Regulation of transcription: from lambda to eukaryotes Mark Ptashne  Trends in Biochemical Sciences  Volume 30, Issue 6, Pages 275-279 (June 2005) DOI: 10.1016/j.tibs.2005.04.003 Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 1 Cooperative binding of proteins to DNA. Simple binding reactions such as those shown here underlie many aspects of gene regulation and regulation of other biologically important processes. (a) The binding sites for proteins 1 and 2 are adjacent on DNA. When protein 1 or 2 is present alone, a series of snapshots would show the corresponding DNA site to be occupied only rarely – say 1% of the time. But when both proteins are present, the DNA sites are occupied more often – say 99% of the time. The effect only requires that the proteins touch one another, and weakly at that. A ‘helping’ (cooperative) effect of even tenfold, which requires only a one or two kcal of interaction energy, can be biologically crucial. Cooperativity (recruitment) requires that the interacting proteins be present below a specified level: an increase in the concentration of protein 1 or 2 would enable that protein to bind substantially without help from its partner. If protein 2 was RNA polymerase, protein 1 would be called an ‘activator’ of transcription. There are many variations and elaborations of the reaction depicted in (a). Sometimes many proteins interact and bind cooperatively, and sometimes the sites to which they bind are widely separated as in (b). In this case, the DNA must loop to accommodate the binding reaction. (c) DNA looping caused by cooperative binding of proteins 1 and 2 brings together sites 3 and 4, and this enables the more weakly binding proteins 3 and 4 to bind cooperatively. Examples of each of these reactions are found in lambda. Trends in Biochemical Sciences 2005 30, 275-279DOI: (10.1016/j.tibs.2005.04.003) Copyright © 2005 Elsevier Ltd Terms and Conditions