Mechanics and functional consequences of nuclear deformations

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(9), P. 583 - 602

Published: May 5, 2022

Language: Английский

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Coaching from the sidelines: the nuclear periphery in genome regulation

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 20(1), P. 39 - 50

Published: Oct. 24, 2018

Language: Английский

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Chromatin alternates between A and B compartments at kilobase scale for subgenic organization

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

Published: June 6, 2023

Abstract Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops generally studied a finer scale, the impact looping on proximal interactions remains enigmatic. Here, we critically examine nuclear and loop-proximal using combination in situ Hi-C unparalleled depth, algorithm development, biophysical modeling. Producing large map with 33 billion contacts conjunction an for performing principal component analysis sparse, super massive matrices (POSSUMM), resolve to 500 bp. Our results demonstrate that essentially all active promoters distal enhancers localize A compartment, even when flanking sequences do not. Furthermore, find TSS TTS paused genes often segregated into separate compartments. We then identify diffuse radiate from loop anchors, which correlate strong enhancer-promoter transcription. also these depend CTCF’s RNA binding domains. In this work, fine-scale organization consistent revised model more precise than commonly thought while protracted.

Language: Английский

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An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: Jan. 23, 2023

Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via silencing. Unlike many histone modifications chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human types, which limits our understanding role peripheral plays development disease.

Language: Английский

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The impact of DNA methylation on CTCF-mediated 3D genome organization

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(3), P. 404 - 412

Published: March 1, 2024

Language: Английский

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Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(5), P. 938 - 954.e9

Published: Feb. 1, 2021

Language: Английский

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Nuclear Compartments: An Incomplete Primer to Nuclear Compartments, Bodies, and Genome Organization Relative to Nuclear Architecture

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(7), P. a041268 - a041268

Published: Aug. 16, 2021

This work reviews nuclear compartments, defined broadly to include distinct structures, bodies, and chromosome domains. It first summarizes original cytological observations before comparing concepts of compartments emerging from microscopy versus genomic approaches then introducing new multiplexed imaging that promise in the future meld both approaches. I discuss how previous models radial distribution chromosomes or binary division genome into A B are now being refined by recognition more complex compartmentalization. The poorly understood question these established maintained is discussed, including through modern perspective phase separation, moving on address possible functions using role speckles modulating gene expression as an example. Finally, review concludes with a discussion questions for this field.

Language: Английский

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Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

Protein & Cell, Journal Year: 2020, Volume and Issue: 13(4), P. 258 - 280

Published: Nov. 5, 2020

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and remains poorly understood. Here by combining imaging sequencing, we studied role of lamin B1 in dynamics. We found that depletion leads to detachment lamina-associated domains (LADs) from nuclear periphery global redistribution decompaction. Consequently, inter-chromosomal as well inter-compartment interactions are increased, but structure topologically associating (TADs) not affected. Using live-cell genomic loci tracking, further proved increased dynamics, owing decompaction toward nucleoplasm. Taken together, our data suggest at promote LAD maintenance, compaction, compartmentalization chromosome territories A/B compartments confine supporting their crucial roles

Language: Английский

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Live imaging of chromatin distribution reveals novel principles of nuclear architecture and chromatin compartmentalization

Science Advances, Journal Year: 2021, Volume and Issue: 7(23)

Published: June 2, 2021

Live imaging of chromatin in an intact organism reveals a novel mode mesoscale organization at nuclear periphery.

Language: Английский

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Mesoscale phase separation of chromatin in the nucleus

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

Published: May 4, 2021

Intact-organism imaging of Drosophila larvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer nuclear envelope, conventionally fill nucleus, centrally, or as a wetting droplet. These transitions are controlled by changes in volume interaction with (part envelope) at periphery. Using simple polymeric model that includes key features self-attraction its binding to lamina, we demonstrate theoretically it is competition these two effects determines mode distribution. qualitative trends well composition profiles obtained our simulations compare observed intact-organism quantification. Since contain only small number physical variables identify generic mechanisms underlying separations.

Language: Английский

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