Transcription-induced active forces suppress chromatin motion

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(12)

Опубликована: Март 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 (

Язык: Английский

---

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

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 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.

Язык: Английский

---

Phase Separation and Correlated Motions in Motorized Genome

The Journal of Physical Chemistry B, Год журнала: 2022, Номер 126(30), С. 5619 - 5628

Опубликована: Июль 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.

Язык: Английский

---

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

PRX Life, Год журнала: 2024, Номер 2(3)

Опубликована: Июль 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

Язык: Английский

---

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

Molecular Cell, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

---

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

Molecular Physics, Год журнала: 2024, Номер unknown

Опубликована: Авг. 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.

Язык: Английский

---

Mechanical Forces, Nucleus, Chromosomes, and Chromatin

Biomolecules, Год журнала: 2025, Номер 15(3), С. 354 - 354

Опубликована: Март 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.

Язык: Английский

---

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

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 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.

Язык: Английский

---

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 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.

Язык: Английский

---

BRD4 phosphorylation regulates the structure of chromatin nanodomains

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 3, 2024

ABSTRACT The interplay between chromatin structure and phase-separating proteins is an emerging topic in cell biology with implications for understanding disease states. Here, we investigate the functional relationship bromodomain protein 4 (BRD4) architecture. By combining molecular dynamics simulations live-cell imaging, demonstrate that BRD4, when mutated at specific N-terminus sites, significantly impacts nucleosome nanodomain (NN) organization dynamics. Our findings reveal enhanced binding activity of BRD4 condenses NNs, while both loss or gain reduced diffusion single nucleosomes, suggesting a role regulation nanoscale architecture microenvironment. These observations shed light on nuanced by offering insights into its maintaining nuclear transcriptional activity.

Язык: Английский

---