THE RETINOBLASTOMA GENE-PRODUCT ACTIVATES TRANSCRIPTION OF THE HEPATITIS-B VIRUS PREGENOMIC PROMOTER THROUGH THE SP1 BINDING-SITES

The hepatitis B virus (HBV) pregenomic promoter is regulated by two en hancers and cis-elements. We have studied whether the retinoblastoma s usceptibility gene product (Rb) modulates the activity of the HBV preg enomic promoter. Cotransfection of the Rb expression vector, phRB, wit h pCENCAT (containing the pregenomic promoter region: nt 248-1874) inc reased transcription from the HBV pregenomic promoter in HepG2 cells. Deletion analysis of the pregenomic promoter indicated that the region between nt -96 and -66, which contains two Sp1 binding sites, is resp onsible for activation by Rb. Mutation of the Sp1 binding sites abolis hed activation of the pregenomic promoter by Rb in the heterologous an d natural promoter context. Therefore, our results suggest that Rb can activate the HBV pregenomic promoter through the Sp1 binding sites.