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Nucleic Acids Research, 1989, Vol. 17, No. 23 9833-9842
© 1989

MOLECULAR BIOLOGY

Involvement of an AFP1-binding site in cell-specific transcription of the pre-S1 region of the human hepatitis B virus surface antigen gene

Kazuhiko Nakao, Yasuyoshi Miyao, Yoshihide Ohe and Taiki Tamaoki*

Department of Medical Biochemistry, University of Calgary Calgary, Alberta T2N 4N1, Canada

*To whom correspondence should be addressed

Received July 31, 1989. Revised November 3, 1989. Accepted November 3, 1989.

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.


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