DNA Replication and Polymer Chain Duplication Reshape the Genome in Space and Time DOI Creative Commons
Dario D’Asaro, Maxime M. C. Tortora, Cédric Vaillant

et al.

Physical Review X, Journal Year: 2024, Volume and Issue: 14(4)

Published: Oct. 22, 2024

In eukaryotes, DNA replication constitutes a complex process whereby multiple origins are stochastically fired, and from which the machinery proceeds along chromosomes to achieve faithful synthesis of two identical copies genome during S phase cell cycle. Experimental evidence shows functional correlation between dynamics spatial organization inside nuclei, suggesting that replicating may impact chromosome folding. However, theoretical mechanistic bases such hypothesis remain elusive. To address question, we propose quantitative, minimal framework integrates polymer chain by accounting explicitly for progression resulting formation sister chromatids. By systematically characterizing 3D structural consequences replication, possible interactions active machineries, show transient loops potentially across temporal scales, level individual global chain. Comparison with available microscopy conformation capture data in yeast suggests replication-dependent loop extrusion be acting , shape as loose bottle brushes phase. Lastly, explore postreplication relative chromatids demonstrate emergence catenations intertwined structures, regulated density fired origins. Published American Physical Society 2024

Language: Английский

The chromosome folding problem and how cells solve it DOI Creative Commons
Job Dekker, Leonid A. Mirny

Cell, Journal Year: 2024, Volume and Issue: 187(23), P. 6424 - 6450

Published: Nov. 1, 2024

Every cell must solve the problem of how to fold its genome. We describe folded state chromosomes is result combined activity multiple conserved mechanisms. Homotypic affinity-driven interactions lead spatial partitioning active and inactive loci. Molecular motors through loop extrusion. Topological features such as supercoiling entanglements contribute chromosome folding dynamics, tethering loci sub-nuclear structures adds additional constraints. Dramatically diverse conformations observed throughout cycle across tree life can be explained differential regulation implementation these basic propose that first functions are mediate genome replication, compaction, segregation mechanisms have subsequently been co-opted for other roles, including long-range gene regulation, in different conditions, types, species.

Language: Английский

Citations

10
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
DNA topology: A central dynamic coordinator in chromatin regulation DOI

Shuai Li,

Charan Vemuri,

Chongyi Chen

et al.

Current Opinion in Structural Biology, Journal Year: 2024, Volume and Issue: 87, P. 102868 - 102868

Published: June 14, 2024

Language: Английский

Citations

6
Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis DOI Creative Commons
Andreas Brunner, Natalia Rosalía Morero, Wanlu Zhang

et al.

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

Published: May 30, 2024

How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that transition from a Condensin to Cohesin-based occurs dynamically over two hours. While significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes sufficient build first TAD structures. By contrast, more abundant Cohesin-STAG2 accumulates on only gradually later responsible for compaction inside structures forms paired upon completed nuclear import. Our time-resolved mapping mitotic loop extruders single reveals nested architecture formed by sequential action seamlessly replaced less compact, but conceptually similar hierarchically driven Cohesins.

Language: Английский

Citations

5
Behind the stoNE wall: a fervent activity for nuclear lipids DOI Creative Commons

Kseniya Samardak,

Janélie Bâcle,

María Moriel‐Carretero

et al.

Biochimie, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

5
CiFi: Accurate long-read chromatin conformation capture with low-input requirements DOI Creative Commons
Sean P. McGinty, Gulhan Kaya, Sheina B. Sim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

ABSTRACT By coupling chromatin conformation capture (3 C ) with PacBio H iFi long-read sequencing, we have developed a new method (CiFi) that enables analysis of genome interactions across repetitive genomic regions low-input requirements. CiFi produces multiple interacting concatemer segments per read, facilitating assembly and scaffolding. Together, the approach previously recalcitrant low-complexity loci, small organisms such as single insect individuals.

Language: Английский

Citations

0
Improved cohesin HiChIP protocol and bioinformatic analysis for robust detection of chromatin loops and stripes DOI Creative Commons
Karolina Jodkowska, Zofia Parteka, Abhishek Agarwal

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 14, 2025

Abstract Chromosome Conformation Capture (3 C) methods, including Hi-C (a high-throughput variation of 3 C), detect pairwise interactions between DNA regions, enabling the reconstruction chromatin architecture in nucleus. HiChIP is a modification experiment that includes immunoprecipitation (ChIP) step, allowing genome-wide identification contacts mediated by protein interest. In mammalian cells, cohesin complex one major players establishment loops. We present an improved experimental protocol. Using comprehensive bioinformatic analysis, we show dual fixation method compared to standard formaldehyde-only method, results substantially better signal-to-noise ratio, increased ChIP efficiency and detection loops architectural stripes. Additionally, propose automated pipeline called nf-HiChIP ( https://github.com/SFGLab/hichip-nf-pipeline ) for processing samples starting from raw sequencing reads data ending with set significant (loops), which allows efficient timely analysis multiple parallel, without requiring additional ChIP-seq experiments. Finally, using advanced approaches biophysical modelling stripe calling generate accurate loop extrusion polymer models region interest provide detailed picture stripes, respectively.

Language: Английский

Citations

0
Functional interplay between condensin I and topoisomerase IIα in single-molecule DNA compaction DOI Open Access
Yuko Tsubota, Keishi Shintomi, Kazuhisa Kinoshita

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Condensin I and topoisomerase IIα (topo IIα) are chromosomal ATPases essential for mitotic chromosome assembly. Mechanistically how the two cooperate to assemble chromosomes remains unknown. Here we use total internal reflection fluorescence microscopy analyze interplay between condensin topo at single-molecule resolution. As observed in previous studies, alone predominantly forms DNA loops an ATP-dependent manner. However, when is included reaction, stable compact structures (termed “lumps”) a manner dependent on C-terminal domain of IIα. Each lumps contains single complex dimer. Remarkably, find that IIα, catalytically active, renders resistant protease treatment. Several lines evidence show protease-resistant contain knotted DNA. A mutant defective ATP hydrolysis, together with smaller which probability knotting greatly reduced. Our results demonstrate IIα-mediated strand passage coupled I-mediated loop extrusion generate structure. Together recent discuss functional implications these observations assembly stabilization.

Language: Английский

Citations

0
TOP2B is required for compartment strength changes upon retinoic acid treatment in SH-SY5Y cells DOI Creative Commons
Erica M. Hildebrand, Johnny Lo, Mushtaq M. Khazeem

et al.

Chromosome Research, Journal Year: 2025, Volume and Issue: 33(1)

Published: April 4, 2025

Language: Английский

Citations

0
Polymer model integrates imaging and sequencing to reveal how nanoscale heterochromatin domains influence gene expression DOI Creative Commons

Vinayak Vinayak,

Ramin Basir, Rosela Golloshi

et al.

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

Citations

0