Received for publication November 15, 2007.
Revised March 7, 2008.
Accepted for publication March 10, 2008.

FoxA2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene

Abstract

ABSTRACT The regulation mechanism of female-predominant expression of the mouse Cyp2b9 gene was investigated in vivo and in vitro. Luciferase reporter assay revealed that the -234/-194 region of the Cyp2b9 gene may be responsible for sexually dimorphic expression. There is a predicted FoxA2(HNF3)-binding site in this region. Chromatin immunoprecipitation assay indicated that the binding protein to the site was FoxA2 in 5-week-old female mice, while this protein was found in both sexes at 3 weeks old, in accordance with our previous observation on the developmental expression of this gene. Mutation of the predicted FoxA2 site in the reporter construct containing the -234/+18 fragment led to complete elimination of luciferase activity, but deletion of the -234/-194 region resulted in considerable transcriptional activity, suggesting that, by mutating the FoxA2-binding site, a potent suppressor might bind to eliminate activity while, by deleting this region, it could not. Sexually dimorphic secretion of growth hormone is involved in female-predominant expression of the gene, and the -234/-194 region was also responsible for suppressing the expression by male-type secretion.

Key words: CYP expression, CYP gene regulation, CYP2B, gender differences, hormonal regulation, JAK-STAT, sexual dimorphism