Structuring a bacterial chromosome

Paul Wiggins
Whitehead Institute for Biomedical Research, Cambridge

The bacterial chromosome is condensed into a compact DNA-protein complex called the nucleoid. It is the nucleoid, not naked DNA, which is the substrate for all genetic processes from gene expression and DNA repair to chromosome replication. The physical structure of chromosomes has functional consequences: It affects gene regulation from the simplest prokaryotes to multicellular organisms. Nucleoid organization also plays a poorly understood yet central role in chromosome segregation. In spite of its biological significance, little is known about the mechanisms that physically organize the chromosome on a cellular-scale. In this talk I will describe work that combines biophysics with more traditional genetics and cell biology techniques to probe the mechanisms of nucleoid organization.

In spite of the common assumption that the interphase chromosome is well-modeled by an unstructured polymer, measurements of the locus positions reveal that the E.coli chromosome is precisely organized into a filament with a linear order. The vast majority of genetic loci are positioned in the cell with a precision of 10% of the cell length, with the exception of loci close to the replication terminus. The measured dependence of the precision of inter-locus distance on genomic distance singles out intra-nucleoid interactions as the mechanism responsible for chromosome organization. From the magnitude of this variance, we infer the existence of an as-yet uncharacterized higher-order DNA organization in bacteria. We demonstrate that both the stochastic and average structure of the nucleoid is captured by a fluctuating elastic filament model. The analysis of mutant strains reveals that the poorly structured terminus region plays a central but unexpected role in the organization of the entire nucleoid filament.