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

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.

[1]  D. Rudner,et al.  Recruitment of SMC by ParB-parS Organizes the Origin Region and Promotes Efficient Chromosome Segregation , 2009, Cell.

[2]  P. Cicuta,et al.  Short-time movement of E. coli chromosomal loci depends on coordinate and subcellular localization , 2013, Nature Communications.

[3]  O. Espéli,et al.  DNA dynamics vary according to macrodomain topography in the E. coli chromosome , 2008, Molecular microbiology.

[4]  O. Sliusarenko,et al.  High‐throughput, subpixel precision analysis of bacterial morphogenesis and intracellular spatio‐temporal dynamics , 2011, Molecular microbiology.

[5]  N. Kleckner,et al.  Chromosome and Replisome Dynamics in E. coli: Loss of Sister Cohesion Triggers Global Chromosome Movement and Mediates Chromosome Segregation , 2005, Cell.

[6]  F. Alber,et al.  Physical tethering and volume exclusion determine higher-order genome organization in budding yeast , 2012, Genome research.

[7]  Kurt Binder,et al.  Monte Carlo Simulation in Statistical Physics , 1992, Graduate Texts in Physics.

[8]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[9]  Andrew Wright,et al.  Entropy as the driver of chromosome segregation , 2010, Nature Reviews Microbiology.

[10]  Marc A Marti-Renom,et al.  The Three-dimensional Architecture of a Bacterial Genome and Its Alteration by Genetic Perturbation , 2022 .

[11]  Paul A. Wiggins,et al.  Mapping the driving forces of chromosome structure and segregation in Escherichia coli , 2013, Nucleic acids research.

[12]  A. Grossman,et al.  Movement of replicating DNA through a stationary replisome. , 2000, Molecular cell.

[13]  J. Sedat,et al.  Spatial partitioning of the regulatory landscape of the X-inactivation centre , 2012, Nature.

[14]  H. Stanley,et al.  Statistical physics of macromolecules , 1995 .

[15]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[16]  D. Sherratt,et al.  Independent Positioning and Action of Escherichia coli Replisomes in Live Cells , 2008, Cell.

[17]  A. Ishihama,et al.  Fundamental structural units of the Escherichia coli nucleoid revealed by atomic force microscopy. , 2004, Nucleic acids research.

[18]  S. Zimmerman,et al.  Shape and compaction of Escherichia coli nucleoids. , 2006, Journal of structural biology.

[19]  S. Jun,et al.  Entropy-driven spatial organization of highly confined polymers: Lessons for the bacterial chromosome , 2006, Proceedings of the National Academy of Sciences.

[20]  Kurt Binder,et al.  Monte Carlo Simulation in Statistical Physics , 1992, Graduate Texts in Physics.

[21]  M. Waldor,et al.  A dynamic, mitotic-like mechanism for bacterial chromosome segregation. , 2006, Genes & development.

[22]  F. Boccard,et al.  Chromosomal Organization and Segregation in Pseudomonas aeruginosa , 2013, PLoS genetics.

[23]  S. Adhya,et al.  Architectural organization in E. coli nucleoid. , 2012, Biochimica et biophysica acta.

[24]  Paul A. Wiggins,et al.  Strong intranucleoid interactions organize the Escherichia coli chromosome into a nucleoid filament , 2010, Proceedings of the National Academy of Sciences.

[25]  Jan-Willem Veening,et al.  SMC is recruited to oriC by ParB and promotes chromosome segregation in Streptococcus pneumoniae , 2011, Molecular microbiology.

[26]  Martin A. White,et al.  Non-random segregation of sister chromosomes in Escherichia coli , 2008, Nature.

[27]  Marc A. Martí-Renom,et al.  The Three-Dimensional Architecture of a Bacterial Genome and Its Alteration by Genetic Perturbation , 2012, RECOMB.

[28]  Reid C. Johnson,et al.  Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions , 2012, Molecular microbiology.

[29]  D. Sherratt,et al.  Modulation of Escherichia coli sister chromosome cohesion by topoisomerase IV. , 2008, Genes & development.

[30]  M. Rossignol,et al.  Macrodomain organization of the Escherichia coli chromosome , 2004, The EMBO journal.

[31]  A. Grossman,et al.  The extrusion-capture model for chromosome partitioning in bacteria. , 2001, Genes & development.

[32]  Christian Lesterlin,et al.  Sister chromatid interactions in bacteria revealed by a site‐specific recombination assay , 2012, The EMBO journal.

