Identification and characterization of an androgen-responsive Kap promoter enhancer located in the intron II region of human angiotensinogen gene

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• 作者：Li-qiang Fan ; Dianne O. Hardy ; James F. Catterall ; Jian Zhao ; Su-xia Li
• 关键词：Androgen ; Glucocorticoid ; Enhancer ; Gene regulation ; hAGT ; Kap promoter
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2010
• 出版时间：April 2010
• 年：2010
• 卷：119
• 期：3-5
• 页码：135-140
• 全文大小：510 K

文摘

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.