title: Transactivation and repression of the alpha-fetoprotein gene promoter by retinoid X receptor and chicken ovalbumin upstream promoter transcription factor.
abstract: Retinoic acid (RA) is widely involved in the control of cell proliferation and differentiation, as well as embryo pattern formation. Transcription of the oncodevelopmental protein, alpha-fetoprotein (AFP), is stimulated by retinoic acid (RA) in neoplastic cells. To study RA regulation of AFP gene expression, the 5'-flanking region of AFP gene was cloned and analyzed. In the present study, transfection of deletion mutants and sequence analysis revealed a retinoid X receptor response element (AFP-RXRE) located at position -139 to -127 of the AFP promoter. Synthetic AFP-RXRE was ligated into a reporter construct with the heterologous promoter and chloramphenicol acetyltransferase (CAT). AFP-RXRE conferred a marked RA responsiveness in the cotransfection with retinoid X receptor (RXR), but not with retinoic acid receptors (RARs). Consistent with these data, only RXR bound to AFP-RXRE with high affinity in the mobility shift assays. Chicken ovalbumin upstream promoter transcription factor (COUP-TF), an orphan member of the steroid/thyroid hormone superfamily, also demonstrated specific binding activity to AFP-RXRE in vitro. In cotransfection assays, COUP-TF dramatically repressed the transactivation of RXR on AFP-RXRE. The mechanism of repression by COUP-TF may involve the mutual occupancy of the AFP-RXRE binding site between RXR and COUP-TF.
authors.affiliation: Department of Biochemistry, University of Vermont College of Medicine, Burlington 05405.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J F
authors.initials: JF
authors.lastname: Chiu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D051838:COUP Transcription Factor I; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D000882:Haplorhini; D007668:Kidney; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013724:Teratoma; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000235:genetics*
chemical_list: D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D000509:alpha-Fetoproteins; D014212:Tretinoin; D015500:Chloramphenicol O-Acetyltransferase