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DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity

dc.contributor.authorNAUGHTIN, Monica
dc.contributor.authorHAFTEK-TERREAU, Zofia
dc.contributor.authorXAVIER, Johan
dc.contributor.authorMEYER, Sam
dc.contributor.authorSILVAIN, Maud
dc.contributor.authorJASZCZYSZYN, Yan
dc.contributor.authorLÉVY, Nicolas
dc.contributor.authorMIELE, Vincent
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBENLEULMI, Mohamed
dc.contributor.authorRUFF, Marc
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPARISSI, Vincent
dc.contributor.authorVAILLANT, Cédric
dc.contributor.authorLAVIGNE, Marc
dc.date.accessioned2023-07-18T08:40:34Z
dc.date.available2023-07-18T08:40:34Z
dc.date.issued2015
dc.identifier.issn1932-6203
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/183424
dc.description.abstractEnRetroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation. We have developed a new in vitro integration assay using physiologically-relevant, reconstituted genomic acceptor chromatin and high-throughput determination of nucleosome positions and integration sites, in parallel. A quantitative analysis of the resulting data reveals a chromatin-dependent redistribution of the integration sites and establishes a link between integration sites and nucleosome positions. The co-activator LEDGF/ p75 enhanced integration but did not modify the integration sites under these conditions. We also conducted an in cellulo genome-wide comparative study of nucleosome positions and human immunodeficiency virus type-1 (HIV-1) integration sites identified experimentally in vivo. These studies confirm a preferential integration in nucleosome-covered regions. Using a DNA mechanical energy model, we show that the physical properties of DNA probed by IN binding are important in determining IN selectivity. These novel in vitro and in vivo approaches confirm that IN has a preference for integration into a nucleosome, and suggest the existence of two levels of IN selectivity. The first depends on the physical properties of the target DNA and notably, the energy required to fit DNA into the IN catalytic pocket. The second depends on the DNA deformation associated with DNA wrapping around a nucleosome. Taken together , these results indicate that HIV-1 IN is a shape-readout DNA binding protein.
dc.language.isoen
dc.publisherPublic Library of Science
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enDNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pone.0129427
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]
bordeaux.pagee0129427
bordeaux.volume10
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
bordeaux.import.sourcehal
hal.identifierpasteur-01416841
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.date=2015&rft.volume=10&rft.spage=e0129427&rft.epage=e0129427&rft.eissn=1932-6203&rft.issn=1932-6203&rft.au=NAUGHTIN,%20Monica&HAFTEK-TERREAU,%20Zofia&XAVIER,%20Johan&MEYER,%20Sam&SILVAIN,%20Maud&rft.genre=article


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