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 involve d in growth control via interactions with transcription factors. Renin is a rate-limiting enzyme of the renin-angiotensin system that regula tes blood pressure and water-electrolyte balance. Renin gene expressio n is regulated in a tissue-specific and developmentally linked manner. Similarly, the expression of RE is controlled in a differentiation-li nked manner, Thus, to investigate whether RE is involved in the regula tion of renin gene expression, we examined the effects of RE on transc riptional activity of the mouse renin (Ren-1C) promoter. The Ren-1C pr omoter contains two transcriptionally important elements; the RU-1 (-2 24 to -138) and RP-2 (-75 to -47) elements. RE activated the Ren-IC pr omoter in human embryonic kidney cells. The promoter element responsib le for RE-mediated transcriptional regulation was the RP-2 element, Th e results of DNA-protein binding experiments showed that RE increased nuclear binding activity to the RP-2 element, and site-directed mutati on which disrupted binding of nuclear factors to the RP-2 element mark edly reduced RE-mediated activation of Ren-IC promoter in human embryo nic kidney cells. These results indicate that the RP-2 element plays a n important role in RE-mediated transcriptional regulation of Ren-IC p romoter activity in human embryonic kidney cells, thereby suggesting a n interesting mechanism by which RE may modulate the renin-angiotensin system.