CHARACTERIZATION OF THE MINIMAL ELEMENTS OF THE HEPATITIS-B VIRUS LARGE SURFACE-ANTIGEN PROMOTER

It has been demonstrated that the hepatocyte nuclear factor 1 (HNF1) b inding site is critical for the majority of the hepatitis B virus (HBV ) large surface antigen promoter activity in differentiated hepatoma c ell lines. Examination of a series of clustered point mutations in the minimal large surface antigen promoter demonstrated that the HNF1 and TATA box binding sites are the major regulatory elements required for transcription from this promoter. Synthetic promoter constructs conta ining the large surface antigen promoter HNF1 binding site and TATA bo x element upstream of the luciferase open reading frame were tested fo r their transcriptional activities in HepG2. 1 cells in the absence or presence of an HNF1 expression vector. These synthetic promoter const ructs displayed a similar level of transcriptional activity and induct ion by HNF1 in comparison with the full-length large surface antigen p romoter, suggesting that additional HBV sequences are dispensable for full transcriptional activity. The distance between the HNF1 binding s ite and TATA box element in the synthetic promoter constructs appeared to influence the transcriptional activity modestly and in a periodic manner.