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Status |
Public on Oct 26, 2018 |
Title |
Transcription factors activate genes through the phase separation capacity of their activation domains [RNA-seq] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well- characterized, but little is known about the mechanisms by which ADs effect gene activation. Here we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation.
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Overall design |
RNA-seq in mouse embryonic stem cells after OCT4 degradation or LIF withdrawal
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Contributor(s) |
Boija A, Klein IA, Sabari BR, Dall'Agnese A, Coffey EL, Zamudio AV, Li CH, Shrinivas K, Manteiga JC, Hannett NM, Abraham BJ, Afeyan LK, Gouo YE, Rimel JK, Fant CB, Schuijers J, Lee TI, Taatjes DJ, Young RA |
Citation(s) |
30449618 |
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Submission date |
Sep 25, 2018 |
Last update date |
Mar 21, 2019 |
Contact name |
Richard A Young |
E-mail(s) |
young_computation@wi.mit.edu
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Phone |
617-258-5219
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Organization name |
Whitehead Institute for Biomedical Research
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Lab |
Young Lab
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Street address |
9 Cambridge Center
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (8)
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This SubSeries is part of SuperSeries: |
GSE120476 |
Transcription factors activate genes through the phase separation capacity of their activation domains |
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Relations |
BioProject |
PRJNA493115 |
SRA |
SRP162582 |