Quantitative Dissection of a Bacterial Promoter: Cooperativity, Sensitivity, and Combinatorial Control

\textit{E. coli's lac} promoter offers a possibility of confronting system-level properties of transcriptional regulation with the known biochemistry of the molecular constituents and their mutual interactions. We repeated a previous study [Setty et al, PNAS 100: 7702-7 (2003)] by removing several extraneous factors which modulated expression of the \textit{lac} promoter. Through characterization of the promoter activity for key mutants and using thermodynamic modeling, we account for the control of the \textit{lac} promoter in terms of known interactions. We reveal how the sensitive response to inducers arises from the accumulation of several weakly cooperative interactions, and depict how the activator CRP plays a dual role as the enhancer and sensitizer of repression by assisting LacI-mediated DNA looping.