Methods for mapping 3D-chromosome architecture around nucleoli DOI Creative Commons
Cristiana Bersaglieri, Raffaella Santoro

Current Opinion in Cell Biology, Journal Year: 2023, Volume and Issue: 81, P. 102171 - 102171

Published: April 1, 2023

The nucleolus is the largest subcompartment of nucleus, known to be place ribosome biogenesis. Emerging evidence has started implicate in organization chromosomes nucleus. Genomic domains contacting are defined as nucleolar associated (NADs) and generally characterized by repressive chromatin states. However, role genome architecture remains still not fully understood mainly because lack a membrane challenged establishment methods for accurate identification NADs. Here, we will discuss recent advances on identify characterize NADs, their improvements relative old methods, highlight future perspectives.

Language: Английский

Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance DOI Open Access
Jan Padeken, Stephen P. Methot, Susan M. Gasser

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(9), P. 623 - 640

Published: May 13, 2022

Language: Английский

Citations

312
Chromatin accessibility: methods, mechanisms, and biological insights DOI Creative Commons
Andrés Mansisidor, Viviana I. Risca

Nucleus, Journal Year: 2022, Volume and Issue: 13(1), P. 238 - 278

Published: Nov. 20, 2022

Access to DNA is a prerequisite the execution of essential cellular processes that include transcription, replication, chromosomal segregation, and repair. How proteins regulate these function in context chromatin its dynamic architectures an intensive field study. Over past decade, genome-wide assays new imaging approaches have enabled greater understanding how access genome regulated by nucleosomes associated proteins. Additional mechanisms may control accessibility vivo compaction phase separation – are beginning be understood. Here, we review ongoing development measurements, summarize different molecular structural shape landscape, detail many important biological functions linked accessibility.

Language: Английский

Citations

73
Lamins: The backbone of the nucleocytoskeleton interface DOI Creative Commons

Joan M. Sobo,

Nicholas S. Alagna,

Sean X. Sun

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 86, P. 102313 - 102313

Published: Jan. 22, 2024

Language: Английский

Citations

20
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
Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation DOI

Jagdish Mishra,

Subhajit Chakraborty,

Niharika Niharika

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 12, 2024

Abstract Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in cell's physical surroundings. These of impose mechanical tension intracellular protein network (both cytosolic nuclear). could released by series protein–protein interactions often facilitated membrane lipids, lectins sugar molecules thus generate type signal drive cellular processes, including differentiation, polarity, growth, adhesion, movement, survival. Recent experimental data have accentuated molecular mechanism this transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins plasma discern channel information interior. Cells respond message altering their arrangement directly transmitting nucleus through connection cytoskeleton nucleoskeleton before despatched biochemical signaling pathways. Nuclear transmission force leads activation chromatin modifiers modulation epigenetic landscape, inducing reorganization gene expression regulation; time chemical messengers (transcription factors) arrive into nucleus. While significant research has been done on role mechanotransduction tumor development cancer progression/metastasis, mechanistic basis force‐activated carcinogenesis is still enigmatic. Here, review, we discussed various cues connections better comprehend also explored detailed some multiple players (proteins macromolecular complexes) involved Thus, described an avenue: how stress directs modulate epigenome cells aberrant phenotype.

Language: Английский

Citations

9
Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization DOI Creative Commons
Aayush Kant, Zixian Guo,

Vinayak Vinayak

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 21, 2024

Abstract In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, modifications, extrusion. predict that heterochromatic governed by balance among diffusive flux methylated histones sustaining them acetylation reactions in process loop extrusion via supercoiling RNAPII at their periphery, which contributes to reduction. Super-resolution nano-imaging five distinct cell lines confirm predictions indicating absence leads larger heterochromatin domains. Furthermore, accurately reproduces findings regarding how transcription-mediated loss can mitigate impacts excessive cohesin loading. Our shed light role genome organization, offering insights into dynamics potential therapeutic targets.

Language: Английский

Citations

9
Phase Separation and Correlated Motions in Motorized Genome DOI
Zhongling Jiang, Yifeng Qi, Kartik Kamat

et al.

The Journal of Physical Chemistry B, Journal Year: 2022, Volume and Issue: 126(30), P. 5619 - 5628

Published: July 20, 2022

The human genome is arranged in the cell nucleus nonrandomly, and phase separation has been proposed as an important driving force for organization. However, active system, contribution of nonequilibrium activities to structure dynamics remains be explored. We simulated using energy function parametrized with chromosome conformation capture (Hi-C) data presence active, nondirectional forces that break detailed balance. found may arise from transcription chromatin remodeling can dramatically impact spatial localization heterochromatin. When applied euchromatin, drive heterochromatin nuclear envelope compete passive interactions among tend pull them opposite directions. Furthermore, induce long-range correlations genomic loci beyond single territories. further showed could understood effective temperature defined fluctuation-dissipation ratio. Our study suggests significantly dynamics, producing unexpected collective phenomena.

Language: Английский

Citations

29
The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation DOI Open Access
Fumihiko Nakamura

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2135 - 2135

Published: Feb. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

Language: Английский

Citations

8
Constricted migration is associated with stable 3D genome structure differences in cancer cells DOI Open Access
Rosela Golloshi, Christopher Playter,

Trevor F. Freeman

et al.

EMBO Reports, Journal Year: 2022, Volume and Issue: 23(10)

Published: Aug. 15, 2022

Language: Английский

Citations

25
The Molecular and Cellular Basis of Hutchinson–Gilford Progeria Syndrome and Potential Treatments DOI Open Access

Noelle J. Batista,

Sanket G. Desai,

Alexis M. Perez

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(3), P. 602 - 602

Published: Feb. 27, 2023

Hutchinson–Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome. HGPS most often derived from de novo point mutation in the LMNA gene, which results an alternative splicing defect generation of mutant protein, progerin. Progerin behaves dominant-negative fashion, leading to variety cellular molecular changes, including nuclear abnormalities, defective DNA damage response (DDR) repair, accelerated telomere attrition. Intriguingly, many manifestations cells are shared with normal cells. However, at clinical level, does not fully match because nature phenotypes its primary effects on connective tissues. Furthermore, epigenetic changes patients great interest may play crucial role pathogenesis HGPS. Finally, various treatments for have been developed recent years important translate symptomatic improvement increased lifespan.

Language: Английский

Citations

15