Activation of the BRLF1 promoter and lytic cycle of Epstein-Barr virus by histone acetylation.
Histone acetylation alters the chromatin structure and activates the genes that are repressed by histone deacetylation. This investigation demonstrates that treating P3HR1 cells with trichostatin A (TSA) activates the Epstein-Barr virus (EBV) lytic cycle, allowing the virus to synthesize three viral lytic proteins-Rta, Zta and EA-D. Experimental results indicate that TSA and 12-O:-tetradecanoylphorbol-13-acetate synergistically activate the transcription of BRLF1, an immediate-early gene of EBV. Chromatin immunoprecipitation assay reveals that histone H4 at the BRLF1 promoter is acetylated after P3HR1 cells are treated with TSA, suggesting that histone acetylation activates BRLF1 transcription. Furthermore, results in this study demonstrate that mutation of a YY1-binding site in the BRLF1 promoter activates BRLF1 transcription 1.6- and 2.3-fold in P3HR1 cells and C33A cells, respectively. Real time PCR analysis reveals that the mutation also increases the histone acetylation level of the nucleosomes at the BRLF1 promoter 1. 64- and 3.08-fold in P3HR1 and C33A cells, respectively. Results presented herein suggest that histone deacetylation plays an important role in maintaining the viral latency and histone acetylation at the BRLF1 promoter allows the virus to express Rta and to activate the viral lytic cycle.
Chang
L K
LK
Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, Kwei-Shan, Taoyuan 333, Taiwan.
Liu
S T
ST
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D004357:Drug Synergism; D050981:Erythroid-Specific DNA-Binding Factors; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000235:genetics; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000235:genetics*; D009154:Mutation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects; D050986:YY1 Transcription Factor
C068382:BRLF1 protein, Human herpesvirus 4; D002843:Chromatin; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D006657:Histones; D006877:Hydroxamic Acids; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C012589:trichostatin A; D003513:Cycloheximide; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D013755:Tetradecanoylphorbol Acetate