Nucleic Acids Research, 1994, Vol. 22, No. 7 1242-1246
© 1994
MOLECULAR BIOLOGY |
Activity of the rat liver-specific aldolase B promoter is restrained by HNF3
Institut Cochin de Génétique Moléculaire, Unite 129 de I,INSERM, CHU Cochin 24 rue du Faubourg Saint Jacques, 75014 Paris, France
*To whom correspondence should be addressed
Received November 29, 1993. Revised March 7, 1994. Accepted March 7, 1994.
Although it contains binding sites for HNF1, NFY and C/EBP/DBP, the proximal promoter of the aldolase B gene is surprisingly weak when tested by transient transfectlon in differentiated hepatoma cells. This low activity could be due to overlapping between HNF1 and HNF3 binding sites in element PAB, from –127 to –103 bp with respect to the cap site. Replacement of the PAB region by a consensus HNF1 binding site unable to bind HNF3, results in a 30 fold activation of the promoter, in accordance with the hypothesis that activity of the wild-type promoter is normally restrained by HNF3 binding to PAB competitively with HNF1. Consistently, transactivatlon of the wild-type promoter by excess HNF1 is very high, most likely due to the displacement of HNF3, while the construct with the exclusive HNF1 binding site is weakly transactivated by HNF1. The inhibitory effect of HNF3 on HNF1-dependent transactivatlon is clearly due to competition between these two factors for binding to mutually exclusive, overlapping sites; indeed, when HNF1 and HNF3 sites are contiguous and not overlapping, the resulting promoter is as active as the one containing an exclusive HNF1 binding site. A construct In which PAB has been replaced by an exclusive HNF3 binding site is weakly expressed and is insensitive to HNF3 hyperexpression. DBP-dependent transactivation, finally, is independent of the nature of the element present in the PAB region.
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