|
| Status |
Public on May 11, 2020 |
| Title |
Selective Mediator-dependence of cell type-specifying transcription [Quant-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The Mediator complex directs signals from DNA-binding transcription factors to RNA polymerase (Pol) II. Despite this pivotal position, mechanistic understanding of Mediator in human cells remains incomplete. Here, we quantified Mediator-controlled Pol II kinetics by coupling rapid subunit degradation with orthogonal experimental readouts. Consistent with a model of condensate-driven transcription initiation, large clusters of hypo-phosphorylated Pol II rapidly disassembled upon Mediator degradation. This was accompanied by a selective and pronounced disruption of cell type-specifying transcriptional circuits, whose constituent genes featured exceptionally high rates of Pol II turnover. Notably, transcriptional output of most other genes was largely unaffected by acute Mediator ablation. Maintenance of transcriptional activity at these genes was linked to an unexpected, CDK9-dependent compensatory feedback loop that elevated Pol II pause release rates genome-wide. Collectively, our work positions human Mediator as a globally acting coactivator that selectively safeguards the functionality of cell type-specifying transcriptional networks.
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| |
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| Overall design |
Quant-seq (3' mRNA-seq) in engineered and wild-type KBM7 cells after 6h treatments with DMSO, 500nM dTAG7, 250nM THAL-SNS-032 (dCDK9), or 100nM dBET6.
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| |
|
| Contributor(s) |
Jaeger MG, Brand M, Winter GE |
| Citation(s) |
32483291 |
| Submission date |
Oct 28, 2019 |
| Last update date |
Aug 17, 2020 |
| Contact name |
Georg E Winter |
| Organization name |
CeMM - Research Institute for Molecular Medicine of the Austrian Academy of Sciences
|
| Street address |
Lazarettgasse 14, AKH BT25.3
|
| City |
Wien |
| State/province |
Austria |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (66)
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| This SubSeries is part of SuperSeries: |
| GSE139468 |
Selective Mediator dependence of cell-type-specifying transcription |
|
| Relations |
| BioProject |
PRJNA579917 |
| SRA |
SRP227188 |
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