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Exp Cell Res. 1999 Jul 10;250(1):1-9.

The HNF-3alpha transcription factor is a primary target for retinoic acid action.

Author information

1
Department of Cellular and Molecular Pharmacology, The Chicago Medical School, North Chicago, Illinois, 60064, USA.

Abstract

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.

PMID:
10388516
DOI:
10.1006/excr.1999.4512
[Indexed for MEDLINE]

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