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Transcriptional control of the human urothelial-specific gene, uroplakin Ia

Hall, G. D., Weeks, R. J., Olsburgh, J., Southgate, J., Knowles, M. A., Selby, P. J. and Chester, John D. ORCID: 2005. Transcriptional control of the human urothelial-specific gene, uroplakin Ia. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1729 (2) , pp. 126-134. 10.1016/j.bbaexp.2005.04.004

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The transcriptional control elements of tissue-specific genes may be exploited in the design of therapeutic constructs for use in human gene therapy. The uroplakins are a family of four proteins which form the asymmetric unit membrane of the urothelium. We have cloned the human uroplakin Ia gene and defined its genomic structure and transcriptional start site. Using quantitative RT-PCR in an extended panel of normal tissues, we have demonstrated highly urothelial-specific expression of this gene. A Dual-Luciferase assay was used to assess the transcriptional activity of a variety of promoter fragments of the human uroplakin Ia gene. A highly specific promoter fragment (consisting of 2147 bp of 5′-flanking sequence, intron 1 and the 5′ UTR) was identified which regulated urothelial-specific expression in vitro. The human uroplakin Ia promoter identified has potential use in future gene therapy strategies to restrict transgene expression to the urothelium.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Uroplakin 1a; Promoter; Tissue-specific; Urothelial; Gene therapy
Publisher: Elsevier
ISSN: 0167-4781
Last Modified: 19 Oct 2022 08:43

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