Multiscale Structuring of the E. coli Chromosome by Nucleoid-Associated and Condensin Proteins

As in eukaryotes, bacterial genomes are not randomly folded. Bacterial genetic information is generally carried on a circular chromosome with a single origin of replication from which two replication forks proceed bidirectionally toward the opposite terminus region. Here, we investigate the higher-order architecture of the Escherichia coli genome, showing its partition into two structurally distinct entities by a complex and intertwined network of contacts: the replication terminus (ter) region and the rest of the chromosome. Outside of ter, the condensin MukBEF and the ubiquitous nucleoid-associated protein (NAP) HU promote DNA contacts in the megabase range. Within ter, the MatP protein prevents MukBEF activity, and contacts are restricted to ∼280 kb, creating a domain with distinct structural properties. We also show how other NAPs contribute to nucleoid organization, such as H-NS, which restricts short-range interactions. Combined, these results reveal the contributions of major evolutionarily conserved proteins in a bacterial chromosome organization. [Display omitted] •Hi-C approach confirms the segmentation of the E. coli chromosome into macrodomains•The multilevel organization is mediated by ubiquitous nucleoid-associated proteins•Condensin and histone-like HU protein promote long-range contacts in chromosome arms•The protein MatP insulates the ter region from the structuring action of condensin Contacts within the E. coli chromosome effectively divide it into functionally distinct structural regions.