Transcription-induced active forces suppress chromatin motion

Shin, Sungwon; Cho, Hyun Woo; Shi, Guang; Thirumalai, D.

doi:10.1101/2022.04.30.490180

Cited by 8 publications

(9 citation statements)

References 122 publications

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“…The cell nucleus is an active system enriched with ATP-driven processes. The ideal potential was specifically designed to account for the role of molecular motors like cohesin that can compact individual chromosomes. , Other active processes, including transcription and nucleosome remodeling, ,,− can also lead to nonconservative forces to perturb chromosome structures. The effect of these processes, together with passive interactions arising from epigenetic modifications and chromatin regulators, may produce the effective compartment specific potential inferred from Hi-C data.…”

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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“…However, there is mounting experimental evidence in favor of this. RNA Pol II-mediated transcription has been shown to constrain nucleosome mobility ( 7, 12 ). Consistent with this result, TF binding and subsequent recruitment of the transcriptional machinery could trigger a transition of the local chromatin polymer (and of the bound TF) from state 2 to state 1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…This is a highly dynamic process with TFs only transiently interacting with chromatin on a timescale of seconds (4)(5)(6). Chromatin itself is a highly dynamic polymer, subject to thermal fluctuations and active forces such as transcription (7), loop extrusion (8), DNA damage repair, and replication (9). How TFs navigate this complex nuclear microenvironment to find their binding sites remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Single-molecule tracking reveals two low-mobility states for chromatin and transcriptional regulators within the nucleus

Wagh

Stavreva

Jensen

et al. 2022

Preprint

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How transcription factors (TFs) navigate the complex nuclear environment to assemble the transcriptional machinery at specific genomic loci remains elusive. Using single-molecule tracking, coupled with machine learning, we examined the mobility of multiple transcriptional regulators. We show that H2B and ten different transcriptional regulators display two distinct low-mobility states. Our results indicate that both states represent dynamic interactions with chromatin. Ligand activation results in a dramatic increase in the proportion of steroid receptors in the lowest mobility state. Mutational analysis revealed that only chromatin interactions in the lowest mobility state require an intact DNA-binding domain as well as oligomerization domains. Importantly, these states are not spatially separated as previously believed but in fact, individual H2B and TF molecules can dynamically switch between them. Together, our results identify two unique and distinct low-mobility states of transcriptional regulators that appear to represent common pathways for transcription activation in mammalian cells.

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“…The ideal potential was specifically designed to account for the role of molecular motors like Cohesin that can compact individual chromosomes. 55,56 Other active processes, including transcription and nucleosome remodeling, 51,53,[68][69][70][71] can also lead to non-conservative forces to perturb chromosome structures. The effect of these processes, together with passive interactions arising from epigenetic modifications and chromatin regulators, may produce the effective compartment specific potential inferred from Hi-C data.…”

Section: Active Forces Drive Peripheral Localization Of Heterochromatinmentioning

confidence: 99%

Phase Separation and Correlated Motions in Motorized Genome

Jiang

Kamat

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Transcription-induced active forces suppress chromatin motion

Cited by 8 publications

References 122 publications

Phase Separation and Correlated Motions in Motorized Genome

Phase Separation and Correlated Motions in Motorized Genome

Single-molecule tracking reveals two low-mobility states for chromatin and transcriptional regulators within the nucleus

Phase Separation and Correlated Motions in Motorized Genome

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