Dynamic landscape of protein occupancy across the Escherichia coli chromosome

Peter L. Freddolino, Haley M. Amemiya, Thomas J. Goss, Saeed Tavazoie, Matthew K. Waldor
2021 PLoS Biology  
Free-living bacteria adapt to environmental change by reprogramming gene expression through precise interactions of hundreds of DNA-binding proteins. A predictive understanding of bacterial physiology requires us to globally monitor all such protein–DNA interactions across a range of environmental and genetic perturbations. Here, we show that such global observations are possible using an optimized version of in vivo protein occupancy display technology (in vivo protein occupancy display—high
more » ... solution, IPOD-HR) and present a pilot application to Escherichia coli. We observe that the E. coli protein–DNA interactome organizes into 2 distinct prototypic features: (1) highly dynamic condition-dependent transcription factor (TF) occupancy; and (2) robust kilobase scale occupancy by nucleoid factors, forming silencing domains analogous to eukaryotic heterochromatin. We show that occupancy dynamics across a range of conditions can rapidly reveal the global transcriptional regulatory organization of a bacterium. Beyond discovery of previously hidden regulatory logic, we show that these observations can be utilized to computationally determine sequence specificity models for the majority of active TFs. Our study demonstrates that global observations of protein occupancy combined with statistical inference can rapidly and systematically reveal the transcriptional regulatory and structural features of a bacterial genome. This capacity is particularly crucial for non-model bacteria that are not amenable to routine genetic manipulation.
doi:10.1371/journal.pbio.3001306 pmid:34170902 pmcid:PMC8282354 fatcat:zft56u6r5jgpjeg4snejdejome