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Series GSE139461 Query DataSets for GSE139461
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.
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.
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)
GSM4141917 CDK9_DMSO_A
GSM4141918 CDK9_DMSO_B
GSM4141919 CDK9_DMSO_C
This SubSeries is part of SuperSeries:
GSE139468 Selective Mediator dependence of cell-type-specifying transcription
BioProject PRJNA579917
SRA SRP227188

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
GSE139461_MB-18-56_Quant-seq_loess_norm_count_table.txt.gz 4.9 Mb (ftp)(http) TXT
GSE139461_MB-18-56_Quant-seq_raw_count_table.txt.gz 1.1 Mb (ftp)(http) TXT
GSE139461_RAW.tar 2.0 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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