Regulation of the glial-specific JC virus early promoter by the transcription factor Sp1

The regulation of glial-specific JC virus early gene expression was addressed by functional dissection of a previously uncharacterized form of the JC virus promoter (MH-1). The MH-1 promoter directed 31-fold higher reporter gene expression in U87MG glioma cells than in HeLa cells in a transient transfection assay. Transfection of promoter constructs containing proximal or proximal plus upstream regions revealed that reporter gene expression was activated by both proximal and tandem repeat regions in glioma cells. The proximal region contains a guanine-rich sequence, the GA box, which was found to regulate the promoter, and was recognized specifically by the transcription factor Sp1. The GA box is also present in the promoters of three glial-specific cellular genes. Together with paired AP-1 and NF-1 sites in the tandem repeats, the GA box is part of a motif that is conserved between several glial-specific promoters, and is thus a potential determinant of glial-specific gene expression. These results delineate the promoter regions required for activation of the MH-1 JC virus promoter, suggest a new determinant of glial specificity, and establish a model for the investigation of combinatorial activation of a glial-specific viral promoter.