Sep 11, 2001

Glucocorticoid stimulates primate but inhibits rodent alpha-fetoprotein gene promoter

Biochemical and Biophysical Research Communications
Hidekazu NakabayashiShinzo Nishi


Glucocorticoids inhibit rodent alpha-fetoprotein (AFP) gene activity but stimulate expression of the human homologue. Like human, activity of the AFP promoter from other primates was stimulated by the synthetic glucocorticoid dexamethasone (Dex) in various cell lines. A glucocorticoid responsive element (GRE) is located within 180 bp upstream of the transcription initiation site of all AFP genes examined. Comparative analysis of the GRE in the two different groups of promoters revealed a common 3' hexamer, 5'-TGTCCT-3', but the 5' hexamers were different. This difference converts the rodent GRE to a DR-1 motif. DR-1 is a binding site for members of the nuclear receptor superfamily including the orphan receptor hepatocyte nuclear factor-4 (HNF-4). The presence of DR-1 in the rodent but not human may underlie the opposite actions of Dex on the AFP promoter. We tested this hypothesis using a transient transfection assay. In hepatoma cells that expressed GR and HNF-4, reporter-activity was inhibited by Dex. The same construct in nonhepatoma cells was strongly induced by over expression of HNF-4 and the induced activity was inhibited by Dex. The findings show that Dex induction of human AFP is mediated by a GRE. But Dex repression o...Continue Reading

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Mentioned in this Paper

Tcfl4 protein, mouse
Glucocorticoid inhalants for obstructive airway disease
Transcription Initiation Site
Pongo pygmaeus pygmaeus
COS-7 Cells
Liver Carcinoma
Fetal Proteins
Hepatocyte Nuclear Factor 4-beta

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