The HNF-3α Transcription Factor Is a Primary Target for Retinoic Acid Action

Abstract We have previously demonstrated that gene expression of the hepatocyte nuclear factor 3α (HNF-3α) 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-3α 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-3α 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-3α promoter site that mediates the retinoic acid response. DNA sequence analysis indicates that the HNF-3α 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-3α-specific RARE is able to interact with various retinoic acid receptor heterodimers of the RAR/RXR type. Since HNF-3α is induced early during mammalian neurogenesis, our data shed new light on the connection between retinoic-acid-mediated HNF-3α activation and establishment of the neuronal phenotype.