[33]  D. Sherratt,et al.  MukB colocalizes with the oriC region and is required for organization of the two Escherichia coli chromosome arms into separate cell halves , 2007, Molecular microbiology.

[34]  F. Hansen,et al.  Progressive segregation of the Escherichia coli chromosome , 2006, Molecular microbiology.

[35]  Jesse R. Dixon,et al.  Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions , 2012, Nature.

[36]  S. Doniach.  Biological Physics: Energy, Information, Life , 2003 .

[37]  S. Jun,et al.  Intrachain Ordering and Segregation of Polymers under Confinement , 2012 .

[38]  Adrian H. Elcock,et al.  Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm , 2010, PLoS Comput. Biol..

[39]  J. Errington,et al.  Recruitment of Condensin to Replication Origin Regions by ParB/SpoOJ Promotes Chromosome Segregation in B. subtilis , 2009, Cell.

[40]  Christophe Zimmer,et al.  A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus , 2012, Current Biology.

[41]  Ludovic Le Chat,et al.  Let's get ‘Fisical’ with bacterial nucleoid , 2012, Molecular microbiology.

[42]  Stéphane Robin,et al.  The MatP/matS Site-Specific System Organizes the Terminus Region of the E. coli Chromosome into a Macrodomain , 2008, Cell.

[43]  M. Radosavljevic,et al.  Biological Physics: Energy, Information, Life , 2003 .

[44]  Kevin D Dorfman,et al.  Physical descriptions of the bacterial nucleoid at large scales, and their biological implications , 2012, Reports on progress in physics. Physical Society.

[45]  Hawoong Jeong,et al.  Ring polymers as model bacterial chromosomes: confinement, chain topology, single chain statistics, and how they interact , 2012 .

[46]  Nancy Kleckner,et al.  Four-Dimensional Imaging of E. coli Nucleoid Organization and Dynamics in Living Cells , 2013, Cell.

[47]  Dieter W. Heermann,et al.  A model for Escherichia coli chromosome packaging supports transcription factor-induced DNA domain formation , 2011, Nucleic acids research.

[48]  N. Cozzarelli,et al.  Closing the ring: links between SMC proteins and chromosome partitioning, condensation, and supercoiling. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[49]  N. Kleckner,et al.  Escherichia coli sister chromosome separation includes an abrupt global transition with concomitant release of late-splitting intersister snaps , 2011, Proceedings of the National Academy of Sciences.

[50]  G. Jagura-Burdzy,et al.  Bacterial chromosome segregation , 2005 .

[51]  O. Espéli,et al.  A MatP–divisome interaction coordinates chromosome segregation with cell division in E. coli , 2012, The EMBO journal.

[52]  L. Shapiro,et al.  A spindle-like apparatus guides bacterial chromosome segregation , 2010, Nature Cell Biology.

[53]  T. Odijk,et al.  Osmotic compaction of supercoiled DNA into a bacterial nucleoid. , 1998, Biophysical chemistry.

[54]  D. Sherratt,et al.  The two Escherichia coli chromosome arms locate to separate cell halves. , 2006, Genes & development.

[55]  Davide Marenduzzo,et al.  Entropic organization of interphase chromosomes , 2009, The Journal of cell biology.

[56]  Acknowledgements , 1992, Experimental Gerontology.

[57]  D. Sherratt,et al.  Chromosome replication and segregation in bacteria. , 2012, Annual review of genetics.

[58]  M. Schumacher,et al.  Molecular basis for a protein-mediated DNA-bridging mechanism that functions in condensation of the E. coli chromosome. , 2012, Molecular cell.

[59]  Patrick T. McGrath,et al.  Rapid and sequential movement of individual chromosomal loci to specific subcellular locations during bacterial DNA replication. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Charles J. Dorman,et al.  Genome architecture and global gene regulation in bacteria: making progress towards a unified model? , 2013, Nature Reviews Microbiology.

[61]  William J. Godinez,et al.  Chromosome segregation by the Escherichia coli Min system , 2013, Molecular systems biology.

[62]  Gilles Charvin,et al.  Stretching of macromolecules and proteins , 2003 .

[63]  Mark Goulian,et al.  Membrane protein expression triggers chromosomal locus repositioning in bacteria , 2012, Proceedings of the National Academy of Sciences.

[64]  D. Rudner,et al.  Organization and segregation of bacterial chromosomes , 2013, Nature Reviews Genetics.