The transcriptional enhancer element, kappa B, regulates promoter activity of the human neurotropic virus, JCV, in cells derived from the CNS.
Studies on the regulation of the human neurotropic virus (JCV) promoter, have been focused primarily on the 98 bp tandem repeat sequence which confers glial-specificity to viral gene expression. We demonstrate that a distinct regulatory element outside of the 98 bp region, which spans a stretch of 10 nucleotides (nt) (5'-GGGAATTTCC-3') increases transcriptional activity of JCV late (JCVL), and early (JCVE) promoters in glial cells. Sequence analysis of this motif reveals extensive homology to the kappa B sequence of HIV-1 (5'-GGGACTTTCC-3'). A DNA fragment corresponding to the 10 nt sequence of JCV exhibits transcriptional activity when placed upstream of the test promoter in glial cells. The induction mediated by this regulatory motif is moderately enhanced in response to phorbol 12-myristate 13-acetate (PMA) in glial cells. Band-shift and UV-crosslinking experiments suggest that glial cells constitutively produce proteins that specifically interact with the JCV kappa B, but not the HIV-1 kappa B motif. Treatment of cells with PMA results in formation of new complexes that are sensitive to the kappa B sequences derived from the JCV and HIV-1 genomes. These results suggest that the kappa B sequence located in the JCV genome may play a role in transcriptional regulation of JCV gene expression by interacting with inducible and uninducible nuclear proteins from glial cells.
Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107.
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Ranganathan
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Khalili
D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007577:JC Virus / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000382:microbiology; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D016328:NF-kappa B