Renin Regulation

Kidney International (1994) 46, 1516–1521; doi:10.1038/ki.1994.434

Function of human renin proximal promoter DNA

Brian J Morris, D Lynne Smith, Ronald E Law, Yung S Do, Kathy J Shaw and Willa A Hsueh

Molecular Biology & Hypertension Laboratory, Department of Physiology, The University of Sydney, New South Wales, Australia, and SCOR Laboratory, Department of Medicine, University of Southern California School of Medicine, Los Angeles, California, USA

Correspondence: Brian J Morris DSc, Molecular Biology & Hypertension Laboratory, Department of Physiology, Building F13, The University of Sydney, New South Wales 2006, Australia.

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Abstract

Function of human renin proximal promoter DNA. An understanding of the mechanisms involved in the control of the human renin promoter have been hampered and confounded in work to date because of deficiencies in material available and experimental design. The promoter appears to be weak and a good cell model is lacking. Chorio-decidual cultures have been used since these have high renin synthesis, are readily available and grow well in culture. They suffer, however, from phenotypic variability and do not transfect well in transient expression analyses. Recent evidence suggests that 2.6 kb of proximal 5'-flanking DNA is unable to induce native promoter activity under basal conditions. Experiments in which an exogenous enhancer was introduced have raised the possibility that an endogenous enhancer residing outside of the 2.6 kb 5'-flanking region could be required. Cell-type specific factors also appear to be needed. The proximal flanking DNA does, however, appear to be capable of conferring activity on the promoter in chorio-decidual cells under stimulated conditions, suggesting that factors so activated may have considerable importance. Evidence suggests that forskolin-responsive signal transduction pathways may lead cyclic AMP responsive element (CRE) binding protein (CREB) to act on a CRE at -222 in the proximal REN promoter DNA. Activation of the mouse promoter by cAMP appears to involve a different element, however. Furthermore, overall control of renin synthesis is likely to involve post-transcriptional mechanisms as well. Thus, despite being the first cardiovascular gene to be cloned, much more work is required before the control of the human renin gene is fully understood.

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