The shifting paradigm of chromatin structure: from the 30-nm chromatin fiber to liquid-like organization DOI Creative Commons
Kazuhiro Maeshima

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

Three-dimensional memory of nuclear organization through cell cycles DOI
Shin Fujishiro, Masaki Sasai

The Journal of Chemical Physics, Journal Year: 2025, Volume and Issue: 162(6)

Published: Feb. 13, 2025

The genome in the cell nucleus is organized by a dynamic process influenced structural memory from mitosis. In this study, we develop model of human dynamics through cycles extending previously developed whole-genome to cover mitotic phase. With extension, focus on role and cycle organization. simulation progresses mitosis interphase subsequent mitosis, leading successive cycles. During our describes microtubule dynamics, showing how forces orchestrate assembly chromosomes into rosette ring structure at metaphase. explains positioning depends their size metaphase configuration persists dimensions perpendicular division axis, effectively guiding distribution chromosome territories over multiple At onset each G1 phase, phase separation active inactive chromatin domains occurs, A/B compartmentalization. Our cycling simulations show that compartments are unaffected previous consistently established cycle. study highlights interplay between across cycles, providing insights for analyses cellular processes.

Language: Английский

Citations

1
Replication-dependent histone labeling dissects the physical properties of euchromatin/heterochromatin in living human cells DOI Creative Commons
Katsuhiko Minami, Kako Nakazato, Satoru Ide

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 28, 2025

A string of nucleosomes, where genomic DNA is wrapped around histones, organized in the cell as chromatin, ranging from euchromatin to heterochromatin, with distinct genome functions. Understanding physical differences between and heterochromatin crucial, yet specific labeling methods living cells remain limited. Here, we have developed replication-dependent histone (Repli-Histo) mark nucleosomes based on replication timing. Using this approach, investigated local nucleosome motion four known chromatin classes, human mouse cells. The more euchromatic (earlier-replicated) heterochromatic (later-replicated) regions exhibit greater lesser motions, respectively. Notably, profile each class persists throughout interphase. Genome essentially replicated although timing perturbed. Our findings, combined computational modeling, suggest that earlier-replicated accessibility, can be a major determinant genome-wide

Language: Английский

Citations

1
Chromatin structure and dynamics: one nucleosome at a time DOI
Diego M. Presman,

Belén Benítez,

Agustina L. Lafuente

et al.

Histochemistry and Cell Biology, Journal Year: 2024, Volume and Issue: 162(1-2), P. 79 - 90

Published: April 12, 2024

Language: Английский

Citations

7
Individual transcription factors modulate both the micromovement of chromatin and its long-range structure DOI Creative Commons
Haitham A. Shaban, Elias T. Friman, Cédric Deluz

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(18)

Published: April 22, 2024

The control of eukaryotic gene expression is intimately connected to highly dynamic chromatin structures. Gene regulation relies on activator and repressor transcription factors (TFs) that induce local opening closing. However, it unclear how nucleus-wide organization responds dynamically the activity specific TFs. Here, we examined two TFs with opposite effects accessibility modulate dynamics nucleus-wide. We combine high-resolution diffusion mapping dense flow reconstruction correlation in living cells obtain an imaging-based, nanometer-scale analysis processes long-range coordinated movements both show either individual transcriptional (CDX2) or (SIX6) large numbers binding sites increases mobility nucleus-wide, yet they coherent motions at micron scale. Hi-C higher-order structures shows induction pioneer factor CDX2 leads changes interactions distribution A B compartments, thus relating micromovement compartmental Given inhibition initiation elongation by RNA Pol II has a partial impact global induced CDX2, suggest overexpression alters structure dependently independently transcription. Our biophysical sequence-specific can influence multiple architectural levels, arguing brought alter its organization.

Language: Английский

Citations

7
Effect of local active fluctuations on structure and dynamics of flexible biopolymers DOI
Sayantan Dutta, Ashesh Ghosh, Andrew J. Spakowitz

et al.

