  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 of sequenced regulatory architectures as well as to design novel
synthetic circuits. This work builds upon a beautiful recent experiment by
Urtecho et al. who measured the gene expression of over 10,000 promoters
spanning all possible combinations of a small set of regulatory elements. Using
this 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 refined
energy matrix model that incorporates this effect. We show that this the
refined energy matrix model can characterize the full suite of gene expression
data and explore several applications of this framework, namely, how
multivalent binding at the -35 and -10 sites can buffer 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.

Subcellular Processes