Coleman Heather M, Connor Viv, Cheng Zara S C, Grey Finn, Preston Chris M, Efstathiou Stacey
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Medical Research Council Virology Unit, Glasgow G11 5JR, UK.
J Gen Virol. 2008 Jan;89(Pt 1):68-77. doi: 10.1099/vir.0.83272-0.
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.
在当前研究中，结果表明，在静止感染的MRC5细胞中，受抑制的病毒基因组采用一种受抑制的组蛋白相关结构，其特征是在多种单纯疱疹病毒1型（HSV-1）启动子处富含去乙酰化组蛋白。此外，结果表明，由HSV-2超感染或使用重组腺病毒载体递送ICP0介导的基因组去抑制，导致HSV DNA上乙酰化组蛋白的富集。这些数据表明，ICP0介导的基因组去抑制与病毒启动子处乙酰化组蛋白的富集密切相关。在Ad.TRE.ICP0介导的去抑制后，泛乙酰化组蛋白H3结合的倍数变化始终显示出启动子特异性差异，在潜伏期相关转录物启动子和增强子区域观察到最高的倍数变化（>50倍）。使用针对组蛋白H3 C末端的特异性抗体进行染色质免疫沉淀分析，作为核小体占有率的替代指标，结果显示在各种HSV启动子处，组蛋白H3的总负载量变化很小。这一观察结果表明，在ICP0介导的去抑制过程中，响应ICP0表达的组蛋白H3乙酰化并非在HSV-1基因组中均匀靶向。
