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Physical constraints and functional characteristics of transcription factorâDNA interactionProceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 19. (17 September 2002), pp. 12015-12020.
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Abstract10.1073/pnas.192693599 We study theoretical âdesign principlesâ for transcription factor (TF)âDNA interaction in bacteria, focusing particularly on the statistical interaction of the TFs with the genomic background (i.e., the genome without the target sites). We introduce and motivate the concept of programmability, i.e., the ability to set the threshold concentration for TF binding over a wide range merely by mutating the binding sequence of a target site. This functional demand, together with physical constraints arising from the thermodynamics and kinetics of TFâDNA interaction, leads us to a narrow range of âoptimalâ interaction parameters. We find that this parameter set agrees well with experimental data for the interaction parameters of a few exemplary prokaryotic TFs, which indicates that TFâDNA interaction is indeed programmable. We suggest further experiments to test whether this is a general feature for a large class of TFs.
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