Expression of the Pkd1 gene is momentously regulated by Sp1

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. Copyright (C) 2007 S. Karger AG, Basel.