# How the Avidity of Polymerase Binding to the -35/-10 Promoter Sites Affects Gene Expression

## TL;DR

This paper introduces a refined energy matrix model that incorporates avidity effects between -35 and -10 promoter sites, improving predictions of gene expression and revealing how multivalent binding influences transcription regulation.

## Contribution

It demonstrates that avidity between promoter sites is essential for accurate gene expression modeling, challenging the assumption of independent additive effects in previous models.

## Key findings

- Avidity significantly affects RNA polymerase binding and gene expression.
- The refined model accurately predicts expression across diverse promoter sequences.
- Multivalent binding buffers against mutations and can inhibit expression when too tight.

## Abstract

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.