Negative regulation of the hepatitis B virus pre-S1 promoter by internal DNA sequences.
Expression of the surface antigen gene (S gene) of hepatitis B virus is directed by two distinct promoter elements with markedly different activities. The upstream (pre-S1) promoter produces a 2.4-kb transcript at very low levels while the downstream (pre-S2) promoter produces an approximately 2.1-kb transcript in relative abundance. We have constructed a series of internal deletion mutants to analyze differential regulation of the two S gene promoters. We show here that expression directed by the pre-S1 promoter is negatively regulated by DNA sequences containing the downstream pre-S2 promoter region. Nuclear run-on analysis indicates this down-regulation to be at the level of transcription. Furthermore, promoter repression does not appear to be due to products of the S gene region. Deletion mutagenesis studies have permitted the localization of a 61-bp region that may be involved in the apparent down-regulation of the pre-S1 promoter. These results suggest the use of an unusual regulatory mechanism by a dipromoter gene in which an active internal promoter may preclude efficient use of an upstream promoter.
Bulla
G A
GA
Department of Microbiology and Immunology, University of Colorado School of Medicine, Denver 80262.
Siddiqui
A
A
D001483:Base Sequence; D015152:Blotting, Northern; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D008099:Liver / Q000502:physiology; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens