Biophysical aspect of assembly and regulation of nuclear bodies scaffolded by architectural RNA

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: 437(9), P. 169016 - 169016

Published: Feb. 18, 2025

Language: Английский

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Regulation of chromatin microphase separation by binding of protein complexes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 12, 2023

We show evidence of the association RNA polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent microphase separation where cores comprise dense and shell, RNAP low density. These observations motivate our physical model for regulation organization. Here, we as multiblock copolymer, comprising active inactive regions (blocks) that are both poor solvent tend to be condensed absence binding proteins. However, quality can regulated by protein complexes (e.g., transcription factors). Using theory polymer brushes, find such leads swelling which turn modifies spatial organization regions. In addition, use simulations study spherical micelles, whose shells bound complexes. micelles increases number controls their size. Thus, genetic modifications affecting strength chromatin-binding may modulate experienced regulate genome.

Language: Английский

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HP1-driven phase separation recapitulates the thermodynamics and kinetics of heterochromatin condensate formation

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(33)

Published: Aug. 7, 2023

The spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid–liquid phase separation properties in vitro, its mechanistic impact on structure and dynamics PCH condensate formation vivo remains largely unresolved. Here, using a minimal theoretical framework, we systematically investigate mutual coupling between self-interacting HP1-like molecules chromatin polymer. We reveal that specific affinity for H3K9me2/3 loci facilitates coacervation nucleo promotes stable condensates at levels far below concentration required observe purified protein assays vitro. These heterotypic HP1–chromatin interactions give rise strong dependence nucleoplasmic density HP1-H3K9me2/3 stoichiometry, consistent with thermodynamics multicomponent separation. dynamical cross talk viscoelastic scaffold also leads anomalously slow equilibration kinetics, which strongly depend distribution domains result coexistence multiple long-lived, microphase-separated compartments. morphology these complex coacervates is further found be governed by dynamic establishment underlying landscape, may drive their increasingly abnormal, aspherical shapes during cell development. findings compare favorably 4D microscopy measurements live Drosophila embryos suggest general quantitative model based interplay HP1-based polymer mechanics.

Language: Английский

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Molecular dynamics simulations of nucleosomes are coming of age

Wiley Interdisciplinary Reviews Computational Molecular Science, Journal Year: 2024, Volume and Issue: 14(4)

Published: July 1, 2024

Abstract Understanding the function of eukaryotic genomes, including human genome, is undoubtedly one major scientific challenges 21st century. The cornerstone genome organization nucleosomes—elementary building blocks chromatin about 10 nm in size that wrap DNA around an octamer histone proteins. Nucleosomes are integral players all genomic processes, transcription, replication and repair. They mediate regulation at epigenetic level, bridging discrete nature genetic information encoded with analog physical intermolecular interactions required to access information. Due their relatively large dynamic nature, nucleosomes difficult objects for experimental characterization. Molecular dynamics (MD) simulations have emerged over years as a useful tool complement studies. Particularly recent years, advances computing power, refinement MD force fields codes opened up new frontiers terms simulation timescales quality related systems. It has become possible elucidate atomistic detail functional modes such unwrapping sliding, characterize effects modifications, protein sequence variation on nucleosome structure stability, describe mechanisms governing chromatin‐associated proteins formation supranucleosome structures. In this review, we systematically analyzed all‐atom studies structures published since 2018 discussed relevance context older studies, data, coarse‐grained multiscale This article categorized under: Software > Modeling Statistical Mechanics Dynamics Monte‐Carlo Methods Structure Mechanism Computational Biochemistry Biophysics

Language: Английский

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Active Loop Extrusion Guides DNA-Protein Condensation

Physical Review Letters, Journal Year: 2025, Volume and Issue: 134(12)

Published: March 26, 2025

The spatial organization of DNA involves loop extrusion and the formation protein-DNA condensates. While significance each process is increasingly recognized, their interplay remains unexplored. Using molecular dynamics simulation theory we investigate this interplay. Our findings reveal that can enhance condensation promotes coalescence ripening Further, enables condensate under tension position concurrent presence results in distinct domains similar to TADs, an outcome not achieved by either alone. Published American Physical Society 2025

Language: Английский

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Transport of partially active polymers in chemical gradients

Soft Matter, Journal Year: 2025, Volume and Issue: 21(10), P. 1835 - 1840

Published: Jan. 1, 2025

The transport of molecules for chemical reactions is critically important in various cellular biological processes. Despite thermal diffusion being prevalent many biochemical processes, it unreliable any sort directed or preferential accumulation molecules. In this paper, we propose a strategy motion which the are transported by partially active polymeric structures. These polymers assumed to be Rouse chains, monomers connected via harmonic springs and these chains studied environments that have activity varying spatially. such facilitated chemical/activity gradients generate an effective drift. By marginalizing out degrees freedom system, obtain Fokker-Planck equation modes polymer. particular, solve steady state distribution center mass its mean first passage time reach intended destination. We focus on how arrangement units within polymer affects steady-state dynamic behavior they can optimized achieve high rapid motility.

Language: Английский

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Cononsolvency Effect: When the Hydrogen Bonding between a Polymer and a Cosolvent Matters

Macromolecules, Journal Year: 2022, Volume and Issue: 55(24), P. 11034 - 11050

Published: Dec. 5, 2022

Despite the fact that observation of cononsolvency was reported as early four decades ago, its phase-transition mechanism is still under debate. In this work, we provided a comprehensive study phase behaviors poly(N-isopropylacrylamide) (PNiPAAm) in sulfoxide or sulfone aqueous solutions. We observed sharp collapse transition PNiPAAm brushes but not solutions by equilibrium measurements situ spectroscopic ellipsometry. found hydrogen-bond formation between oxygens and amide hydrogens polymer chains plays critical role regulating PNiPAAm. have extended concept preferential adsorption taking into account hydrophobic interactions cosolvent molecules, which are adsorbed on hydrogen bonds. This can explain experimental observations these solvent mixtures sheds light understanding where bonds interaction play role. Our results also be interest for liquid–liquid separation living cell condensation proteins bound to large biomacromolecules an essential

Language: Английский

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Polymer Collapse & Liquid-Liquid Phase-Separation are Coupled in a Generalized Prewetting Transition

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

Published: April 30, 2024

The three-dimensional organization of chromatin is thought to play an important role in controlling gene expression. Specificity expression achieved through the interaction transcription factors and other nuclear proteins with particular sequences DNA. At unphysiological concentrations many these can phase-separate absence DNA, it has been hypothesized that, vivo, thermodynamic forces driving phases help determine chromosomal organization. However unclear how itself a long polymer subject configurational transitions, interacts protein phases. Here we show that compressible be coupled interacting mixtures, leading generalized prewetting transition where collapse coincident locally stabilized liquid droplet. We use lattice Monte-Carlo simulations mean-field theory stable even regimes both coexisting are unstable isolation, new transitions either abrupt or continuous. For polymers internal linear structure further changes concentration bulk components lead structure. In nucleus there distinct interact different regions chromatin, potentially giving rise Prewet simple systems consider here highlight chromatin’s as lower-dimensional surface whose interactions required for novel

Language: Английский

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Role of protein–protein interactions on organization and dynamics of a model chromatin

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 161(13)

Published: Oct. 1, 2024

The three-dimensional organization of chromatin is influenced by chromatin-binding proteins through both specific and non-specific interactions. However, the roles sequence interactions between binding in shaping structure remain elusive. By employing a simple polymer-based model that explicitly considers sequence-dependent protein protein–protein interactions, we elucidate mechanism for organization. We find tuning concentration sufficient to either promote or inhibit compartmentalization. Moreover, attraction strongly affect structural dynamic exponents describe spatiotemporal chromatin. Strikingly, our model’s predictions governing dynamics successfully capture experimental observations, sharp contrast previous models. Overall, findings have potential reinterpret data obtained from various chromosome conformation technologies, laying groundwork advancing understanding

Language: Английский

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Spatial and Temporal Organization of Chromatin at Small and Large Scales

Annual Review of Condensed Matter Physics, Journal Year: 2022, Volume and Issue: 14(1), P. 193 - 210

Published: Nov. 9, 2022

DNA molecules with a total length of two meters contain the genetic information in every cell our body. To control access to genes, organize its spatial structure nucleus, and duplicate faithfully separate material, makes use sophisticated physical mechanisms. Base pair sequences multiplex various layers information, chromatin remodelers mobilize nucleosomes via twist defects, loop extruders create system nonconcatenated rings spatially chromatin, biomolecular condensates concentrate proteins nucleic acids specialized membraneless compartments. In this review, we discuss current state understanding some these mechanisms that influence organization material space time.

Language: Английский

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