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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Transcriptional architecture of the mammalian circadian clock

Nature Reviews Genetics, Journal Year: 2016, Volume and Issue: 18(3), P. 164 - 179

Published: Dec. 19, 2016

Language: Английский

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A Phase Separation Model for Transcriptional Control

Cell, Journal Year: 2017, Volume and Issue: 169(1), P. 13 - 23

Published: March 1, 2017

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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Transcriptional Addiction in Cancer

Cell, Journal Year: 2017, Volume and Issue: 168(4), P. 629 - 643

Published: Feb. 1, 2017

Language: Английский

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CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function

Cell, Journal Year: 2015, Volume and Issue: 162(4), P. 900 - 910

Published: Aug. 1, 2015

Language: Английский

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YY1 Is a Structural Regulator of Enhancer-Promoter Loops

Cell, Journal Year: 2017, Volume and Issue: 171(7), P. 1573 - 1588.e28

Published: Dec. 1, 2017

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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Super-resolution imaging reveals distinct chromatin folding for different epigenetic states

Nature, Journal Year: 2016, Volume and Issue: 529(7586), P. 418 - 422

Published: Jan. 1, 2016

Language: Английский

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The Mediator complex: a central integrator of transcription

Nature Reviews Molecular Cell Biology, Journal Year: 2015, Volume and Issue: 16(3), P. 155 - 166

Published: Feb. 18, 2015

Language: Английский

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