PXD037842-1

PXD037842 is an original dataset announced via ProteomeXchange.

Title	CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release
Description	Cyclin-dependent kinase 7 (CDK7), part of the general transcription factor TFIIH, promotes gene transcription by phosphorylating the C-terminal domain of RNA polymerase II (RNA Pol II). Here, we combine rapid CDK7 kinase inhibition with multi-omics analysis to unravel the direct functions of CDK7 in human cells. CDK7 inhibition causes RNA Pol II retention at promoters, leading to decreased RNA Pol II initiation and immediate global downregulation of transcript synthesis. Elongation, termination, and recruitment of co-transcriptional factors are not directly affected. Although RNA Pol II, initiation factors, and Mediator accumulate at promoters, RNA Pol II complexes can also proceed into gene bodies without promoter-proximal pausing while retaining initiation factors and Mediator. Further downstream, RNA Pol II phosphorylation increases and initiation factors and Mediator are released, allowing recruitment of elongation factors and an increase in RNA Pol II elongation velocity. Collectively, CDK7 kinase activity promotes the release of initiation factors and Mediator from RNA Pol II, facilitating RNA Pol II escape from the promoter.
HostingRepository	PRIDE
AnnounceDate	2024-05-31
AnnouncementXML	Submission_2024-05-30_23:48:22.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Taras Velychko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-31 09:04:13	ID requested
⏵ 1	2024-05-30 23:48:22	announced
2	2024-10-22 06:43:22	announced	2024-10-22: Updated project metadata.

10.1016/J.MOLCEL.2024.05.007;

submitter keyword: Phosphoproteomics,TMT

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077 Göttingen, Germany Bioanalytics, Institute of Clinical Chemistry, University Medical Center Göttingen, 37075 Göttingen, Germany
contact email	henning.urlaub@mpinat.mpg.de
lab head
Taras Velychko
contact affiliation	Max Planck Institute for Multidisciplinary Sciences
contact email	taras.velychko@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037842
     1. Label: PRIDE project
     2. Name: CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release