PT - JOURNAL ARTICLE AU - Tadahiro Hashita AU - Tsutomu Sakuma AU - Mami Akada AU - Asuka Nakajima AU - Hirofumi Yamahara AU - Sumiyo Ito AU - Hidekazu Takesako AU - Nobuo Nemoto TI - Forkhead Box A2–Mediated Regulation of Female-Predominant Expression of the Mouse <em>Cyp2b9</em> Gene AID - 10.1124/dmd.107.019729 DP - 2008 Jun 01 TA - Drug Metabolism and Disposition PG - 1080--1087 VI - 36 IP - 6 4099 - http://dmd.aspetjournals.org/content/36/6/1080.short 4100 - http://dmd.aspetjournals.org/content/36/6/1080.full SO - Drug Metab Dispos2008 Jun 01; 36 AB - 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 forkhead box A2 (FoxA2) (hepatic nuclear factor 3β)-binding site in this region. Chromatin immunoprecipitation assay indicated that the binding protein to the site was FoxA2 in 5-week-old female mice, whereas this protein was found in both sexes at age 3 weeks, 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, whereas 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. The American Society for Pharmacology and Experimental Therapeutics