Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene.
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 3beta)-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.
Hashita
Tadahiro
T
Department of Toxicology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Sakuma
Tsutomu
T
Akada
Mami
M
Nakajima
Asuka
A
Yamahara
Hirofumi
H
Ito
Sumiyo
S
Takesako
Hidekazu
H
Nemoto
Nobuo
N
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D000072467:Cytochrome P450 Family 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter / Q000235:genetics; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics; D013250:Steroid Hydroxylases / Q000235:genetics*
C496503:Foxa2 protein, mouse; D012333:RNA, Messenger; D051542:Hepatocyte Nuclear Factor 3-beta; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C121503:Cyp2b9 protein, mouse; D000072467:Cytochrome P450 Family 2