Transgenic Mice Demonstrate Novel Promoter Regions for Tissue-Specific Expression of the Urokinase Receptor Gene
| Autor: | Chunhong Yan, John Hicks, Heng Wang, Douglas D. Boyd, Yao Wang, Sun Jin Kim, Parham Khanbolooki |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Colon Placenta Transgene Mice Transgenic Receptors Cell Surface Biology Receptors Urokinase Plasminogen Activator Pathology and Forensic Medicine Mice Plasminogen Activators Upstream activating sequence Genes Reporter Gene expression Animals Tissue Distribution Promoter Regions Genetic Gene Epididymis Regulation of gene expression Promoter Molecular biology Chromatin Gene Expression Regulation Regulatory sequence Female Regular Articles |
| Zdroj: | The American Journal of Pathology. 163:453-464 |
| ISSN: | 0002-9440 |
| Popis: | The urokinase-type plasminogen activator receptor (u-PAR) contributes to cell migration and proteolysis in normal and cancerous tissues. Currently, there are no reports on the regulatory regions directing tissue-specific expression. Consequently, we undertook a study to identify novel promoter regions required for expression of this gene in transgenic mice bearing a LacZ reporter regulated by varying amounts (0.4, 1.5, and 8.5 kb) of upstream sequence. The 0.4-kb u-PAR upstream sequence directed weak and strong LacZ expression in the placenta and epididymis, respectively, both of which are tissues that express endogenous u-PAR. Conversely, transgene expression in the apical cells of the colon positive for endogenous u-PAR protein required 1.5 kb of upstream sequence for optimal expression. Furthermore, chromatin accessibility assays coupled with real-time polymerase chain reaction suggested a putative regulatory region spanning −1295/−1192 driving u-PAR expression in colonic cells. Interestingly, placental transgene expression was augmented with the 8.5-kb upstream fragment compared with the shorter 1.5-kb fragment indicating contributing element(s) between −1.5 and −8.5 kb. Thus, while 0.4 kb of upstream sequence directs u-PAR expression in the epididymis, sequences located between −0.4 and −1.5 kb and between −1.5 and −8.5 kb are required for optimal tissue-specific expression in the colon and the placenta, respectively. |
| Databáze: | OpenAIRE |
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