A segregative phase separation scenario of the formation of the bacterial nucleoid

Joyeux, Marc

doi:10.1039/c8sm01205a

Cited by 22 publications

(40 citation statements)

References 79 publications

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“…2). As was already observed in previous studies based on somewhat different models (32,33), demixing increases strongly close to the jamming threshold for spherical crowders ( 0.65…”

Section: The Effect On Dna Compaction Of Each Mechanism Taken Separatelysupporting

confidence: 86%

“…S2, which shows the evolution of R < > with ρ for torsionally relaxed DNA. A further slight increase of ρ beyond 0.65 will probably result in significantly stronger compaction of the DNA coil, as in (32,33), but the dynamics of the system becomes too slow to be numerically tractable with our computer facility.…”

Section: ρ ≈mentioning

confidence: 99%

“…In order to shed light on the interplay of DNA demixing and supercoiling, a coarsegrained model was developed along the same lines as those used previously to investigate facilitated diffusion (79)(80)(81), the interactions of DNA and H-NS nucleoid proteins (82)(83)(84), and the formation of the bacterial nucleoid (4,5,32,33,85). Torsional energy was accounted for in the model as described in (86) and the properties of the full model were investigated for different values of the number of crowders and the superhelical density (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…DNA-crowder and crowder-crowder interactions are expressed as sums of Debye-Hückel potentials, so that all components of the systems repel each other. It was shown previously(32,33) that maximum compaction of torsionally relaxed DNA chains is obtained when ρ, the effective crowder volume fraction (Eq. (S6)), is close to the jamming threshold for hard spheres, that is0.65 ρ ≈ The properties of the present model for supercoiled DNA were investigated by integrating numerically overdamped Langevin equations with time steps of 10 ps for different values of the number of crowders, N, and the superhelical density of the DNA chain, σ.…”

mentioning

confidence: 99%

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Bacterial Nucleoid: Interplay of DNA Demixing and Supercoiling

Joyeux

2020

Biophysical Journal

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Running title: DNA demixing and supercoiling.Abstract: This work addresses the question of the interplay of DNA demixing and supercoiling in bacterial cells. Demixing of DNA from other globular macromolecules results from the overall repulsion between all components of the system and leads to the formation of the nucleoid, which is the region of the cell that contains the genomic DNA in a rather compact form. Supercoiling describes the coiling of the axis of the DNA double helix to accommodate the torsional stress injected in the molecule by topoisomerases. Supercoiling is able to induce some compaction of the bacterial DNA, although to a lesser extent than demixing. In this paper, we investigate the interplay of these two mechanisms, with the goal of determining whether the total compaction ratio of the DNA is the mere sum or some more complex function of the compaction ratios due to each mechanism. To this end, we developed a coarse-grained bead-and-spring model and investigated its properties through Brownian dynamics simulations. This work reveals that there actually exist different regimes, depending on the crowder volume ratio and the DNA superhelical density. In particular, a regime where the effects of DNA demixing and supercoiling on the compaction of the DNA coil simply add up is shown to exist up to moderate values of the superhelical density. In contrast, the mean radius of the DNA coil no longer decreases above this threshold and may even increase again for sufficiently large crowder concentrations. Finally, the model predicts that the DNA coil may depart from the spherical geometry very close to the jamming threshold, as a trade-off between the need to minimize both the bending energy of the stiff plectonemes and the volume of the DNA coil to accommodate demixing.(#) marc.joyeux@univ-grenoble-alpes.fr Statement of significance: Many biological processes take place simultaneously in living cells. It is tempting to study each of them separately and rely on the hypothesis that cells behave like the "addition" of the isolated parts. This is however not always the case and the present work illustrates this fact. We consider two different processes, which are both able to compact the bacterial DNA, namely demixing and supercoiling, and we study how the DNA reacts when subject to both of them simultaneously. Through coarse-grained modeling and Brownian dynamics simulations, we show that the two processes are "additive" only in a limited range of biologically relevant values of the parameters and that their interplay is much more complex outside from this range.

