Polymer modeling of the E. coli genome reveals the involvement of locus positioning and macrodomain structuring for the control of chromosome conformation and segregation

Abstract

The mechanisms that control chromosome conformation and segregation in bacteria have not yet been elucidated. In Escherichia coli, the mere presence of an active process remains an open question. Here, we investigate the conformation and segregation pattern of the E. coli genome by performing numerical simulations on a polymer model of the chromosome. We analyze the roles of the intrinsic structuring of chromosomes and the forced localization of specific loci, which are observed in vivo. Specifically, we examine the segregation pattern of a chromosome that is divided into four structured macrodomains (MDs) and two non-structured regions. We find that strong osmotic-like organizational forces, which stem from the differential condensation levels of the chromosome regions, dictate the cellular disposition of the chromosome. Strikingly, the comparison of our in silico results with fluorescent imaging of the chromosome choreography in vivo reveals that in the presence of MDs the targeting of the origin and terminus regions to specific positions are sufficient to generate a segregation pattern that is indistinguishable from experimentally observed patterns.

Persistent super-diffusive motion of Escherichia coli chromosomal loci

“…Decondensation rapid movements might explain the specificity of the Ter region ( Supplementary Fig. 8), which is reported to be more fluid and localized at the nucleoid periphery 29,30 (this happens far from cell divisions, when the Ter region is instead condensed and tethered 25,28,31 ). In the hypothesis of decondensation, loci that are freed from some chromosomal constraints might perform a faster random motion in the cytoplasm, but their trajectories could be persistent enough to be mistaken for near-ballistic at the observation timescale.…”

Polymer segregation under confinement: Free energy calculations and segregation dynamics simulations

“…Notably, it has been proposed to be the dominant mechanism for chromosome separation in bacteria, with proteins identified as segregation factors serving mainly to create the right conditions for entropy-driven segregation. [4][5][6] While several recent studies have challenged this view, [7][8][9][10][11] an understanding of bacterial chromosome separation remains elusive and the importance of entropy as a driving force is currently not clear. 12,13 Computer simulation studies have provided insight into the segregation of polymers under confinement.…”

Dynamic Organization: Chromosome Domains in <b><i>Escherichia coli</i></b>

“…However, data of in vivo analysis of chromosome organization, dynamics and segregation did not fit well with pure entropic forces [Benza et al, 2012;Di Ventura et al, 2013;Fisher et al, 2013;Hadizadeh Yazdi et al, 2012;Le Chat and Espéli, 2012]. Additionally, recent numerical simulations show that entropy alone is not sufficient to generate the experimentally observed chromosome disposition [Junier et al, 2014]. But strikingly, taking into account few structure elements like the macrodomains and specifically placed origin and terminus positions in the polymer model leads to segregation pattern predictions similar to those observed in vivo [Junier et al, 2014].…”

“…Additionally, recent numerical simulations show that entropy alone is not sufficient to generate the experimentally observed chromosome disposition [Junier et al, 2014]. But strikingly, taking into account few structure elements like the macrodomains and specifically placed origin and terminus positions in the polymer model leads to segregation pattern predictions similar to those observed in vivo [Junier et al, 2014].…”