The Material Properties of the Cell Nucleus: A Matter of Scale

Cells, Journal Year: 2023, Volume and Issue: 12(15), P. 1958 - 1958

Published: July 28, 2023

Chromatin regulatory processes physically take place in the environment of cell nucleus, which is filled with chromosomes and a plethora smaller biomolecules. The nucleus contains macromolecular assemblies different sizes, from nanometer-sized protein complexes to micrometer-sized biomolecular condensates, chromosome territories, nuclear bodies. This multiscale organization impacts transport within interior, global mechanical properties way senses reacts stimuli. Here, we discuss recent work on these aspects, including microrheology micromanipulation experiments assessing material its subcomponents. We summarize how media depend time length scales probed experiment, reconcile seemingly contradictory observations made scales. also revisit concept liquid-like solid-like for complex such as nucleus. propose that can be considered viscoelastic medium composed three major components distinct properties: lamina, chromatin network, nucleoplasmic fluid. multicomponent enables serve functions reaction nanoscale mechanosensor structural scaffold microscale.

Language: Английский

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Multiscale Bayesian simulations reveal functional chromatin condensation of gene loci

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(6)

Published: May 31, 2024

Abstract Chromatin, the complex assembly of DNA and associated proteins, plays a pivotal role in orchestrating various genomic functions. To aid our understanding principles underlying chromatin organization, we introduce Hi-C metainference, Bayesian approach that integrates contact frequencies into multiscale prior models chromatin. This combines both bottom-up (the physics-based prior) top-down data-driven posterior) strategies to characterize 3D organization target locus. We first demonstrate capability this method accurately reconstruct structural ensemble dynamics system from information. then apply investigate Sox2, Pou5f1, Nanog loci mouse embryonic stem cells using model at 1 kb resolution. observe studied are conformationally heterogeneous organized as crumpled globules, favoring contacts between distant enhancers promoters. Using nucleosome-resolution simulations, reveal how gene is functionally across multiple scales At local level, identify diverse tetranucleosome folding motifs with characteristic distribution along genome, predominantly open cis-regulatory elements compact between. larger scale, find enhancer–promoter driven by transient condensation domains stabilized extensive internucleosome interactions. Overall, work highlights condensed, but dynamic nature vivo, contributing deeper structure–function relationships.

Language: Английский

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CG modeling of nucleosome arrays reveals the salt-dependent chromatin fiber conformational variability

The Journal of Chemical Physics, Journal Year: 2025, Volume and Issue: 162(2)

Published: Jan. 8, 2025

Eukaryotic DNA is packaged in the cell nucleus into chromatin, composed of arrays DNA–histone protein octamer complexes, nucleosomes. Over past decade, it has become clear that chromatin structure vivo not a hierarchy well-organized folded nucleosome fibers but displays considerable conformational variability and heterogeneity. In vitro studies, as well computational modeling, have revealed attractive nucleosome–nucleosome interaction with an essential role stacking defines compaction. The internal compacted regulated by flexible dynamic histone N-terminal tails. Since highly negatively charged polyelectrolyte, electrostatic forces make decisive contribution to formation require histones, particularly tails, carry significant positive charge. This also results mobile cations cytoplasm (K+, Na+, Mg2+) regulating interactions. Building on previously successfully established bottom-up coarse-grained (CG) model, we developed CG array (chromatin fiber) model explicit presence ions studied its function Na+ Mg2+ ion concentration. With progressively elevated concentrations, identified four main states characterized extended, flexible, nucleosome-clutched, globular fibers.

Language: Английский

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Chromatin domains in the cell: Phase separation and condensation

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 91, P. 103006 - 103006

Published: Feb. 20, 2025

Language: Английский

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The shifting paradigm of chromatin structure: from the 30-nm chromatin fiber to liquid-like organization

Proceedings of the Japan Academy Series B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The organization and dynamics of chromatin are critical for genome functions such as transcription DNA replication/repair. Historically, was assumed to fold into the 30-nm fiber progressively arrange larger helical structures, described in textbook model. However, over past 15 years, extensive evidence including our studies has dramatically transformed view from a static, regular structure one that is more variable dynamic. In higher eukaryotic cells, forms condensed yet liquid-like domains, which appear be basic unit structure, replacing fiber. These domains maintain proper accessibility, ensuring regulation reaction processes. During mitosis, these assemble form gel-like mitotic chromosomes, further constrained by condensins other factors. Based on available evidence, I discuss physical properties live emphasizing its viscoelastic nature-balancing local fluidity with global stability support functions.

Language: Английский

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