title: Control of human cytomegalovirus gene expression by differential histone modifications during lytic and latent infection of a monocytic cell line.
abstract: Non-differentiated THP-1 cells can be infected by human cytomegalovirus (HCMV) Towne strain, which persists in these cells in a non-active (latent) form without undergoing a productive cycle. The same cells become permissive for HCMV lytic infection after induction of cell differentiation by treatment with 12-O-tetradecanoylphorbol-13-acetate. We used this cellular model to study the possible role of histone modifications in the control of HCMV latency. Using chromatin immunoprecipitation with antibodies against histone H3 acetylated or dimethylated in position K9, we demonstrated that in lytically infected cells the HCMV enhancer was associated with heavy acetylated but not dimethylated H3. In the case of latent infection, the HCMV enhancer was associated with neither acetylated nor dimethylated H3. HCMV genes encoding DNA polymerase (early), pp65 (early-late) and pp150 (late) proteins were associated preferentially with acetylated H3 in lytically infected cells and with dimethylated H3 in latently infected cells. These data strongly suggest that K9 methylation of H3 is involved in HCMV gene repression, while association of the above genes with acetylated histones is likely to be necessary for active transcription. It can be postulated that the same histone modifications are used to mark active and repressed genes in both cellular and viral chromatin.
authors.affiliation: Microbiology Section, Department of Pathology and Laboratory Medicine, University of Parma, Viale Antonio Gramsci, 14, 43100 Parma, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ioudinkova
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Arcangeletti
authors.forename: Alla
authors.initials: A
authors.lastname: Rynditch
authors.forename: Flora
authors.initials: F
authors.lastname: De Conto
authors.forename: Federica
authors.initials: F
authors.lastname: Motta
authors.forename: Silvia
authors.initials: S
authors.lastname: Covan
authors.forename: Federica
authors.initials: F
authors.lastname: Pinardi
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Razin
authors.forename: Carlo
authors.initials: C
authors.lastname: Chezzi
mesh_terms: D000107:Acetylation; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D003587:Cytomegalovirus / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009000:Monocytes / Q000821:virology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D017735:Virus Latency / Q000235:genetics*
chemical_list: D006657:Histones; D013755:Tetradecanoylphorbol Acetate