Identification and characterization of an androgen-responsive Kap promoter enhancer located in the intron II region of human angiotensinogen gene.
Identification and characterization of an androgen-responsive Kap promoter enhancer located in the intron II region of human angiotensinogen gene.
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DOI：
10.1016/j.jsbmb.2010.02.005
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发表时间：
2010-04
影响因子：
4.1
通讯作者：
Li, Su-xia
中科院分区：
文献类型：
--
作者：
Fan, Li-qiang;Hardy, Dianne O.;Catterall, James F.;Zhao, Jian;Li, Su-xia
小鼠肾雄激素调节蛋白（Kap）基因启动子介导的人血管紧张素原（HAGT）基因的转基因表达是近端小管细胞特异性和体内雄激素调控的。相同的Kap启动子片段不支持对其他基因的类似调控，但基于原始嵌合Kap - HAGT构建体的转基因成功地将NHE3定向到肾脏，这表明该构建体HAGT基因片段内的序列有助于调节其在体内的表达。在本研究中，在转染的肾细胞中检测了转基因HAGT基因部分的雄激素响应调控序列。在外显子2和3之间发现了一个1.4 kb的增强子，使Kap启动子的基础表达增加1.5 ~ 2倍，双氢睾酮（DHT）诱导量增加2 ~ 3倍，地塞米松（Dex）诱导量增加4 ~ 5倍。序列分析揭示了两个潜在的激素响应元件。突变分析和电泳迁移迁移分析表明，其中一个元件是雄激素特异性的。这些发现可能会影响未来设计可诱导的、细胞特异性转基因的策略。
Transgenic expression of the human angiotensinogen (HAGT) gene directed by the mouse kidney androgen-regulated protein (Kap) gene promoter is proximal tubule cell-specific and androgen-regulated in vivo. The same Kap promoter fragment did not support similar regulation of other genes, but a transgene based on the original chimeric KAP-hAGT construct successfully directed NHE3 to kidney, suggesting that sequences within the HAGT gene fragment of the construct contributed to the regulation of its expression in vivo. In the present study, androgen-responsive regulatory sequences in the HAGT gene portions of the transgene were examined in transfected renal cells. A 1.4 kb enhancer between exons 2 and 3 was identified that increased the basal expression of Kap promoter 1.5 to 2-fold, its induction by dihydrotestosterone (DHT) 2 to 3-fold and its induction by dexamethasone (Dex) 4 to 5-fold. Sequence analysis revealed two potential hormone responsive elements. Mutational assays and electrophoretic mobility shift assay showed one of these elements was androgen-specific. These findings may influence future strategies for the design of inducible, cell-specific transgenes.
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影响因子：
3.7
作者：
Fan, Liqiang;Hardy, Dianne O.;Li, Suxia
通讯作者：
Li, Suxia
影响因子：
4.1
作者：
Hardy, DO;Niu, EM;Catterall, JF
通讯作者：
Catterall, JF
影响因子：
--
作者：
Hsu, CL;Chen, YL;Chang, CS
通讯作者：
Chang, CS
DOI：
10.1016/s0960-0760(00)00154-0
发表时间：
2001-01-01
影响因子：
4.1
作者：
Claessens, F;Verrijdt, G;Rombauts, W
通讯作者：
Rombauts, W
DOI：
10.1073/pnas.85.3.836
发表时间：
1988-02-01
影响因子：
11.1
作者：
BRINSTER, RL;ALLEN, JM;PALMITER, RD
通讯作者：
PALMITER, RD