Renin gene expression: The switch and the fingers

1. Now that many of the factors and control elements that regulate renin transcription have been identified, the scene is set to address the question of the mode of control. 2. Based on current gene control theories, either renin gene transcription in each cell undergoes gradual responses over a continuous range or transcription is switched completely on or completely off. The latter model of 'binary' or 'variegated' expression fits with observations such as the 'recruitment' of new cells for renin expression during strong physiological stimulation and the progressive switching off of expression during development. 3. The renin gene offers an excellent general model for testing the mode of control of genes that are subject to continuous modulatory influences from the demands of physiological perturbations. This is because the promoter is well characterized and is subject to the influence of a strong far-upstream enhancer, one of the key elements of the variegation model. 4. Renin is also controlled at the post-transcriptional level and this, like transcriptional control, involves cAMP mechanisms. We have cloned the human and mouse homologues of a protein (ZNF265) that is important in renin mRNA processing and stability. This uses 'zinc fingers' to bind the mRNA. The role of this and other proteins in splicing and stabilization of mRNA is now being elucidated. 5. Unravelling the mechanisms that determine rate of supply of renin mRNA to the biosynthetic machinery is being assisted by advances in concepts and techniques in the rapidly moving field of genomics.