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dc.contributor.authorMäntylä, Elina
dc.contributor.authorSalokas, Kari
dc.contributor.authorOittinen, Mikko
dc.contributor.authorAho, Vesa
dc.contributor.authorMäntysaari, Pekka
dc.contributor.authorPalmujoki, Lassi
dc.contributor.authorKalliolinna, Olli
dc.contributor.authorIhalainen, Teemu O.
dc.contributor.authorNiskanen, Einari A.
dc.contributor.authorTimonen, Jussi
dc.contributor.authorViiri, Keijo
dc.contributor.authorVihinen-Ranta, Maija
dc.date.accessioned2016-05-18T10:52:54Z
dc.date.available2016-05-18T10:52:54Z
dc.date.issued2016
dc.identifier.citationMäntylä, E., Salokas, K., Oittinen, M., Aho, V., Mäntysaari, P., Palmujoki, L., Kalliolinna, O., Ihalainen, T. O., Niskanen, E. A., Timonen, J., Viiri, K., & Vihinen-Ranta, M. (2016). Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection. <i>Journal of Virology</i>, <i>90</i>(8), 4059-4066. <a href="https://doi.org/10.1128/JVI.03160-15" target="_blank">https://doi.org/10.1128/JVI.03160-15</a>
dc.identifier.otherCONVID_25662908
dc.identifier.otherTUTKAID_69804
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/49832
dc.description.abstractThe association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging and in situ proximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that during late infection, parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e., histone H3 lysine 27 acetylation (H3K27ac). H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, the two viral promoters in particular were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitors efficiently interfered with the expression of viral proteins and infection progress. Altogether, our data suggest that the acetylation of histones on parvoviral DNA is essential for viral gene expression and the completion of the viral life cycle. IMPORTANCE Viral DNA introduced into cell nuclei is exposed to cellular responses to foreign DNA, including chromatinization and epigenetic silencing, both of which determine the outcome of infection. How the incoming parvovirus resists cellular epigenetic downregulation of its genes is not understood. Here, the critical role of epigenetic modifications in the regulation of parvovirus infection was demonstrated. We showed for the first time that a successful parvovirus infection is characterized by the deposition of nucleosomes with active histone acetylation on the viral promoter areas. The results provide new insights into the regulation of parvoviral gene expression, which is an important aspect of the development of parvovirus-based virotherapy.
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofseriesJournal of Virology
dc.subject.othercanine parvovirus
dc.subject.otherviral DNA
dc.subject.otherchromatinization
dc.subject.otherhistone acetylation
dc.titlePromoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201605162562
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosFysiikan laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.contributor.laitosDepartment of Physicsen
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.contributor.oppiaineNanoscience Centerfi
dc.contributor.oppiaineCell and Molecular Biologyen
dc.contributor.oppiaineNanoscience Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2016-05-16T12:15:03Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerange4059-4066
dc.relation.issn1098-5514
dc.relation.numberinseries8
dc.relation.volume90
dc.type.versionacceptedVersion
dc.rights.copyright© 2016, American Society for Microbiology. This is a final draft version of an article whose final and definitive form has been published by American Society for Microbiology. Published in this repository with the kind permission of the publisher.
dc.rights.accesslevelopenAccessfi
dc.relation.doi10.1128/JVI.03160-15


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