The HNF-3 alpha transcription factor is a primary target for retinoic acidaction

We have previously demonstrated that gene expression of the hepatocyte nucl ear factor 3 alpha (HNF-3 alpha) transcription factor is activated during r etinoic-acid-induced differentiation of F9 embryonal carcinoma cells (A Jac ob et al. (1994). Nucleic Acids Res. 22, 2126-2133), We have extended these studies and now show that HNF-3 alpha mRNA is induced approximately 6 h af ter addition of retinoic acid to the cells, peaks at 1 day postdifferentiat ion, and then declines to undetectable levels. Furthermore, HNF-3 alpha ind uction occurs in the absence of de novo protein synthesis, suggesting that it is a primary target for retinoic acid action, In order to corroborate th is hypothesis, we have mapped the cis-acting HNF-3 alpha promoter site that mediates the retinoic acid response. DNA sequence analysis indicates that the HNF-3 alpha promoter contains an authentic retinoic acid response eleme nt (RARE) of the DR5 class. As expected, this element is able to confer ret inoic acid responsiveness to a heterologous promoter, In addition, the HNF- 3 alpha-specific RARE is able to interact with various retinoic acid recept or heterodimers of the RAR/RXR type. Since HNF-3 alpha is induced early dur ing mammalian neurogenesis, our data shed new light on the connection betwe en retinoic-acid-mediated HNF-3 alpha activation and establishment of the n euronal phenotype. (C) 1999 Academic Press.