A Predictive Theory of Allosteric Regulation in Transcription*

Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model which applies to a variety of regulatory architectures. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model accurately captures the induction profiles of these strains and enables us to derive analytic expressions for key properties such as the dynamic range, [EC₅₀], and steepness of response. Finally, we derive an expression for the free energy of repressors which enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.