title: High-resolution analysis of CpG methylation and in vivo protein-DNA interactions at the alternative Epstein-Barr virus latency promoters Qp and Cp in the nasopharyngeal carcinoma cell line C666-1.
abstract: Transcripts for the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNAs) are initiated at alternative promoters (Wp, Cp, for EBNA 1-6 transcripts and Qp, for EBNA 1 transcripts only) located in the BamHI W, C or Q fragment of the viral genome. To understand the host-cell dependent expression of EBNAs in EBV-associated tumors (lymphomas and carcinomas) and in vitro transformed cell lines, it is necessary to analyse the regulatory mechanisms governing the activity of the alternative promoters of EBNA transcripts. Such studies focused mainly on lymphoid cell lines carrying latent EBV genomes, due to the lack of EBV-associated carcinoma cell lines maintaining latent EBV genomes during cultivation in tissue culture. We took advantage of the unique nasopharyngeal carcinoma cell line, C666-1, harboring EBV genomes, and undertook a detailed analysis of CpG methylation patterns and in vivo protein-DNA interactions at the latency promoters Qp and Cp. We found that the active, unmethylated Qp was marked with strong footprints of cellular transcription factors and the viral protein EBNA 1. In contrast, we could not detect binding of relevant transcription factors to the methylated, silent Cp. We concluded that the epigenetic marks at Qp and Cp in C666-1 cells of epithelial origin resemble those of group I Burkitt's lymphoma cell lines.
authors.affiliation: Microbiological Research Group, National Center for Epidemiology, Pihenö u. 1, 1529 Budapest, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bakos
authors.forename: Ferenc
authors.initials: F
authors.lastname: Banati
authors.forename: Anita
authors.initials: A
authors.lastname: Koroknai
authors.forename: Maria
authors.initials: M
authors.lastname: Takacs
authors.forename: Daniel
authors.initials: D
authors.lastname: Salamon
authors.forename: Susanna
authors.initials: S
authors.lastname: Minarovits-Kormuta
authors.forename: Fritz
authors.initials: F
authors.lastname: Schwarzmann
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Hans Helmut
authors.initials: HH
authors.lastname: Niller
authors.forename: Janos
authors.initials: J
authors.lastname: Minarovits
mesh_terms: D001483:Base Sequence; D002277:Carcinoma / Q000821:virology*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D017735:Virus Latency / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins