The solid and liquid states of chromatin

Hansen, Jeffrey C.; Maeshima, Kazuhiro; Hendzel, Michael J.

doi:10.1186/s13072-021-00424-5

Cited by 74 publications

(55 citation statements)

References 220 publications

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“…Recent evidence has suggested a dual nature of chromatin 62, 63 . Transitions between liquid and solid states of chromatin ensembles are still not well understood 62 . Whereas constrained local motions of nucleosomes occur on the seconds timescale, solid chromatin at mesoscale does not mix with its environment on the minutes to hours timescale.…”

Section: Discussionmentioning

confidence: 99%

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True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Gelléri

Chen

Szczurek

et al. 2022

Preprint

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Chromatin compaction differences may have a strong impact on accessibility of individual macromolecules and macromolecular assemblies to their DNA target sites. Estimates based on fluorescence microscopy with conventional resolution, however, suggested only modest compaction differences (~2-10x) between active and inactive nuclear compartments (ANC and INC). Here, we present maps of nuclear landscapes with true-to-scale DNA-densities, ranging from <5 Mbp/μm3 to >300 Mbp/μm3. Maps were generated from individual human and mouse cell nuclei with single-molecule localization microscopy at ~20 nm lateral and ~100 nm axial resolution and supplemented by electron spectroscopic imaging. Live cell microinjection experiments with 20 nm and 40 nm sized fluorescent beads, corresponding to macromolecular assemblies for transcription and replication, indicated movements within the ANC, but exclusion from the INC. In line with previous studies of transcription, pulse-chase labeling experiments of DNA demonstrated replication within the ANC, followed by re-location of replicated, inactive chromatin into the INC.

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Section: Discussionmentioning

confidence: 99%

“…Recent evidence has suggested a dual nature of chromatin 62, 63 . Transitions between liquid and solid states of chromatin ensembles are still not well understood 62 .…”

Section: Discussionmentioning

confidence: 99%

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Gelléri

Chen

Szczurek

et al. 2022

Preprint

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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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“…However, there are also many compelling reasons for treating chromatin (as opposed to DNA) as a self-attractive polymer in poor solvents. The chromatin histone tails that are positively charged attract the negatively charged DNA linkers (in regions that can be far along the contour length of the chain, but close in three-dimensional space), leading to chromatin self-attraction and water acting as a poor solvent [29][30][31][32][33][34]. In addition, the HP1 chromatin-binding proteins are phase separated within the nucleus and may contribute to (hetero)chromatin condensation [35,36].…”

Section: Introductionmentioning

confidence: 99%

Polymer dynamics relates chromosome mixing to temporal changes in biological contact maps

Bajpai

Safran

2022

Preprint

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Chromosomes are arranged in distinct territories within the nucleus of animal cells. Recent experiments have shown that these territories overlap at their edges, suggesting partial mixing during interphase. Genomewide, biological contact maps in humans and Drosophila show only a low degree of contact between different chromosomes; however, the mixing in yeast is considerably higher. Recent theoretical estimates considered topological mixing of chromosomes by polymer reptation, and suggested that the time scale for chromosome mixing is years. This implies that a cell will typically divide before its chromosomes mix by reptation. Here, we use a generic polymer simulation to quantify the dynamics of chromosome mixing over time. We introduce the chromosome mixing index that quantifies the mixing of distinct chromosomes in the nucleus. We find that the chromosome mixing index increases as a power-law with time, and the scaling exponent varies non-monotonically with self-interaction and volume fraction. By comparing the chromosome mixing index with both subdiffusion due to (nontopological) intermingling of chromosomes as well as longer-time reptation, we show that the scaling exponent of the chromosome mixing index is related to intermingling for relatively small chromosome attractions and to reptation for large attractions. The model is extended to realistic biological conditions.

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The solid and liquid states of chromatin

Cited by 74 publications

References 220 publications

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Phase Separation and Correlated Motions in Motorized Genome

Polymer dynamics relates chromosome mixing to temporal changes in biological contact maps

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