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.
Jeon
Jeong Ok
JO
Department of Biological Science, Sookmyung Women's University, Seoul, Korea.
Yoo
Kyung Hyun
KH
Park
Jong Hoon
JH
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016891:Polycystic Kidney, Autosomal Dominant / Q000201:enzymology* / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D050396:TRPP Cation Channels / Q000378:metabolism*
D016329:Sp1 Transcription Factor; D050396:TRPP Cation Channels