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

Connolly, J. P.R., O'Boyle, N. and Roe, A. J. (2020) Widespread strain-specific distinctions in chromosomal binding dynamics of a highly conserved Escherichia coli transcription factor. mBio, 11, e01058-20. (doi: 10.1128/mBio.01058-20) (PMID:32576674) (PMCID:PMC7315121)

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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.

Item Type:Articles
Additional Information:J.P.R.C. is supported by a fellowship from the Faculty of Medical Sciences (Newcastle University) and a Springboard award from the Academy of Medical Sciences [SBF005\1029]. N.O. is supported by a Tenovus Scotland small pilot grant. A.J.R. acknowledges support from the Biotechnology and Biological Sciences Research Council [BB/M029646/1, BB/R006539/1].
Glasgow Author(s) Enlighten ID:Connolly, Dr James and Roe, Professor Andrew and O Boyle, Dr Nicky
Authors: Connolly, J. P.R., O'Boyle, N., and Roe, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN (Online):2150-7511
Copyright Holders:Copyright © 2020 Connolly et al.
First Published:First published in mBio 11:e01058-20
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172251Where and Why: The Influence of Host Metabolism on Bacterial Niche SpecificityRichard CogdellBiotechnology and Biological Sciences Research Council (BBSRC)BB/M029646/1Institute of Infection, Immunity & Inflammation
300280The Role of Dietary D-serine in Health and DiseaseAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/R006539/1III - Bacteriology