Widespread Strain-Specific Distinctions in Chromosomal Binding Dynamics of a Highly Conserved Escherichia coli...

Bacterial gene regulation is governed by often hundreds of transcription factors (TFs) that bind directly to targets on the chromosome. Global studies of TFs usually make assumptions that regulatory targets within model strains will be conserved between members of the same species harboring common genetic targets. We recently discovered that YhaJ of Escherichia coli is crucial for virulence in two different pathotypes but binds to distinct regions of their genomes and regulates no common genes. This surprising result leads to strain-specific mechanisms of virulence regulation, but the implications for other E. coli pathotypes or commensals were unclear. Here, we report that heterogenous binding of YhaJ is widespread within the E. coli species. We analyzed the global YhaJ binding dynamics of four evolutionarily distinct E. coli isolates under two conditions, revealing 78 significant sites on the core genome as well as horizontally acquired loci. Condition-dependent dosage of YhaJ correlated with the number of occupied sites in vivo but did not significantly alter its enrichment at regions bound in both conditions, explaining the availability of this TF to occupy accessory sites in response to the environment. Strikingly, only ∼15% of YhaJ binding sites were common to all strains. Furthermore, differences in enrichment of uncommon sites were observed largely in chromosomal regions found in all strains and not explained exclusively by binding to strain-specific horizontally acquired elements or mutations in the DNA binding sequence. This observation suggests that intraspecies distinctions in TF binding dynamics are a widespread phenomenon and represent strain-specific gene regulatory potential.IMPORTANCE In bacterial cells, hundreds of transcription factors coordinate gene regulation and thus are a major driver of cellular processes. However, the immense diversity in bacterial genome structure and content makes deciphering regulatory networks challenging. This is particularly apparent for the model organism Escherichia coli as evolution has driven the emergence of species members with highly distinct genomes, which occupy extremely different niches in nature. While it is well-known that transcription factors must integrate horizontally acquired DNA into the regulatory network of the cell, the extent of regulatory diversity beyond single model strains is unclear. We have explored this concept in four evolutionarily distinct E. coli strains and show that a highly conserved transcription factor displays unprecedented diversity in chromosomal binding sites. Importantly, this diversity is not restricted to strain-specific DNA or mutation in binding sites. This observation suggests that strain-specific regulatory networks are potentially widespread within individual bacterial species.