Roles of the Nuclear Lamina in Stable Nuclear Association and Assembly of a Herpesviral Transactivator Complex on Viral Immediate-Early Genes

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Roles of the Nuclear Lamina in Stable Nuclear Association and Assembly of a Herpesviral Transactivator Complex on Viral Immediate-Early Genes

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dc.contributor.author Silva, Lindsey
dc.contributor.author Chang, Lynne
dc.contributor.author Triezenberg, Steven J.
dc.contributor.author Oh, Hyung Suk
dc.contributor.author Yan, Zhipeng
dc.contributor.author Knipe, David Mahan
dc.date.accessioned 2012-08-09T13:15:06Z
dc.date.issued 2012
dc.identifier.citation Silva, Lindsey, Hyung Suk Oh, Lynne Chang, Zhipeng Yan, Steven J. Triezenberg, and David M. Knipe. 2012. Roles of the nuclear lamina in stable nuclear association and assembly of a herpesviral transactivator complex on viral immediate-early genes. mBio 3(1): e00300-11. en_US
dc.identifier.issn 2150-7511 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9385638
dc.description.abstract ABSTRACT: Little is known about the mechanisms of gene targeting within the nucleus and its effect on gene expression, but most studies have concluded that genes located near the nuclear periphery are silenced by heterochromatin. In contrast, we found that early herpes simplex virus (HSV) genome complexes localize near the nuclear lamina and that this localization is associated with reduced heterochromatin on the viral genome and increased viral immediate-early (IE) gene transcription. In this study, we examined the mechanism of this effect and found that input virion transactivator protein, virion protein 16 (VP16), targets sites adjacent to the nuclear lamina and is required for targeting of the HSV genome to the nuclear lamina, exclusion of heterochromatin from viral replication compartments, and reduction of heterochromatin on the viral genome. Because cells infected with the VP16 mutant virus in1814 showed a phenotype similar to that of lamin \(A/C^{−/−}\) cells infected with wild-type virus, we hypothesized that the nuclear lamina is required for VP16 activator complex formation. In lamin \(A/C^{−/−}\) mouse embryo fibroblasts, VP16 and Oct-1 showed reduced association with the viral IE gene promoters, the levels of VP16 and HCF-1 stably associated with the nucleus were lower than in wild-type cells, and the association of VP16 with HCF-1 was also greatly reduced. These results show that the nuclear lamina is required for stable nuclear localization and formation of the VP16 activator complex and provide evidence for the nuclear lamina being the site of assembly of the VP16 activator complex. en_US
dc.language.iso en_US en_US
dc.publisher American Society for Microbiology en_US
dc.relation.isversionof doi:10.1128/mBio.00300-11 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258183/pdf/ en_US
dash.license LAA
dc.title Roles of the Nuclear Lamina in Stable Nuclear Association and Assembly of a Herpesviral Transactivator Complex on Viral Immediate-Early Genes en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal mBio en_US
dash.depositing.author Oh, Hyung Suk
dc.date.available 2012-08-09T13:15:06Z

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