PXD063563

PXD063563 is an original dataset announced via ProteomeXchange.

Title	Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3'-ends
Description	CDK7 regulates RNA polymerase II (RNAPII) initiation, elongation, and termination through incompletely understood mechanisms. Because contaminating kinases precluded CDK7 analysis with nuclear extracts, we completed biochemical assays with purified factors. Reconstitution of RNAPII transcription initiation showed CDK7 inhibition slowed and/or paused RNAPII promoterproximal transcription, which reduced re-initiation. These CDK7-regulatory functions were Mediator- and TFIID-dependent. Similarly in human cells, CDK7 inhibition reduced transcription by suppressing RNAPII activity at promoters, consistent with reduced initiation and/or re-initiation. Moreover, widespread 3'-end readthrough transcription was observed in CDK7-inhibited cells; mechanistically, this occurred through rapid nuclear depletion of RNAPII elongation and termination factors, including high-confidence CDK7 targets. Collectively, these results define how CDK7 governs RNAPII function at gene 5'-ends and 3'-ends, and reveal that nuclear abundance of elongation and termination factors is kinase-dependent. Because 3'-readthrough transcription is commonly induced during stress, our results further suggest regulated suppression of CDK7 activity may enable this RNAPII transcriptional response.
HostingRepository	PRIDE
AnnounceDate	2025-05-08
AnnouncementXML	Submission_2025-05-08_15:02:10.807.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD063563
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Ebmeier
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-02 08:17:54	ID requested
⏵ 1	2025-05-08 15:02:11	announced

10.6019/PXD063563;

10.1101/2025.01.08.632016;

submitter keyword: CDK7 regulates RNAPII

Dylan J Taatjes
contact affiliation	Professor
contact email	dylan.taatjes@colorado.edu
lab head
Christopher Ebmeier
contact affiliation	University of Colorado Boulder
contact email	christopher.ebmeier@colorado.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063563
     1. Label: PRIDE project
     2. Name: Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3'-ends