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Series GSE139466 Query DataSets for GSE139466
Status Public on May 11, 2020
Title Selective Mediator-dependence of cell type-specifying transcription [HiChIP]
Organism Homo sapiens
Experiment type Genome binding/occupancy 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.
Overall design H3K27ac HiChIP after 2h MED14-dTAG degradation by 500nM dTAG7 in KBM7 cells.
Contributor(s) Jaeger MG, Mackowiak SD, Hnisz D, 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 (4)
GSM4142027 H3K27ac_HiChIP_MED14-dTAG_2h_DMSO_A
GSM4142028 H3K27ac_HiChIP_MED14-dTAG_2h_DMSO_B
GSM4142029 H3K27ac_HiChIP_MED14-dTAG_2h_dTAG7_A
This SubSeries is part of SuperSeries:
GSE139468 Selective Mediator dependence of cell-type-specifying transcription
BioProject PRJNA579928
SRA SRP227193

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE139466_RAW.tar 982.8 Mb (http)(custom) TAR (of HIC)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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