Histone modifications associated with herpes simplex virus type 1 genomes during quiescence and following ICP0-mediated de-repression.
In the current study, it was shown that repressed virus genomes in quiescently infected MRC5 cells adopt a repressed histone-associated structure marked by the enrichment of deacetylated histones at a wide variety of herpes simplex virus type 1 (HSV-1) promoters. In addition, it was shown that genome de-repression, mediated by HSV-2 superinfection or delivery of ICP0 using a recombinant adenovirus vector, resulted in the enrichment of acetylated histones on HSV DNA. These data indicate that ICP0-mediated genome de-repression is intimately linked to enrichment of acetylated histones at virus promoters. The fold change in association of pan-acetylated histone H3 following Ad.TRE.ICP0-mediated de-repression consistently revealed promoter-specific variation, with the highest fold changes (>50-fold) being observed at the latency-associated transcript promoter and enhancer regions. Chromatin immunoprecipitation analyses using an antibody specific to the C terminus of histone H3 as a surrogate measure of nucleosome occupancy revealed little variability in the total loading of histone H3 at the various HSV promoters. This observation suggests that acetylation of histone H3 in response to ICP0 expression is not uniformly targeted across the HSV-1 genome during ICP0-mediated de-repression.
Coleman
Heather M
HM
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Connor
Viv
V
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Cheng
Zara S C
ZSC
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Grey
Finn
F
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Preston
Chris M
CM
Medical Research Council Virology Unit, Glasgow G11 5JR, UK.
Efstathiou
Stacey
S
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014775:Virus Activation
D006657:Histones; D017874:Immediate-Early Proteins; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1