Soft Matter, Journal Year: 2024, Volume and Issue: 20(8), P. 1694 - 1701

Published: Jan. 1, 2024

Active fluctuations play a significant role in the structure and dynamics of biopolymers (

Language: Английский

Citations

6
Nuclear RNA forms an interconnected network of transcription-dependent and tunable microgels DOI Creative Commons
Mattia Marenda, Davide Michieletto, Rafal Czapiewski

et al.

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

Published: June 16, 2024

Summary The human cell nucleus is comprised of proteins, chromatin and RNA, yet how they interact to form supramolecular structures drive key biological processes remains unknown. Conflicting models have proposed either a fluid-like or solid-like nature for the intranuclear microenvironment. To reconcile this discrepancy, we investigated 3D structure properties nuclear interior using experiments computer simulations. We reveal novel mechanism where newly synthesized RNA interacts with SAF-A (scaffold attachment factor A, HNRNPU), forming interconnected microgels degraded by exonuclease XRN2, leading dynamic cycles gelation fluidization. This emergent microgel network depends on transcription, disrupted depletion. It also decreases protein mobility regulates compaction modulating microphase separation, thereby opening transcriptionally active regions. tunable exhibits scale-dependent fluid- features, that suggest may regulate transcription controlling access regulatory proteins polymerases. Highlights clusters nuclear-spanning Emergent requires XRN2 activity undergo fluidization Microgel impacts Molecular dynamics modelling shows RNA/SAF-A decompaction steric hinderance Graphical Abstract

Language: Английский

Citations

6
Transcription dynamics and genome organization in the mammalian nucleus: Recent advances DOI Creative Commons
Kaustubh Wagh, Diana A. Stavreva, Gordon L. Hager

et al.

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

Published: Oct. 1, 2024

Language: Английский

Citations

6
Fluorescent protein lifetimes report densities and phases of nuclear condensates during embryonic stem-cell differentiation DOI Creative Commons
Khalil Joron, Juliane Oliveira Viegas, Liam Haas‐Neill

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 12, 2023

Fluorescent proteins (FP) are frequently used for studying inside cells. In advanced fluorescence microscopy, FPs can report on additional intracellular variables. One variable is the local density near FPs, which be useful in densities within cellular bio-condensates. Here, we show that a reduction lifetimes of common monomeric reports increased levels densities. We demonstrate use this fluorescence-based to distribution heterochromatin protein 1α (HP1α) mouse embryonic stem cells (ESCs), before and after early differentiation. find HP1α condensates pluripotent ESCs heterogeneous cannot explained by single liquid phase. Early differentiation, however, induces change towards more homogeneous densities, as liquid-like conclusion, provide method apply it distinguish between

Language: Английский

Citations

16
Deep-Learning Terahertz Single-Cell Metabolic Viability Study DOI
Ning Yang, Qian Shi, Mingji Wei

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(21), P. 21383 - 21393

Published: Sept. 28, 2023

Cell viability assessment is critical, yet existing assessments are not accurate enough. We report a cell evaluation method based on the metabolic ability of single cell. Without culture medium, we measured absorption cells to terahertz laser beams, which could target The was assessed with convolution neural classification network morphology. established model THz-AS (terahertz-absorption spectrum) results as y = (x - b)c, where x absorbance and viability, a, b, c fitting parameters model. Under water stress changes in corresponded one-to-one apoptosis process, propose 0 definition remains unchanged mechanism. Compared typical methods, our accurate, label-free, contact-free, almost interference-free help visualize process for broad applications including drug screening.

Language: Английский

Citations

13
Chromatin packing domains persist after RAD21 depletion in 3D DOI Open Access
Wing Shun Li, Lucas Carter, Luay M. Almassalha

et al.

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

Published: March 5, 2024

Abstract Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. Prior work demonstrates that RAD21 depletion results in the complete loss topologically associated loop domains on Hi-C, but corresponding change structure has not been studied using electron microscopy. Pairing scanning transmission tomography with we study role cohesin regulating spatially resolved, conformationally defined packing domains. We find only 20% are lost microscopy upon effect primarily small, poorly packed (nascent) Overall, this contrasts prevailing understanding regulation, indicating while influences domain formation, non-cohesin mediated mechanisms predominantly regulate 3D genomic

Language: Английский

Citations

5