Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene
Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene
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DOI：
10.1124/dmd.107.019729
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发表时间：
2008-06-01
影响因子：
3.9
通讯作者：
Nemoto, Nobuo
中科院分区：
文献类型：
--
作者：
Hashita, Tadahiro;Sakuma, Tsutomu;Nemoto, Nobuo
在体内和体外研究了小鼠Cyp 2b 9基因雌性优势表达的调控机制。荧光素酶报告基因分析表明Cyp 2b 9基因的-234/-194区域可能是导致性二态表达的原因。在该区域有一个预测的叉头框A2（FoxA 2）（肝核因子3 β）结合位点。染色质免疫沉淀分析表明，该网站的结合蛋白是FoxA 2在5周龄的雌性小鼠，而这种蛋白质被发现在两种性别在3周龄，根据我们以前的观察，该基因的发育表达。在含有-234/+18片段的报告构建体中，预测的FoxA 2位点的突变导致荧光素酶活性的完全消除，但-234/-194区域的缺失导致相当大的转录活性，这表明通过突变FoxA 2结合位点，有效的抑制剂可能结合以消除活性，而通过缺失该区域则不能。生长激素的性二型分泌参与了该基因的雌性优势表达，并且-234/-194区域也负责抑制雄性型分泌的表达。
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 3 beta)-binding site in this region. Chromatin immuno-precipitation 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.