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Phase Separation and Correlated Motions in Motorized Genome

Zhongling Jiang, Yifeng Qi, View ORCID ProfileKartik Kamat, View ORCID ProfileBin Zhang
doi: https://doi.org/10.1101/2022.05.10.491350
Zhongling Jiang
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
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Yifeng Qi
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
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Kartik Kamat
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
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Bin Zhang
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • For correspondence: binz@mit.edu
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 10, 2022.
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Phase Separation and Correlated Motions in Motorized Genome
Zhongling Jiang, Yifeng Qi, Kartik Kamat, Bin Zhang
bioRxiv 2022.05.10.491350; doi: https://doi.org/10.1101/2022.05.10.491350
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Phase Separation and Correlated Motions in Motorized Genome
Zhongling Jiang, Yifeng Qi, Kartik Kamat, Bin Zhang
bioRxiv 2022.05.10.491350; doi: https://doi.org/10.1101/2022.05.10.491350

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