The HNF-3alpha transcription factor is a primary target for retinoic acid action.
We have previously demonstrated that gene expression of the hepatocyte nuclear factor 3alpha (HNF-3alpha) transcription factor is activated during retinoic-acid-induced differentiation of F9 embryonal carcinoma cells (A. Jacob et al. (1994). Nucleic Acids Res. 22, 2126-2133). We have extended these studies and now show that HNF-3alpha mRNA is induced approximately 6 h after addition of retinoic acid to the cells, peaks at 1 day postdifferentiation, and then declines to undetectable levels. Furthermore, HNF-3alpha induction occurs in the absence of de novo protein synthesis, suggesting that it is a primary target for retinoic acid action. In order to corroborate this hypothesis, we have mapped the cis-acting HNF-3alpha promoter site that mediates the retinoic acid response. DNA sequence analysis indicates that the HNF-3alpha promoter contains an authentic retinoic acid response element (RARE) of the DR5 class. As expected, this element is able to confer retinoic acid responsiveness to a heterologous promoter. In addition, the HNF-3alpha-specific RARE is able to interact with various retinoic acid receptor heterodimers of the RAR/RXR type. Since HNF-3alpha is induced early during mammalian neurogenesis, our data shed new light on the connection between retinoic-acid-mediated HNF-3alpha activation and establishment of the neuronal phenotype.
Jacob
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A
Department of Cellular and Molecular Pharmacology, The Chicago Medical School, North Chicago, Illinois, 60064, USA.
Budhiraja
S
S
Reichel
R R
RR
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D051541:Hepatocyte Nuclear Factor 3-alpha; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020218:Response Elements; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C496499:FOXA1 protein, human; C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D009687:Nuclear Proteins; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin