TitleTissue-specific transcription of the mouse alpha-fetoprotein gene promoter is dependent on HNF-1.
Publication TypeJournal Article
Year of Publication1989
AuthorsFeuerman, MH, Godbout, R, Ingram, RS, Tilghman, SM
JournalMol Cell Biol
Date Published1989 Oct
Keywordsalpha-Fetoproteins, Animals, Base Sequence, Deoxyribonuclease I, DNA Mutational Analysis, DNA-Binding Proteins, Humans, Liver, Mice, Nuclear Proteins, Organ Specificity, Poly A, Promoter Regions, Genetic, Recombinant Fusion Proteins, RNA, Messenger, Sequence Homology, Nucleic Acid, Thymidine Kinase, Transcription Factors

Previous work identified four upstream cis-acting elements required for tissue-specific expression of the alpha-fetoprotein (AFP) gene: three distal enhancers and a promoter. To further define the role of the promoter in regulating AFP gene expression, segments of the region were tested for the ability to direct transcription of a reporter gene in transient expression assay. Experiments showed that the region within 250 base pairs of the start of transcription was sufficient to confer liver-specific transcription. DNase I footprinting and band shift assays indicated that the region between -130 and -100 was recognized by two factors, one of which was highly sequence specific and found only in hepatoma cells. Competition assays suggested that the liver-specific binding activity was HNF-1, previously identified by its binding to other liver-specific promoters. Mutation of the HNF-1 recognition site at -120 resulted in a significant reduction in transcription in transfection assays, suggesting a biological role for HNF-1 in the regulation of AFP expression.

Alternate JournalMol. Cell. Biol.