Negative control at a distance mediates catabolite repression in yeast

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Abstract
In prokaryotic organisms, the control of gene expression is mediated by regulatory proteins that activate or repress transcription1,2. However, the molecular mechanisms of positive and negative control are different. In terms of negative control, represser proteins bind to sites located within the promoter region and as a consequence sterically interfere with functional binding by RNA polymerase. Here, I examine the properties of a regulatory sequence that specifies catabolite (glucose) repression in the yeast Saccharomyces cerevisiae. Specifically, a DNA segment containing this regulatory site was fused upstream of the intact his3 promoter region and structural gene at several locations. Normally, his3 expression in these derivatives occurs at a basal level which can be induced by conditions of amino-acid starvation. However, in glucose medium, the catabolite regulatory sequence overrides the normal his3 promoter elements and reduces transcription both in normal and starvation conditions. The implication from these results is that in contrast to catabolite repression in Escherichia coli, which is mediated by catabolite-activating protein (CAP)3, catabolite repression in yeast occurs by a negative control mechanism involving a putative represser protein. The observation that this regulatory site exerts its repressing effects even when located upstream of an intact promoter region suggests that repression in yeast is not mediated by steric interference between regulatory proteins and the transcriptional apparatus.