Independent regulation of HNF-1 alpha and HNF-1 beta by retinoic acid in F9 teratocarcinoma cells.

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Abstract
Hepatocyte Nuclear Factor‐1 alpha (HNF‐1 alpha) and HNF‐1 beta are homeodomain‐containing transcription factors which interact with the GTTAATNATTAAC motif essential to the function of more than 15 promoters selectively expressed in the liver. These homeoproteins can form homo‐ and heterodimers in solution and share identical DNA‐binding domains but have different transcriptional activation properties. During retinoic acid (RA) induced differentiation of F9 embryonal carcinoma (EC) cells, which stimulates aspects of pre‐implantation embryogenesis, both HNF‐1 beta mRNA and immunoreactive DNA‐binding activity are strongly induced approximately 24 h post RA‐treatment. In contrast, HNF‐1 alpha mRNA increases approximately 4‐fold after 5 days, concomitant with elevation of HNF‐1 alpha DNA‐binding activity and expression of the HNF‐1 target gene alpha‐fetoprotein. These results indicate that HNF‐1 alpha and −1 beta expression can be controlled by regulatory hierarchies downstream of primary RA‐response genes, and suggest that independent regulatory mechanisms for these factors can confer distinct and interactive developmental functions.