Dynamic landscape of protein occupancy across the Escherichia coli chromosome

• Published in: PLoS biology Vol. 19; no. 6; p. e3001306
• Main Authors: Freddolino, Peter L, Amemiya, Haley M, Goss, Thomas J, Tavazoie, Saeed
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-06-2021; Public Library of Science (PLoS)
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Bacteria; Bacterial physiology; Binding sites; Biology and life sciences; Chromosomes; Chromosomes, Bacterial - metabolism; Coliforms; Deoxyribonucleic acid; Digital audio players; Display devices; DNA; DNA binding proteins; DNA-binding protein; DNA-Binding Proteins - metabolism; E coli; Environment; Environmental changes; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; Experiments; Gene expression; Genetic aspects; Genetic engineering; Genomes; Heterochromatin; Methods and Resources; Microbiological research; Occupancy; Perturbation; Physiology; Promoter Regions, Genetic - genetics; Protein Binding; Proteins; Research and Analysis Methods; RNA polymerase; Sigma Factor - metabolism; Statistical inference; Transcription factors; Transcription Factors - chemistry; Transcription Factors - metabolism; United States
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001306

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 resolution, 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.