Involvement of an AFP1-binding site in cell-specific transcription of the pre-S1 region of the human hepatitis B virus surface antigen gene.
Human hepatitis B virus infection is characterized by a high degree of hepatotropism which may be due to the dependency of viral genes on specific host factors for their expression. To learn more about such a requirement and the molecular basis of the viral tissue tropism we analyzed the promoter function in the pre-S1 region of the surface antigen gene. DNase I footprinting and competition gel retardation assays showed that a sequence with an AT-rich core (AT motif) in the pre-S1 promoter region interacts with AFP1, a hepatoma nuclear factor that binds to the alpha-fetoprotein enhancer and promoter. Functional analysis of the pre-S1 AT motif by transient transfection assays showed that this element is important in cell-specific transcriptional initiation. These results suggest that AFP1 may be one of the factors determining the liver specificity of human hepatitis B virus.
Nakao
K
K
Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
Miyao
Y
Y
Ohe
Y
Y
Tamaoki
T
T
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005814:Genes, Viral; D006367:HeLa Cells / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015678:Viral Structural Proteins / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism
D006514:Hepatitis B Surface Antigens; D009687:Nuclear Proteins; D015678:Viral Structural Proteins; D000509:alpha-Fetoproteins