DNA-protein interactions in the regulation of gene expression
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In this paper we describe a number of approaches to the nature and specificity of DNA-protein interactions involved in the regulation of gene expression at the transcriptional level. We discuss primarily the binding of ‘single-specific-site’ regulatory proteins to DNA targets. This involves consideration of several aspects of the specificity of DNA-protein interactions, including: (1) the combinatorial specification of the number of base pairs required to define a unique binding site in a genome of given size; (2) the structure of DNA and protein binding sites, including structural complementarity and steric aspects; (3) the energetics of the binding interaction, including both specific and non-specific binding; (4) the thermodynamics and kinetics of the overall interaction, as determined by the net binding free energy of specific complex formation and the effects of competing sites; and (5) equilibrium binding selection, which determines the actual level of saturation of the specific (regulatory) target under various environmental conditions. These aspects are all interdependent, and a coherent picture of the specificity of such interactions can be obtained only by considering them all in context. Such an approach has been set forth by us previously, in part, in von Hippel and Berg (1986), and portions of this overview are taken directly from that treatment. In conclusion, we consider how these ideas modulate the evolutionary ‘design’ of regulatory proteins, as well as the formulation of purification procedures and binding assays for these proteins, and how these approaches may apply in vivo.
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