Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur alpha in glial cells.
Transcription of the human polyomavirus (JCV) genome is regulated by host cell proteins and the viral early protein, T antigen. A region called the lytic control element (LCE), located within the enhancer of JCV, is important for transcription of JCV early and late promoters. Earlier studies have led to the identification of two single-stranded DNA-binding proteins, YB-1 and Pur alpha, with the ability to interact with nucleotides on the early and late strands of LCE, respectively. Of particular interest is the notion that the unique interplay between these two cellular proteins and JCVT antigen determines their binding activities with the LCE. In this study, we employed a series of cotransfection experiments to evaluate the levels of transcription from JCV early and late promoters in the presence of YB-1, Pur alpha, and T antigen. Results from these studies indicated that Pur alpha stimulates JCV early and has little effect on the late promoter. Moreover, T antigen was able to decrease the induced level of early gene transcription by Pur alpha. On the other hand, the extent of transactivation of the viral late promoter by T antigen was reduced upon overexpression of Pur alpha in the transfected cells. These observations suggest that Pur alpha and T antigen exert an antagonistic effect on each other's regulatory action upon their responsive promoters. Of particular interest was the observation that YB-1 liberated T-antigen-induced late promoter activity from repression imposed by overexpression of pur alpha. Under similar conditions, overexpression of YB-1 showed no effect on the transcriptional activity of the early promoter in cells transfected with T-antigen- and Pur alpha-producing plasmids. On the basis of the data presented here and the previous binding results, a model is proposed which describes the potential role of Pur alpha, YB-1, and T antigen in differential expression of the viral genome during the lytic cycle.
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Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Khalili
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D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009457:Neuroglia / Q000378:metabolism*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D051840:Y-Box-Binding Protein 1
D000952:Antigens, Polyomavirus Transforming; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; C501130:PURA protein, human; D011994:Recombinant Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D015500:Chloramphenicol O-Acetyltransferase