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dc.contributor.authorLópez-Farfán, Diana
dc.contributor.authorBart, Jean Mathieu 
dc.contributor.authorRojas-Barros, Domingo I
dc.contributor.authorNavarro, Miguel
dc.date.accessioned2018-12-07T13:01:10Z
dc.date.available2018-12-07T13:01:10Z
dc.date.issued2014-12-04
dc.identifier.citationPLoS Pathog. 2014 Dec 4;10(12):e1004545.es_ES
dc.identifier.issn1553-7374es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6787
dc.description.abstractBloodstream form trypanosomes avoid the host immune response by switching the expression of their surface proteins between Variant Surface Glycoproteins (VSG), only one of which is expressed at any given time. Monoallelic transcription of the telomeric VSG Expression Site (ES) by RNA polymerase I (RNA pol I) localizes to a unique nuclear body named the ESB. Most work has focused on silencing mechanisms of inactive VSG-ESs, but the mechanisms involved in transcriptional activation of a single VSG-ES remain largely unknown. Here, we identify a highly SUMOylated focus (HSF) in the nucleus of the bloodstream form that partially colocalizes with the ESB and the active VSG-ES locus. SUMOylation of chromatin-associated proteins was enriched along the active VSG-ES transcriptional unit, in contrast to silent VSG-ES or rDNA, suggesting that it is a distinct feature of VSG-ES monoallelic expression. In addition, sequences upstream of the active VSG-ES promoter were highly enriched in SUMOylated proteins. We identified TbSIZ1/PIAS1 as the SUMO E3 ligase responsible for SUMOylation in the active VSG-ES chromatin. Reduction of SUMO-conjugated proteins by TbSIZ1 knockdown decreased the recruitment of RNA pol I to the VSG-ES and the VSG-ES-derived transcripts. Furthermore, cells depleted of SUMO conjugated proteins by TbUBC9 and TbSUMO knockdown confirmed the positive function of SUMO for VSG-ES expression. In addition, the largest subunit of RNA pol I TbRPA1 was SUMOylated in a TbSIZ-dependent manner. Our results show a positive mechanism associated with active VSG-ES expression via post-translational modification, and indicate that chromatin SUMOylation plays an important role in the regulation of VSG-ES. Thus, protein SUMOylation is linked to active gene expression in this protozoan parasite that diverged early in evolution.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministerio de Ciencia e Innovación, (SAF2012-40029), Junta de Andalucia (CTS-5841) and Instituto de Salud Carlos III, RICET (RICET RD12/0018/0015) grants. JMB is supported by a Miguel Servet fellowship (CP09/00300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshCell Nucleolus es_ES
dc.subject.meshChromatin es_ES
dc.subject.meshGene Expression Regulation es_ES
dc.subject.meshGlycoproteins es_ES
dc.subject.meshProtein Inhibitors of Activated STAT es_ES
dc.subject.meshProtein Processing, Post-Translational es_ES
dc.subject.meshProtozoan Proteins es_ES
dc.subject.meshSumoylation es_ES
dc.subject.meshTrypanosoma brucei brucei es_ES
dc.subject.meshUbiquitin-Protein Ligases es_ES
dc.titleSUMOylation by the E3 ligase TbSIZ1/PIAS1 positively regulates VSG expression in Trypanosoma bruceies_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID25474309es_ES
dc.format.volume10es_ES
dc.format.number12es_ES
dc.format.pagee1004545es_ES
dc.identifier.doi10.1371/journal.ppat.1004545es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderRegional Government of Andalusia (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1553-7374es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.ppat.1004545es_ES
dc.identifier.journalPLoS pathogenses_ES
dc.repisalud.centroISCIII::Centro Nacional de Medicina Tropicales_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2012-40029es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional