alexa Expression of the Pkd1 gene is momentously regulated by Sp1.


Biochemistry & Physiology: Open Access

Author(s): Jeon JO, Yoo KH, Park JH

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Abstract BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic disease that is caused by a mutation of a single gene inherited from either parent. Mutations in the Pkd1 gene result in the formation of multiple fluid-filled cysts in kidneys. In previous studies, the functional regulatory sequences of Pkd1 promoter region were detected by the use of comparative genome analysis. METHODS: To investigate the transcriptional regulation of the Pkd1 gene, the Pkd1 promoter was isolated. This promoter contains three Sp1-binding sites. Two of the sites which are found in a 300 bp fragment (-127 to +157) were mutated. An electrophoretic mobility shift assay (EMSA) was performed to determine which transcription factors are bound to Pkd1. RESULTS: Based on studies using a luciferase assay, the Sp1-A site (the nearest Sp1 to the ATG start codon) is more important for activation of Pkd1. The result of EMSA showed that Sp1 transcription factor binds with Pkd1 promoter regions. CONCLUSIONS: Two of the Sp1 sites were found in a proximal promoter region of Pkd1 (-127 to +157). Sp1 sites affect an important role in the activation of the gene. Especially, the Sp1-A site is more important for expression of Pkd1. (c) 2007 S. Karger AG, Basel. This article was published in Nephron Exp Nephrol and referenced in Biochemistry & Physiology: Open Access

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