Liquid phase condensation in cell physiology and disease

Science, Journal Year: 2017, Volume and Issue: 357(6357)

Published: Sept. 21, 2017

Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets protein, RNA, other biomolecules, which form absence delimiting membrane. Recent studies elucidated many aspects molecular interactions underlying these remarkable way such dictate their material properties, composition, behavior. Here, we review exciting developments highlight remaining challenges, particularly ability liquid condensates both facilitate respond biological function how metastability may underlie devastating protein aggregation diseases.

Language: Английский

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Coactivator condensation at super-enhancers links phase separation and gene control

Science, Journal Year: 2018, Volume and Issue: 361(6400)

Published: June 21, 2018

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density the transcriptional apparatus to drive robust expression genes with prominent roles in cell identity. Here we demonstrate SE-enriched coactivators BRD4 and MED1 form nuclear puncta at SEs exhibit properties liquid-like condensates disrupted by chemicals perturb condensates. The intrinsically disordered regions (IDRs) can phase-separated droplets, MED1-IDR droplets compartmentalize concentrate transcription from extracts. These results support idea apparatus, suggest role for coactivator IDRs this process, offer insights into mechanisms involved control key cell-identity genes.

Language: Английский

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Cohesin Loss Eliminates All Loop Domains

Cell, Journal Year: 2017, Volume and Issue: 171(2), P. 305 - 320.e24

Published: Oct. 1, 2017

Language: Английский

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Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains

Cell, Journal Year: 2018, Volume and Issue: 175(7), P. 1842 - 1855.e16

Published: Nov. 15, 2018

Language: Английский

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Mediator and RNA polymerase II clusters associate in transcription-dependent condensates

Science, Journal Year: 2018, Volume and Issue: 361(6400), P. 412 - 415

Published: June 21, 2018

Models of gene control have emerged from genetic and biochemical studies, with limited consideration the spatial organization dynamics key components in living cells. We used live-cell superresolution light-sheet imaging to study Mediator coactivator RNA polymerase II (Pol II) directly. Pol each form small transient large stable clusters embryonic stem are colocalized clusters, which associate chromatin, properties phase-separated condensates, sensitive transcriptional inhibitors. suggest that Mediator, recruited by transcription factors at or clustered enhancer elements, interact condensates vivo.

Language: Английский

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Long non-coding RNAs: definitions, functions, challenges and recommendations

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(6), P. 430 - 447

Published: Jan. 3, 2023

Language: Английский

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Organizational principles of 3D genome architecture

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 19(12), P. 789 - 800

Published: Oct. 26, 2018

Language: Английский

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Long-range enhancer–promoter contacts in gene expression control

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(8), P. 437 - 455

Published: May 13, 2019

Language: Английский

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Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells

Science, Journal Year: 2018, Volume and Issue: 362(6413)

Published: Oct. 26, 2018

The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method tracing with kilobase- and nanometer-scale resolution, unveiling conformation across topologically associating domains (TADs) in thousands individual cells. Our data revealed TAD-like structures globular sharp domain boundaries single varied from cell to cell, occurring nonzero probabilities at all genomic positions but preferentially CCCTC-binding factor (CTCF)- cohesin-binding sites. Notably, cohesin depletion, which abolished TADs the population-average level, did not diminish cells eliminated preferential boundary positions. Moreover, we observed widespread, cooperative, multiway interactions, remained after depletion. These results provide critical insight into mechanisms underlying hub formation.

Language: Английский

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Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin

Cell, Journal Year: 2020, Volume and Issue: 183(4), P. 1103 - 1116.e20

Published: Oct. 23, 2020

Language: Английский

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