Repressors

Jacques Monod and Francois Jacob, our heroes, described a gene-regulatory world run exclusively by repressors. The activities of repressors, their abilities to bind DNA as we later learned, would be controlled — helped or hindered — by small molecules that bind these proteins. They showed [1] that networks of considerable complexity could be created with such a regulatory system. There was no need for gene ‘activators’ and, indeed, invoking such regulators (strongly resisted by Monod, it is said) would only confuse a coherent picture. This picture has been turned on its head. Almost all genes — especially in eukaryotes — are controlled My Word by the combined effects of activators and repressors. What happened? To get from there to here we need invoke two ideas, one implicit in the original picture of Monod and Jacob. It helps to start with bacteria to understand this predominant mode of gene regulation — control by both activators and repressors. First, without making a point of it, Monod and Jacob assumed that bacterial RNA polymerase is constitutively active — it will automatically, as it were, transcribe any gene whose promoter is accessible (not blocked by a repressor). Second, something the French scientists did not realize, promoters vary widely in their affinities for the active polymerase. One of the promoters they studied, from phage lambda, turns out to be exceptional: its affinity for polymerase is so high that control by repressor suffices: the gene is essentially ‘off’ in the presence of lambda repressor, which binds DNA and excludes polymerase; or it is fully ‘on’ (transcribed at a high rate) in the absence of repressor.