Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2-6.
Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. EBNA 1 is regularly expressed in all Epstein-Barr virus-carrying cells, whereas EBNAs 2-6 are only expressed in Epstein-Barr virus-carrying cells with a lymphoblastoid phenotype including group III Burkitt lymphoma (BL) lines positive for B-cell activation markers. Transcripts are initiated at the BCR2 or exceptionally at one BWR1 promoter in lymphoblastoid cell lines and group III BL lines. In group I BL lines, nasopharyngeal carcinoma, and the somatic cell hybrids, where EBNAs 2-6 are downregulated, the BCR2/BWR1 promoter complex is inactive or switched off. Upregulation of EBNAs 2-6 in group III BL cells and in 5-azacytidine-treated group I BL cells accompanies the activation of the silent BCR2/BWR1 promoters. Activation of BCR2 parallels demethylation of at least one CpG pair in the same promoter region. The activity of BCR2/BWR1 promoter complex depends on a particular B-cell phenotype. EBNA 1 transcription must be initiated at another promoter in cells that express only EBNA 1.
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
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Altiok
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Minarovits
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Hu
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Contreras-Brodin
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Klein
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Ernberg
D000956:Antigens, Viral / Q000235:genetics*; D001374:Azacitidine / Q000494:pharmacology; D001402:B-Lymphocytes / Q000382:microbiology; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000382:microbiology; D004247:DNA / Q000737:chemistry; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D066298:In Vitro Techniques; D008745:Methylation; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000382:microbiology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid
D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012367:RNA, Viral; D004247:DNA; D001374:Azacitidine