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dc.rights.licenseopenen_US
dc.contributor.authorALARCON, Valentina
dc.contributor.authorHERNANDEZ, Sergio
dc.contributor.authorRUBIO, Lorena
dc.contributor.authorALVAREZ, Francisca
dc.contributor.authorFLORES, Yvo
dc.contributor.authorVARAS-GODOY, Manuel
dc.contributor.authorDE FERRARI, Giancarlo V
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorKANN, Michael
dc.contributor.authorVILLANUEVA, Rodrigo A
dc.contributor.authorLOYOLA, Alejandra
dc.date.accessioned2023-11-20T16:02:51Z
dc.date.available2023-11-20T16:02:51Z
dc.date.issued2016-05-13
dc.identifier.issn2045-2322en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184917
dc.description.abstractEnWith about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enAcetylation
dc.subject.enCell Line
dc.subject.enChromatin
dc.subject.enGene Expression Regulation
dc.subject.enViral
dc.subject.enHep G2 Cells
dc.subject.enHepatitis B
dc.subject.enHepatitis B virus
dc.subject.enHistone Demethylases
dc.subject.enHistone-Lysine N-Methyltransferase
dc.subject.enHistones
dc.subject.enHumans
dc.subject.enMethylation
dc.subject.enPromoter Regions
dc.subject.enGenetic
dc.subject.enTrans-Activators
dc.subject.enViral Regulatory and Accessory Proteins
dc.subject.enVirus Replication
dc.title.enThe enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state.
dc.title.alternativeSci Repen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/srep25901en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologieen_US
dc.identifier.pubmed27174370en_US
bordeaux.journalScientific Reportsen_US
bordeaux.page25901en_US
bordeaux.volume6en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04296373
hal.version1
hal.date.transferred2023-11-20T16:02:55Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Scientific%20Reports&rft.date=2016-05-13&rft.volume=6&rft.spage=25901&rft.epage=25901&rft.eissn=2045-2322&rft.issn=2045-2322&rft.au=ALARCON,%20Valentina&HERNANDEZ,%20Sergio&RUBIO,%20Lorena&ALVAREZ,%20Francisca&FLORES,%20Yvo&rft.genre=article


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