A novel proximal element mediates the regulation of mouse Ren-1C promoter by retinoblastoma protein in cultured cells

The protein product of the retinoblastoma susceptibility gene, RE, is a nuclear phosphoprotein that modulates transcription of genes involved in growth control via interactions with transcription factors. Renin is a rate-limiting enzyme of the renin-angiotensin system that regulates blood pressure and water-electrolyte balance. Renin gene expression is regulated in a tissue-specific and developmentally linked manner. Similarly, the expression of RE is controlled in a differentiation-linked manner, Thus, to investigate whether RE is involved in the regulation of renin gene expression, we examined the effects of RE on transcriptional activity of the mouse renin (Ren-1C) promoter. The Ren-1C promoter contains two transcriptionally important elements; the RU-1 (-224 to -138) and RP-2 (-75 to -47) elements. RE activated the Ren-IC promoter in human embryonic kidney cells. The promoter element responsible for RE-mediated transcriptional regulation was the RP-2 element, The results of DNA-protein binding experiments showed that RE increased nuclear binding activity to the RP-2 element, and site-directed mutation which disrupted binding of nuclear factors to the RP-2 element markedly reduced RE-mediated activation of Ren-IC promoter in human embryonic kidney cells. These results indicate that the RP-2 element plays an important role in RE-mediated transcriptional regulation of Ren-IC promoter activity in human embryonic kidney cells, thereby suggesting an interesting mechanism by which RE may modulate the renin-angiotensin system.