T antigen of human papovavirus JC stimulates transcription of the POU domain factor Tst-1/Oct6/SCIP.
Human papovavirus JC exhibits a strong tropism for glial cells in vivo. To a large extent, this effect is due to the pronounced glia specificity of viral gene expression, which is mediated by the specific interaction of glial transcription factors such as Tst-1/Oct6/SCIP with viral promoter sequences. Here we show that, in return, expression of the glial transcription factor Tst-1/Oct6/SCIP can be strongly activated by T antigen, the early gene product of JC virus, in a dose-dependent manner. In transient transfection experiments, stimulation by T antigen was entirely dependent on a 335-bp segment of the Tst-1/Oct6/SCIP gene promoter that included the transcriptional start site. The same fragment was also bound by purified T antigen in immunoprecipitation assays due to the presence of three closely spaced and tandemly oriented GAGGC pentamers. However, when this array of pentamers was mutated so that binding of T antigen was strongly reduced, T-antigen-dependent transcriptional activation remained unaffected. Thus, similar to viral late gene expression, transcriptional stimulation of the Tst-1/Oct6/SCIP gene by T antigen was not dependent on binding to GAGGC pentamers present within the promoter. Nevertheless, our data provide strong support for a model in which JC virus influences gene expression of its host cell via its early gene product in a manner favourable for its own propagation.
Renner
K
K
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany.
Sock
E
E
Gerber
J K
JK
Wegner
M
M
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005909:Glioblastoma; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D050816:Octamer Transcription Factor-6; D011993:Recombinant Fusion Proteins; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; C494178:POU3F1 protein, human; C494180:Pou3f1 protein, mouse; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6