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 ad dressed by functional dissection of a previously uncharacterized form of the JC virus promoter (MH-1). The MH-1 promoter directed 31-fold hi gher reporter gene expression in U87MG glioma cells than in HeLa cells in a transient transfection assay. Transfection of promoter construct s containing proximal or proximal plus upstream regions revealed that reporter gene expression was activated by both proximal and tandem rep eat regions in glioma cells. The proximal region contains a guanine-ri ch sequence, the GA box, which was found to regulate the promoter, and was recognized specifically by the transcription factor Spl. The GA b ox is also present in the promoters of three glial-specific cellular g enes. 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-speci fic gene expression. These results delineate the promoter regions requ ired for activation of the MH-I JC virus promoter, suggest a new deter minant of glial specificity, and establish a model for the investigati on of combinatorial activation of a glial-specific viral promoter.