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

Liquid–Liquid Phase Separation in Chromatin DOI Open Access
Karsten Rippe

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(2), P. a040683 - a040683

Published: June 14, 2021

Karsten Rippe Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, 69120 Heidelberg, Germany Correspondence: Karsten.Rippe{at}dkfz.de

Language: Английский

Citations

110
HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics DOI Creative Commons
Amy R. Strom, Ronald Biggs, Edward J. Banigan

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: June 9, 2021

Chromatin, which consists of DNA and associated proteins, contains genetic information is a mechanical component the nucleus. Heterochromatic histone methylation controls nucleus chromosome stiffness, but contribution heterochromatin protein HP1α (CBX5) unknown. We used novel auxin-inducible degron human cell line to rapidly degrade HP1α. Degradation did not alter transcription, local chromatin compaction, or methylation, decrease stiffness. Single-nucleus micromanipulation reveals that essential chromatin-based mechanics maintains nuclear morphology, separate from methylation. Further experiments with dimerization-deficient

Language: Английский

Citations

109
Condensed but liquid-like domain organization of active chromatin regions in living human cells DOI Creative Commons
Tadasu Nozaki, Soya Shinkai, Satoru Ide

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(14)

Published: April 5, 2023

In eukaryotes, higher-order chromatin organization is spatiotemporally regulated as domains, for various cellular functions. However, their physical nature in living cells remains unclear (e.g., condensed domains or extended fiber loops; liquid-like solid-like). Using novel approaches combining genomics, single-nucleosome imaging, and computational modeling, we investigated the behavior of early DNA replicated regions human cells, which correspond to Hi-C contact with active marks. Motion correlation analysis two neighbor nucleosomes shows that form physically ~150-nm diameters, even regions. The mean-square displacement between demonstrates behave like a liquid domain on ~150 nm/~0.5 s spatiotemporal scale, facilitates accessibility. Beyond micrometers/minutes seems solid-like, may contribute maintaining genome integrity. Our study reveals viscoelastic principle polymer; locally dynamic reactive but globally stable.

Language: Английский

Citations

76
Single-nucleosome imaging reveals steady-state motion of interphase chromatin in living human cells DOI Creative Commons
Shiori Iida, Soya Shinkai, Yuji Itoh

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(22)

Published: June 3, 2022

Dynamic chromatin behavior plays a critical role in various genome functions. However, it remains unclear how changes during interphase, where the nucleus enlarges and genomic DNA doubles. While previously reported movements varied interphase when measured using minute or longer time scale, we unveil that local motion captured by single-nucleosome imaging/tracking on second scale remained steady throughout G 1 , S, 2 phases live human cells. This mode appeared to change beyond this scale. A defined region also behaved similarly. Combined with Brownian dynamics modeling, our results suggest steady-state was mainly driven thermal fluctuations. Steady-state temporarily increased following damage response. Our findings support viscoelastic properties of chromatin. We propose observed allows cells conduct housekeeping functions, such as transcription replication, under similar environments interphase.

Language: Английский

Citations

40
Is euchromatin really open in the cell? DOI
Kazuhiro Maeshima, Shiori Iida, Masa A. Shimazoe

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 34(1), P. 7 - 17

Published: June 27, 2023

Language: Английский

Citations

38
Toward the Development of Epigenome Editing-Based Therapeutics: Potentials and Challenges DOI Open Access
Jun Ueda, Taiga Yamazaki,

Hiroshi Funakoshi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4778 - 4778

Published: March 1, 2023

The advancement in epigenetics research over the past several decades has led to potential application of epigenome-editing technologies for treatment various diseases. In particular, epigenome editing is potentially useful genetic and other related diseases, including rare imprinted as it can regulate expression target region, thereby causative gene, with minimal or no modification genomic DNA. Various efforts are underway successfully apply vivo, such improving specificity, enzymatic activity, drug delivery development reliable therapeutics. this review, we introduce latest findings, summarize current limitations future challenges practical disease therapy, important factors consider, chromatin plasticity, a more effective editing-based therapy.

Language: Английский

Citations

33
Orientation-independent-DIC imaging reveals that a transient rise in depletion attraction contributes to mitotic chromosome condensation DOI Creative Commons
Shiori Iida, Satoru Ide, Sachiko Tamura

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(36)

Published: Aug. 27, 2024

Genomic information must be faithfully transmitted into two daughter cells during mitosis. To ensure the transmission process, interphase chromatin is further condensed mitotic chromosomes. Although protein factors like condensins and topoisomerase IIα are involved in assembly of chromosomes, physical bases condensation process remain unclear. Depletion attraction/macromolecular crowding, an effective attractive force that arises between large structures crowded environments around may contribute to process. approach this issue, we investigated “chromosome milieu” mitosis living human using orientation-independent-differential interference contrast module combined with a confocal laser scanning microscope, which capable precisely mapping optical path differences estimating molecular densities. We found density surrounding chromosomes increased progression from prophase anaphase, concurring chromosome condensation. However, went down telophase, when decondensation began. Changes by hypotonic or hypertonic treatment consistently altered levels In vitro, native was converted liquid droplets presence cations macromolecular crowder. Additional crowder made stiffer more solid-like. These results suggest transient rise depletion attraction, likely triggered relocation macromolecules (proteins, RNAs, others) via nuclear envelope breakdown subsequent decrease cell volumes, contributes condensation, shedding light on different aspect mechanism cells.

Language: Английский

Citations

11
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
Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2 DOI Creative Commons
Jonathan Lerner, Andrew Katznelson, Jingchao Zhang

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(7), P. 112748 - 112748

Published: July 1, 2023

Pioneer transcription factors interact with nucleosomes to scan silent, compact chromatin, enabling cooperative events that modulate gene activity. While at a subset of sites pioneer access chromatin by assisted loading other factors, the nucleosome-binding properties enable them initiate zygotic genome activation, embryonic development, and cellular reprogramming. To better understand nucleosome targeting in vivo, we assess whether FoxA1 Sox2 target stable or unstable find they DNase-resistant, nucleosomes, whereas HNF4A, non-nucleosome binding factor, targets open, DNase-sensitive chromatin. Despite FOXA1 SOX2 similar proportions DNase-resistant using single-molecule tracking, uses lower nucleoplasmic diffusion longer residence times while higher shorter HNF4 scans much less efficiently. Thus, through distinct processes.

Language: Английский

Citations

20
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