Chromatin fiber breaks into clutches under tension and crowding

Liu, S.; Lin, Xin; Zhang, Bin

doi:10.1101/2021.11.16.468645

Cited by 4 publications

(3 citation statements)

References 97 publications

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“…In our model, B compartments experience attractive interactions among themselves. Attractions could arise from direct contacts between histone proteins and the DNA ,, or mediated by chromatin regulators, including HP1, PRC1, and PRC2, ,,− that promote multivalent interactions. To explore the combined role of passive and active forces on genome organization, we carried out additional simulations at different interaction strengths between B compartments with varying magnitudes of active forces.…”

Section: Resultsmentioning

confidence: 99%

Phase Separation and Correlated Motions in Motorized Genome

Jiang

Kamat

et al. 2022

J. Phys. Chem. B

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The human genome is arranged in the cell nucleus nonrandomly, and phase separation has been proposed as an important driving force for genome organization. However, the cell nucleus is an active system, and the contribution of nonequilibrium activities to phase separation and genome structure and dynamics remains to be explored. We simulated the genome using an energy function parametrized with chromosome conformation capture (Hi-C) data with the presence of active, nondirectional forces that break the detailed balance. We found that active forces that may arise from transcription and chromatin remodeling can dramatically impact the spatial localization of heterochromatin. When applied to euchromatin, active forces can drive heterochromatin to the nuclear envelope and compete with passive interactions among heterochromatin that tend to pull them in opposite directions. Furthermore, active forces induce long-range spatial correlations among genomic loci beyond single chromosome territories. We further showed that the impact of active forces could be understood from the effective temperature defined as the fluctuation–dissipation ratio. Our study suggests that nonequilibrium activities can significantly impact genome structure and dynamics, producing unexpected collective phenomena.

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Section: Resultsmentioning

confidence: 99%

Phase Separation and Correlated Motions in Motorized Genome

Jiang

Kamat

et al. 2022

J. Phys. Chem. B

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“…In the future, it will be interesting to explore time-dependent features of the model, including the possibility of describing hysteresis between stretching and relaxation curves. Besides dsRNA, dsDNA, and DNA/RNA hybrid duplexes, there are other classes of molecules that also exhibit force–extension plateaus, such as myosin coiled-coils, dextrans, and chromatin fibers. − The applicability of the proposed approach to the above-mentioned systems will also be interesting to explore in the future.…”

Section: Discussionmentioning

confidence: 99%

Stretching of Long Double-Stranded DNA and RNA Described by the Same Approach

Afanasyev

Onufriev

2022

J. Chem. Theory Comput.

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We propose an approach to help interpret polymer force–extension curves that exhibit plateau regimes. When coupled to a bead–spring dynamic model, the approach accurately reproduces a variety of experimental force–extension curves of long double-stranded DNA and RNA, including torsionally constrained and unconstrained DNA and negatively supercoiled DNA. A key feature of the model is a specific nonconvex energy function of the spring. We provide an algorithm to obtain the five required parameters of the model from experimental force–extension curves. The applicability of the approach to the force–extension curves of double-stranded (ds) DNA of variable GC content as well as to a DNA/RNA hybrid structure is explored and confirmed. We use the approach to explain counterintuitive sequence-dependent trends and make predictions. In the plateau region of the force–extension curves, our molecular dynamics simulations show that the polymer separates into a mix of weakly and strongly stretched states without forming macroscopically distinct phases. The distribution of these states is predicted to depend on the sequence.

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“…In our model, B compartments experience attractive interactions among themselves. Attractions could arise from direct contacts between histone proteins and the DNA 44,77,78 or mediated by chromatin regulators, including HP1, PRC1, and PRC2, 40,41,[79][80][81] that promote multivalent interactions. To explore the combined role of passive and active forces on genome organization, we carried out additional simulations at different interaction strengths between B compartments with varying magnitudes of active forces.…”

Section: Balancing Passive and Active Forces For Heterochromatin Loca...mentioning

confidence: 99%

Phase Separation and Correlated Motions in Motorized Genome

Jiang

Kamat

et al. 2022

Preprint

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The human genome is arranged in the cell nucleus non-randomly, and phase separation has been proposed as an important driving force for genome organization. However, the cell nucleus is an active system, and the contribution of non-equilibrium activities to phase separation and genome structure and dynamics remains to be explored. We simulated the genome using an energy function parameterized with chromosome conformation capture (Hi-C) data with the presence of active, nondirectional forces that break the detailed balance. We found that active forces that may arise from transcription and chromatin remodeling can dramatically impact the spatial localization of heterochromatin. When applied to euchromatin, active forces can drive heterochromatin to the nuclear envelope and compete with passive interactions among heterochromatin that tend to pull them in opposite directions. Furthermore, active forces induce long-range spatial correlations among genomic loci beyond single chromosome territories. We further showed that the impact of active forces could be understood from the effective temperature defined as the fluctuation-dissipation ratio. Our study suggests that non-equilibrium activities can significantly impact genome structure and dynamics, producing unexpected collective phenomena.

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Chromatin fiber breaks into clutches under tension and crowding

Cited by 4 publications

References 97 publications

Phase Separation and Correlated Motions in Motorized Genome

Phase Separation and Correlated Motions in Motorized Genome

Stretching of Long Double-Stranded DNA and RNA Described by the Same Approach

Phase Separation and Correlated Motions in Motorized Genome

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