Widespread strain-specific distinctions in chromosomal binding dynamics of a highly conserved Escherichia coli transcription factor

Bacterial gene regulation is governed by often hundreds of transcription factors (TF) 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 harbouring 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 “personalised” 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 analysed 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 occupancy 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 occupancy 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 intra-species distinctions in TF binding dynamics is a widespread phenomenon and represents “personalised” gene-regulatory potential.