Ets factors regulate the polycystic kidney disease-1 promoter

Biochemical and Biophysical Research Communications
Sanjeev PuriJames P Calvet

Abstract

The Ets family of transcription factors consists of a group of highly conserved sequence-specific DNA binding proteins that functionally cooperate with other transcription factors to regulate a number of diverse cellular processes including proliferation, differentiation, and apoptosis. We have analyzed a 3.3kb 5'-upstream region of the human PKD1 promoter, using transient transfection in HEK293T cells and Drosophila SL2 cells, to demonstrate that the PKD1 promoter is a target of Ets family transcription factors. Our studies showed that PKD1 promoter-luciferase reporter gene expression is downregulated by cotransfected Fli-1 and is upregulated by cotransfected Ets-1. Using deletion constructs, we demonstrated that the sequences responding to Fli-1 and Ets-1 lie within the -200 to +33bp proximal promoter. This region was found to contain two putative Ets response elements (EREs): an upstream (Ets-A) sequence 5'-CGGAA-3' (-181 to -185) and a downstream (Ets-B) sequence 5'-CGGAT-3' (-129 to -133). Site-directed mutagenesis indicated that both EREs are functional. A Fli-1 DNA binding domain mutant construct (W321R), which is incapable of binding DNA, was unable to inhibit basal promoter activity. In contrast, a Fli-1 DNA binding do...Continue Reading

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Citations

Oct 17, 2008·American Journal of Physiology. Renal Physiology·M Rafiq IslamJames P Calvet
Apr 15, 2010·Biochimica Et Biophysica Acta·Diederik van BodegomSamir S El Dahr
Nov 6, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kamala P SundararajTamara K Nowling

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