Long-distance association of topological boundaries through nuclear condensates

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(32)

Published: Aug. 1, 2022

The eukaryotic genome is partitioned into distinct topological domains separated by boundary elements. Emerging data support the concept that several well-established nuclear compartments are ribonucleoprotein condensates assembled through physical process of phase separation. Here, based on our demonstration chemical disruption condensate assembly weakens insulation properties a specific subset (∼20%) topologically associated domain (TAD) boundaries, we report disrupted boundaries characterized high level transcription and striking spatial clustering. These regions tend to be spatially associated, even interchromosomally, segregate with speckles, harbor “housekeeping” genes widely expressed in diverse cell types. observations reveal previously unappreciated mode organization mediated conserved elements harboring highly units transcriptional condensates.

Language: Английский

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Phase Separation: Direct and Indirect Driving Force for High-Order Chromatin Organization

Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 499 - 499

Published: Feb. 15, 2023

The multi-level spatial chromatin organization in the nucleus is closely related to activity. mechanism of and remodeling attract much attention. Phase separation describes biomolecular condensation which basis for membraneless compartments cells. Recent research shows that phase a key aspect drive high-order structure remodeling. In addition, functional compartmentalization formed by also plays an important role overall structure. this review, we summarized latest work about organization, focusing on direct indirect effects 3D its impact transcription regulation.

Language: Английский

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Photobody formation spatially segregates two opposing phytochrome B signaling actions of PIF5 degradation and stabilization

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

Published: April 25, 2024

Abstract Photoactivation of the plant photoreceptor and thermosensor phytochrome B (PHYB) triggers its condensation into subnuclear membraneless organelles named photobodies (PBs). However, function PBs in PHYB signaling remains frustratingly elusive. Here, we found that recruits PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) to PBs. Surprisingly, exerts opposing roles degrading stabilizing PIF5. Perturbing PB size by overproducing provoked a biphasic PIF5 response: while moderate increase enhanced degradation, further elevating level stabilized retaining more it enlarged Conversely, reducing dim light, which dynamics nucleoplasmic PIF5, switched balance towards degradation. Together, these results reveal formation spatially segregates two antagonistic actions – stabilization degradation surrounding nucleoplasm could enable an environmentally sensitive, counterbalancing mechanism titrate environmental responses.

Language: Английский

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Beyond A and B Compartments: how major nuclear locales define nuclear genome organization and function

Published: July 16, 2024

Models of nuclear genome organization often propose a binary division into active versus inactive compartments, yet they overlook bodies. Here we integrated analysis sequencing and image-based data to compare in four human cell types relative three different locales: the lamina, speckles, nucleoli. Whereas gene expression correlates mostly with speckle proximity, DNA replication timing proximity multiple locales. Speckle attachment regions emerge as initiation zones whose composition vary their frequency. Most facultative LADs retain partially repressed state iLADs, despite positioning interior. Knock out two lamina proteins, Lamin A LBR, causes shift H3K9me3-enriched from nucleolus, reciprocal relocation H3K27me3-enriched iLADs nucleolus lamina. Thus, these appear compete for consequences timing. The adherent cells is polarized bodies genomic segregating both radially equatorial plane. Together, our results underscore importance considering locales more complete understanding spatial functional genome.

Language: Английский

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Nuclear speckle biology: At the cross-roads of discovery and functional analysis

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 91, P. 102438 - 102438

Published: Sept. 27, 2024

Language: Английский

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