title: The histone variant H3.3 regulates gene expression during lytic infection with herpes simplex virus type 1.
abstract: It has been proposed that incorporation of the histone variant H3.3 within actively transcribed regions of a genome helps to facilitate transcription. In this report we use lytic infection by herpes simplex virus type 1 (HSV-1) as a model to examine the temporal profile of histone H3 incorporation and to determine whether the variant histone H3.3 has a direct effect on transcription. We find that canonical H3.1 and variant H3.3 exhibit distinct temporal associations with the genome in cell lines expressing equal amounts of epitope-tagged H3 variants. At the earliest times examined after infection, the HSV-1 genome is incorporated into chromatin that predominantly contains the variant H3.3, whereas incorporation of canonical H3.1 occurs later in infection and is dependent on replication of the HSV-1 genome. Further, inhibition of H3.3 association, via reduced expression of the H3.3 chaperone HIRA, significantly reduces the levels of HSV-1 mRNA. These findings show that incorporation of H3.3 facilitates transcription, and they provide new evidence for a regulatory role of chromatin composition during HSV-1 acute infection.
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennysylvania 19104, USA.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Placek
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Kent
authors.forename: Jean
authors.initials: J
authors.lastname: Dorsey
authors.forename: Lyndi
authors.initials: L
authors.lastname: Rice
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Fraser
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
mesh_terms: D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005814:Genes, Viral; D006367:HeLa Cells; D006561:Herpes Simplex / Q000235:genetics*; D006657:Histones / Q000502:physiology*; D006801:Humans; D034741:RNA, Small Interfering; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
chemical_list: D006657:Histones; D034741:RNA, Small Interfering