| Abstrakt: |
Although the key promoter elements necessary to drive transcription in Escherichia coli have long been understood, we still cannot predict the behavior of arbitrary novel promoters, hampering our ability to characterize the myriad sequenced regulatory architectures as well as to design new synthetic circuits. This work builds upon a beautiful recent experiment by Urtecho et al. [G. Urtecho, et al., Biochemistry, 68, 1539-1551 (2019)] who measured the gene expression of over 10,000 promoters spanning all possible combinations of a small set of regulatory elements. Using these data, we demonstrate that a central claim in energy matrix models of gene expression--that each promoter element contributes independently and additively to gene expression--contradicts experimental measurements. We propose that a key missing ingredient from such models is the avidity between the -35 and -10 RNA polymerase binding sites and develop what we call a multivalent model that incorporates this effect and can successfully characterize the full suite of gene expression data. We explore several applications of this framework, namely, how multivalent binding at the -35 and -10 sites can buffer RNA polymerase (RNAP) kinetics against mutations and how promoters that bind overly tightly to RNA polymerase can inhibit gene expression. The success of our approach suggests that avidity represents a key physical principle governing the interaction of RNA polymerase to its promoter. [ABSTRACT FROM AUTHOR] |