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“…2). As was already observed in previous studies based on somewhat different models (32,33), demixing increases strongly close to the jamming threshold for spherical crowders ( 0.65…”

Section: The Effect On Dna Compaction Of Each Mechanism Taken Separatelysupporting

confidence: 86%

Section: ρ ≈mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Bacterial Nucleoid: Interplay of DNA Demixing and Supercoiling

Joyeux

2020

Biophysical Journal

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“…While all the above processes have been extensively studied, none of them appear to be capable of explaining the extent of the compaction needed to confine DNA into the experimentally observed nucleoid sizes. A number of theoretical (Odijk, 1998) and modeling studies (Mondal et al, 2011, Shendruk et al, 2015, Shin et al, 2014, Kim et al, 2015, Joyeux, 2018 have pointed out the importance of macromolecular crowders on the compaction of chromosomal DNA. In the seminal work, Odijk proposed that crowders and DNA separate into two distinct phases in an E. coli cell, a nucleoid and cytosolic phase (Odijk, 1998).…”

Section: Introductionmentioning

confidence: 99%

The effects of polydisperse crowders on the compaction of the Escherichia coli nucleoid

Yang

Männik

Retterer

et al. 2019

Preprint

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DNA binding proteins, supercoiling, macromolecular crowders, and transient DNA attachments to the cell membrane have all been implicated in the organization of the bacterial chromosome. However, it is unclear what role these factors play in compacting the bacterial DNA into a distinct organelle-like entity, the nucleoid. By analyzing the effects of osmotic shock and mechanical squeezing on Escherichia coli, we show that macromolecular crowders play a dominant role in the compaction of the DNA into the nucleoid. We find that a 30% increase in the crowder concentration from physiological levels leads to a 3-fold decrease in the nucleoid's volume. The compaction is anisotropic, being higher along the long axes of the cell at low crowding levels. At higher crowding levels the compression becomes isotropic, implying that E. coli nucleoids lack a well-defined backbone. We furthermore show that the compressibility of the nucleoid is not significantly affected by cell growth rates and by prior treatment with rifampicin. The latter results point out that in addition to poly-ribosomes, soluble cytoplasmic proteins have a significant contribution in determining the size of the nucleoid.

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Requirements for DNA-Bridging Proteins to Act as Topological Barriers of the Bacterial Genome

Joyeux

Junier

2020

Biophysical Journal

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Bacterial genomes have been shown to be partitioned into several-kilobase-long chromosomal domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbors. Both in vivo and in vitro experiments have been performed to question the nature of the topological barriers at play, leading to several predictions on possible molecular actors. Here, we address the question of topological barriers using polymer models of supercoiled DNA chains that are constrained such as to mimic the action of predicted molecular actors. More specifically, we determine under which conditions DNA-bridging proteins may act as topological barriers. To this end, we developed a coarse-grained bead-and-spring model and investigated its properties through Brownian dynamics simulations. As a result, we find that DNA-bridging proteins must exert rather strong constraints on their binding sites; they must block the diffusion of the excess of twist through the two binding sites on the DNA molecule and, simultaneously, prevent the rotation of one DNA segment relative to the other one. Importantly, not all DNA-bridging proteins satisfy this second condition. For example, single bridges formed by proteins that bind DNA nonspecifically, like H-NS dimers, are expected to fail with this respect. Our findings might also explain, in the case of specific DNA-bridging proteins like LacI, why multiple bridges are required to create stable independent topological domains. Strikingly, when the relative rotation of the DNA segments is not prevented, relaxation results in complex intrication of the two domains. Moreover, although the value of the torsional stress in each domain may vary, their differential is preserved. Our work also predicts that nucleoid-associated proteins known to wrap DNA must form higher protein-DNA complexes to efficiently work as topological barriers.

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A segregative phase separation scenario of the formation of the bacterial nucleoid

Cited by 22 publications

References 79 publications

Bacterial Nucleoid: Interplay of DNA Demixing and Supercoiling

Bacterial Nucleoid: Interplay of DNA Demixing and Supercoiling

The effects of polydisperse crowders on the compaction of the Escherichia coli nucleoid

Requirements for DNA-Bridging Proteins to Act as Topological Barriers of the Bacterial Genome

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