Transcription-induced active forces suppress chromatin motion

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(12)

Published: March 15, 2024

The organization of interphase chromosomes in a number species is starting to emerge thanks advances variety experimental techniques. However, much less known about the dynamics, especially functional states chromatin. Some experiments have shown that motility individual loci human chromosome decreases during transcription and increases upon inhibiting transcription. This counterintuitive finding because it thought active mechanical force (

Language: Английский

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Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 25, 2024

Abstract Although our understanding of the involvement heterochromatin architectural factors in shaping nuclear organization is improving, there still ongoing debate regarding role active genes this process. In study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate relationship between gene transcription and 3D folding. Our analysis uncovers a nonmonotonic - globally positive correlation intragenic contact density Pol II occupancy, independent cohesin-based loop extrusion. Through development biophysical model integrating dynamics within polymer chromosome organization, demonstrate that II-mediated attractive interactions with limited valency transcribed regions yield quantitative predictions consistent chromosome-conformation-capture live-imaging experiments. work provides compelling evidence transcriptional activity shapes 4D genome through micro-compartmentalization.

Language: Английский

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Temporally Correlated Active Forces Drive Segregation and Enhanced Dynamics in Chromosome Polymers

PRX Life, Journal Year: 2024, Volume and Issue: 2(3)

Published: July 23, 2024

Understanding the mechanisms governing structure and dynamics of flexible polymers like chromosomes, especially signatures motor-driven active processes, is great interest in genome biology. We study chromosomes as a coarse-grained polymer model where microscopic motor activity captured via an additive temporally persistent noise. The steady state characterized by two parameters: force, controlling persistent-noise amplitude, correlation time, decay time find that drives correlated motion over long distances regime dynamic compaction into globally collapsed entangled globule. Diminished topological constraints destabilize globule, segments trapped globule move toward periphery, resulting enriched monomer density near periphery. also show heterogeneous leads to segregation highly species from less one, suggesting role chromosome compartmental segregation. Adding experimental-data-derived structures, we loci may mechanically perturb switch compartments established epigenetics-driven passive self-association. key distinguishing are enhanced apparent diffusivity, exploration all regimes (subdiffusion, effective diffusion, superdiffusion) at various lag times, broadened distribution observables exponents. Published American Physical Society 2024

Language: Английский

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Phase Separation and Correlated Motions in Motorized Genome

The Journal of Physical Chemistry B, Journal Year: 2022, Volume and Issue: 126(30), P. 5619 - 5628

Published: July 20, 2022

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

Language: Английский

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Transcription dynamics and genome organization in the mammalian nucleus: Recent advances

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Coil-to-globule collapse of active polymers: a Rouse perspective

Molecular Physics, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

We derive an effective Rouse model for tangentially active polymers, characterised by a constant force tangent to their backbone. In particular, we show that, once extended account finite bending rigidity, such captures the reduction in gyration radius, or coil-to-globule-like transition, that has been observed numerically literature filaments. Interestingly, our analysis identifies proper definition of Peclet number, allows collapse all numerical data onto master curve.

Language: Английский

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Mechanical Forces, Nucleus, Chromosomes, and Chromatin

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 354 - 354

Published: March 1, 2025

Individual cells and within the tissues organs constantly face mechanical challenges, such as tension, compression, strain, shear stress, rigidity of cellular extracellular surroundings. Besides external forces, their components are also subjected to intracellular pulling, pushing, stretching, created by sophisticated force-generation machinery cytoskeleton molecular motors. All these stressors switch on mechanotransduction pathways, allowing respond adapt. Mechanical force-induced changes at cell membrane transmitted nucleus its nucleoskeleton, affecting nucleocytoplasmic transport, chromatin conformation, transcriptional activity, replication, genome, which, in turn, orchestrate behavior. The memory mechanoresponses is stored epigenetic structure modifications. state response acellular environment determines identity, fate, immune invading pathogens. Here, we give a short overview latest developments understanding processes, emphasizing effects nuclei, chromosomes, chromatin.

Language: Английский

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Polymer model integrates imaging and sequencing to reveal how nanoscale heterochromatin domains influence gene expression

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 23, 2025

Abstract Chromatin organization regulates gene expression, with nanoscale heterochromatin domains playing a fundamental role. Their size varies microenvironmental stiffness and epigenetic interventions, but how these factors regulate their formation influence transcription remains unclear. To address this, we developed sequencing-informed copolymer model that simulates chromatin evolution through diffusion active reactions. Our predicts the of quantifies domain scales reaction rates, showing compaction changes primarily occur at boundaries. We validated predictions via Hi-C super-resolution imaging hyperacetylated melanoma cells identified differential expression metastasis-related genes RNA-seq. our findings in hMSCs, where rates respond to stiffness. Conclusively, simulations reveal boundaries memory. These demonstrate external cues drive transcriptional memory development disease.

Language: Английский

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Temporally correlated active forces drive segregation and enhanced dynamics in chromosome polymers

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 24, 2023

Understanding the mechanisms governing structure and dynamics of flexible polymers like chromosomes, especially, signatures motor-driven active processes is great interest in genome biology. We study chromosomes as a coarse-grained polymer model where microscopic motor activity captured via an additive temporally persistent noise. The steady state characterized by two parameters: force, controlling persistent-noise amplitude, correlation time, decay time find that drives correlated motion over long distances regime dynamic compaction into globally collapsed entangled globule. Diminished topological constraints destabilize globule, segments trapped globule move toward periphery, resulting enriched monomer density near periphery. also show heterogeneous leads to segregation highly species from less one, suggesting role chromosome compartmental segregation. Adding experimental-data-derived structures, we loci may mechanically perturb switch compartments established epigenetics-driven passive self-association. key distinguishing are enhanced apparent diffusivity, exploration all regimes (sub-diffusion, effective diffusion, super-diffusion) at various lag times, broadened distribution observables exponents.

Language: Английский

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Polymer Model Integrates Super-Resolution Imaging and Epigenomic Sequencing to Elucidate the Role of Epigenetic Reactions in Shaping 4D Chromatin Organization

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 12, 2024

Abstract Chromatin, with its complex spatial and temporal organization, plays a crucial role in regulating gene expression. Recent advancements super-resolution microscopy have revealed that nanoscale domains of heterochromatin (repressed segments) embedded within euchromatin (active background are fundamental units 3D chromatin organization. In tissue-resident cells, the size these varies microenvironment, particularly stiffness, organization is also influenced by pharmacological epigenetic drugs. However, mechanisms governing domain under various conditions their impact on expression remain unclear. To address this knowledge gap, we developed dynamic, next-generation sequencing informed copolymer model. Our model simulates spatiotemporal evolution chromatin, driven passive diffusion active reactions, which interconvert heterochromatin. By integrating chromatin-chromatin interaction energetics diffusion-reaction dynamics, predict formation heterochromatin-rich establish scaling relationship between modulation reaction rates. Additionally, our predicts compaction changes response to global rates occur predominantly at boundaries. We validated predictions via Hi-C contact map analysis imaging hyperacetylated melanoma cells. Subsequent RNA-seq suggested pivotal shifts influencing metastatic potential further mesoscale findings against rearrangement hMSCs, exhibit sensitivity microenvironmental stiffness. Finally, evaluated effects cycling silico, mimicking cellular transition different extracellular conditions, back again. This finding reveals cell-type invariant mechanism boundaries, whereby guides memory formation. show reorganization resulting from alterations drug exposure disease progression impacts both immediate responses long-term memory.

Language: Английский

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