Interconnecting solvent quality, transcription, and chromosome folding in Escherichia coli

• Published in: Cell 2021-07, Vol.184 (14), p.3626-3642.e14
• Main Authors: Xiang, Yingjie, Surovtsev, Ivan V., Chang, Yunjie, Govers, Sander K., Parry, Bradley R., Liu, Jun, Jacobs-Wagner, Christine
• Format: Article
• Language: English
• Subjects: Aminoglycosides - pharmacology; chromosome compaction; chromosome folding; Chromosomes, Bacterial - chemistry; Computer Simulation; Diffusion; DNA mesh size; DNA, Bacterial - chemistry; domain organization; Escherichia coli - drug effects; Escherichia coli - metabolism; Green Fluorescent Proteins - metabolism; Nucleic Acid Conformation; nucleoid; Particle Size; ribosome localization; Ribosomes - metabolism; Ribosomes - ultrastructure; RNA; RNA, Bacterial - metabolism; solvent quality; Solvents - chemistry; Transcription, Genetic - drug effects
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2021.05.037

All cells fold their genomes, including bacterial cells, where the chromosome is compacted into a domain-organized meshwork called the nucleoid. How compaction and domain organization arise is not fully understood. Here, we describe a method to estimate the average mesh size of the nucleoid in Escherichia coli. Using nucleoid mesh size and DNA concentration estimates, we find that the cytoplasm behaves as a poor solvent for the chromosome when the cell is considered as a simple semidilute polymer solution. Monte Carlo simulations suggest that a poor solvent leads to chromosome compaction and DNA density heterogeneity (i.e., domain formation) at physiological DNA concentration. Fluorescence microscopy reveals that the heterogeneous DNA density negatively correlates with ribosome density within the nucleoid, consistent with cryoelectron tomography data. Drug experiments, together with past observations, suggest the hypothesis that RNAs contribute to the poor solvent effects, connecting chromosome compaction and domain formation to transcription and intracellular organization. [Display omitted] •The apparent average mesh size of the Escherichia coli chromosome is around 50 nm•The cytoplasm effectively acts as a poor solvent for the chromosome•Ribosome and DNA densities are negatively correlated within the nucleoid region•RNA/DNA segregation is associated with chromosome compaction Measurements of nucleoid mesh size and DNA concentration reveal that the cytoplasm effectively behaves as a poor solvent for the chromosome, leading to chromosome compaction, DNA density heterogeneity, and spatial density of ribosomes that is negatively correlated with DNA density within the nucleoid. Transcription may contribute to the effective poor solvent quality of the cytoplasm.