguez-Cortez, Virginia C.
dc.contributor.authorMartinez-Redondo, Paloma
dc.contributor.authorCatala-Moll, Francesc
dc.contributor.authorRodriguez-Ubreva, Javier
dc.contributor.authorGarcia-Gomez, Antonio
dc.contributor.authorPoorani-Subramani, Ganesh
dc.contributor.authorCiudad, Laura
dc.contributor.authorHernando, Henar
dc.contributor.authorPerez-Garcia, Arantxa 
dc.contributor.authorCompany, Carlos
dc.contributor.authorUrquiza, Jose M.
dc.contributor.authorRamiro, Almudena R 
dc.contributor.authorDi Noia, Javier M.
dc.contributor.authorVaquero, Alejandro
dc.contributor.authorBallestar, Esteban
dc.date.accessioned2017-10-20T10:23:09Z
dc.date.available2017-10-20T10:23:09Z
dc.date.issued2017
dc.identifierISI:000407180400024
dc.identifier.citationSci Rep. 2017; 7(1):7594
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5101
dc.description.abstractActivation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3. In 293F cells, we demonstrate interaction between co-transfected AID and the three SUV4-20 histone H4K20 methyltransferases, and that SUV4-20H1.2, bound to the IgH switch (S) mu site, is replaced by SUV4-20H2 upon AID binding. Analysis of HIGM2 mutants shows that the AID truncated form W68X is impaired to interact with SUV4-20H1.2 and SUV4-20H2 and is unable to bind and target H4K20me3 to the Smu site. We finally show in mouse primary B cells undergoing class-switch recombination (CSR) that AID deficiency associates with decreased H4K20me3 levels at the Smu site. Our results provide a novel link between SUV4-20 enzymes and CSR and offer a new aspect of the interplay between AID and histone modifications in setting the epigenetic status of CSR sites.
dc.description.sponsorshipThis work was supported by grant SAF2014-55942-R from the Instituto de Salud Carlos III, organisms ascribed to the Ministerio de Economia y Competitividad and cofunded by FEDER funds/European Regional Development Fund (ERDF) - a way to build Europe, and the EU FP7 306000 STATegra project. JMDN is supported by a Canada Research Chair tier II. Work by JMDN and SPG was supported by the Canadian Institutes of Health Research, MOP 125991.
dc.language.isoeng
dc.publisherNature Publishing Group 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectDOUBLE-STRAND BREAKS
dc.subjectSOMATIC HYPERMUTATION
dc.subjectSUPER-ENHANCERS
dc.subjectRECRUIT AID
dc.subjectB-CELLS
dc.subjectDNA
dc.subjectMETHYLATION
dc.subjectREGIONS
dc.subjectDEMETHYLATION
dc.subjectREPAIR
dc.titleActivation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28790320
dc.format.volume7
dc.identifier.doi10.1038/s41598-017-07380-9
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderCanada Research Chairs 
dc.contributor.funderCanadian Institutes of Health Research 
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-017-07380-9
dc.identifier.journalScientific Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Biología de linfocitos B
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-55942-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/306000es_ES
dc.rights.accessRightsopen accesses_ES


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