PXD017611-1

PXD017611 is an original dataset announced via ProteomeXchange.

Title	Mechanistic basis for selective Mediator-dependence of cell type-specifying transcription
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_13:44:33.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin Jaeger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-19 01:50:52	ID requested
⏵ 1	2021-09-08 13:44:34	announced
2	2024-10-22 05:26:39	announced	2024-10-22: Updated project metadata.

Jaeger MG, Schwalb B, Mackowiak SD, Velychko T, Hanzl A, Imrichova H, Brand M, Agerer B, Chorn S, Nabet B, Ferguson FM, M, ü, 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]

submitter keyword: chromatin proteomics, chromatome, human, LUMOS

Georg E. Winter
contact affiliation	Winter Lab, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
contact email	gwinter@cemm.oeaw.ac.at
lab head
Martin Jaeger
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	mjaeger@cemm.oeaw.ac.at
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD017611

PRIDE project URI

• PRIDE
  1. PXD017611
     1. Label: PRIDE project
     2. Name: Mechanistic basis for selective Mediator-dependence of cell type-specifying transcription