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PXD017611 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMechanistic basis for selective Mediator-dependence of cell type-specifying transcription
DescriptionThe Mediator complex routes signals from DNA-binding transcription factors to RNA polymerase (Pol) II. Despite its 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. Remarkably, 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMartin Jaeger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-02-19 01:50:52ID requested
12021-09-08 13:44:34announced
Publication List
Jaeger MG, Schwalb B, Mackowiak SD, Velychko T, Hanzl A, Imrichova H, Brand M, Agerer B, Chorn S, Nabet B, Ferguson FM, M, ΓΌ, ller AC, Bergthaler A, Gray NS, Bradner JE, Bock C, Hnisz D, Cramer P, Winter GE, Selective Mediator dependence of cell-type-specifying transcription. Nat Genet, 52(7):719-727(2020) [pubmed]
Keyword List
submitter keyword: chromatin proteomics, chromatome, human, LUMOS
Contact List
Georg E. Winter
contact affiliationWinter Lab, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
contact emailgwinter@cemm.oeaw.ac.at
lab head
Martin Jaeger
contact affiliationCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact emailmjaeger@cemm.oeaw.ac.at
dataset submitter
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Dataset FTP location
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