Hi-C embedded polymer model of<i>Escherichia coli</i>reveals the origin of heterogeneous subdiffusion in chromosomal loci

Bera, Palash; Wasim, Abdul; Mondal, Jagannath

doi:10.1103/physreve.105.064402

Cited by 11 publications

(13 citation statements)

References 87 publications

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“…We also note that the Hi-C interactions which have been integrated in the current model have been identified to be instrumental in predicting the heterogeneous loci dynamics observed in E. coli. 58−60 In a previous study from our group, 61 which used a relatively lower resolution model (5000 bp resolution) but retained Hi-C derived interactions, was found to provide excellent corroboration with the loci dynamics of the E. coli chromosome. We finally had shown that Hi-C contacts embedded into the polymer model were the root cause for the model being able to capture the heterogeneous loci dynamics observed in experiments.…”

Section: Discussionmentioning

confidence: 91%

Development of a Data-Driven Integrative Model of a Bacterial Chromosome

Wasim

Bera

Mondal

2023

J. Chem. Theory Comput.

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The chromosome of archetypal bacteria E. coli is known for a complex topology with a 4.6 × 10 6 base pairs (bp) long sequence of nucleotides packed within a micrometer-sized cellular confinement. The inherent organization underlying this chromosome eludes general consensus due to the lack of a high-resolution picture of its conformation. Here we present our development of an integrative model of E. coli at a 500 bp resolution (https://github.com/JMLab-tifrh/ecoli_finer), which optimally combines a set of multiresolution genome-wide experimentally measured data within a framework of polymer based architecture. In particular the model is informed with an intragenome contact probability map at 5000 bp resolution derived via the Hi-C experiment and RNA-sequencing data at 500 bp resolution. Via dynamical simulations, this data-driven polymer based model generates an appropriate conformational ensemble commensurate with chromosome architectures that E. coli adopts. As a key hallmark of the E. coli chromosome the model spontaneously self-organizes into a set of nonoverlapping macrodomains and suitably locates plectonemic loops near the cell membrane. As novel extensions, it predicts a contact probability map simulated at a higher resolution than precedent experiments and can demonstrate segregation of chromosomes in a partially replicating cell. Finally, the modular nature of the model helps us devise control simulations to quantify the individual role of key features in hierarchical organization of the bacterial chromosome.

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Section: Discussionmentioning

confidence: 91%

Development of a Data-Driven Integrative Model of a Bacterial Chromosome

Wasim

Bera

Mondal

2023

J. Chem. Theory Comput.

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“…By explicitly modeling motors that may bind the polymer and apply forces, the possibility of a super-diffusive regime in the intermediate time scales has been discussed [86]. Using locus-specific effective temperatures has been yet another approach to recapitulate nonequilibrium aspects [87,88], however, the possibility of super-diffusion is not within the scope of such approaches. Phenomenological modeling of active forces with hydrodynamics has been useful in understanding coherent motions in the genome [53,89].…”

Section: Discussionmentioning

confidence: 99%

Temporally correlated active forces drive segregation and enhanced dynamics in chromosome polymers

Brahmachari

Markovich

MacKintosh

et al. 2023

Preprint

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Understanding the mechanisms governing the structure and dynamics of flexible polymers like chromosomes, especially, the signatures of motor-driven active processes is of great interest in genome biology. We study chromosomes as a coarse-grained polymer model where microscopic motor activity is captured via an additive temporally persistent noise. The active steady state is characterized by two parameters: active force, controlling the persistent-noise amplitude, and correlation time, the decay time of active noise. We find that activity drives dynamic compaction, leading to a globally collapsed entangled globule for long correlation times. Diminished topological constraints destabilize the entangled globule, and the polymer segments trapped in the globule move toward the periphery, resulting in an enriched density near the periphery. We also show that heterogeneous activity may lead to the segregation of the highly dynamic species from the less dynamic one. Our model suggests correlated motor forces as a factor (re)organizing chromosome compartments and driving transcriptionally active regions towards the chromosome periphery. This contrasts the passive adhesive or repulsive forces shaping chromosome structures. Importantly, structural ensembles are not sufficient to distinguish between the active or passive mechanisms, but the dynamics may hold key distinguishing signatures. The motor-driven polymer shows distinctive dynamic features like enhanced apparent diffusivity and exploration of all the dynamic regimes (sub-diffusion, effective diffusion, and super-diffusion) at various lag times.

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“…The mass, diameter, and the details modeling aspect of each component are given in SI(Table-S1). We mapped the reduced unit of simulation to the physical units by taking the real value of the diameter of each DNA bead (σ = 67.31 nm) [34], temperature (T = 303K), and viscosity of the cytoplasm (η = 17.5P a.s) [38,39]. In real physical unit the value of τ B becomes 3πησ 3 k B T ≈ 12s.…”

Section: Model and Methodmentioning

confidence: 99%

“…The Hi-C-derived inter-genomic contacts are modeled as harmonic springs with probability-dependent distance and distance-dependent force constants (see SI method section). Unlike our previous model [33, 34], in our current study, we have incorporated polysome and ribosomes. Each 30S, 50S, and 70S ribosomal sub-units have been modeled as spherical particles with different diameters ( σ 30 S = 14 nm, σ 50 S = 17 nm, and σ 70 S = 20 nm) and each polysome is modeled by 13-mer of 70S ribosomal sub-units which behave like a freely jointed chain.…”

Section: Methodsmentioning

confidence: 99%

Protein Translation Can Fluidize Bacterial Cytoplasm

Bera,

Wasim,

Bakshi

et al. 2024

Preprint

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The cytoplasm of bacterial cells is densely packed with highly polydisperse macromolecules that exhibit glassy dynamics. Research has revealed that metabolic activities in living cells can counteract the glassy nature of these macromolecules, allowing the cell to maintain critical fluidity for its growth and function. While it has been proposed that the crowded cytoplasm is responsible for this glassy behavior, a detailed explanation for how cellular activity induces fluidization remains elusive. In this study, we introduce and validate a novel hypothesis through computer simulations: protein synthesis in living cells contributes to the metabolism-dependent fluidization of the cytoplasm. The main protein synthesis machinery, ribosomes, frequently shift between fast and slow diffusive states. These states correspond to the independent movement of ribosomal subunits and the actively translating ribosome chains called polysomes, respectively. Our simulations demonstrate that the frequent transitions of the numerous ribosomes, which constitute a significant portion of the cell proteome, greatly enhance the mobility of other macromolecules within the bacterial cytoplasm. Considering that ribosomal protein synthesis is the largest consumer of ATP in growing bacterial cells, the translation process likely serves as the primary mechanism for fluidizing the cytoplasm in metabolically active cells.

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Hi-C embedded polymer model ofEscherichia colireveals the origin of heterogeneous subdiffusion in chromosomal loci

Cited by 11 publications

References 87 publications

Development of a Data-Driven Integrative Model of a Bacterial Chromosome

Development of a Data-Driven Integrative Model of a Bacterial Chromosome

Temporally correlated active forces drive segregation and enhanced dynamics in chromosome polymers

Protein Translation Can Fluidize Bacterial Cytoplasm

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