Retinoic acid (RA) is widely involved in the control of cell proliferation and differentiation, as well as embryo pattern formation. Transcription of the oncodevelop-mental protein, α-fetoprotein (AFP), is stimulated by retlnoic 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 retinolc 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 super-family, 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. © 1994 Oxford University Press.
CITATION STYLE
Liu, Y., & Chiu, J. fu. (1994). Transactivation and repression of the α-fetoprotein gene promoter by retinoid X receptor and chicken ovalbumin upstream promoter transcription factor. Nucleic Acids Research, 22(6), 1079–1086. https://doi.org/10.1093/nar/22.6.1079
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