Tuning transcriptional regulation through signaling: A predictive theory

14 Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that 15 directly link the experimentally tunable parameters of a system to its input-output response. To that end, 16 we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux 17 model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first 18 predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding 19 strengths and then constructing and measuring their response. Our model not only accurately captures 20 the induction profiles of these strains but also enables us to derive analytic expressions for key properties 21 such as the dynamic range and [EC50]. Finally, we derive an expression for the free energy of allosteric 22 repressors which enables us to collapse our experimental data onto a single master curve that captures 23 the diverse phenomenology of the induction profiles. 24