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Series GSE218269 Query DataSets for GSE218269
Status Public on Jun 01, 2024
Title CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Cyclin-dependent kinase 7 (CDK7), part of general transcription factor TFIIH, promotes gene transcription by phosphorylating the C-terminal domain of RNA polymerase II (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 Pol II retention at promoters, leading to decreased Pol II initiation and immediate global downregulation of transcript synthesis. Elongation, termination, and recruitment of co-transcriptional factors are not directly affected. Although Pol II, initiation factors, and Mediator accumulate at promoters, Pol II complexes can also proceed into gene bodies without promoter-proximal pausing while retaining initiation factors and Mediator. Further downstream, Pol II phosphorylation increases, initiation factors and Mediator are released, allowing recruitment of elongation factors and increase in Pol II elongation velocity. Collectively, CDK7 kinase activity promotes the release of initiation factors and Mediator from Pol II, facilitating Pol II escape from the promoter.
 
Overall design All samples were collected in biological duplicates, except MNase-ChIP-seq, for which three replicates were collected. Cells were treated for 15, 30, or 60 min with 7.5 μM of 1-NM-PP1 or an equal volume of DMSO (solvent control).
 
Contributor(s) Velychko T, Mohammad E, Ferrer-Vicens I, Parfentev I, Werner M, Studniarek C, Schwalb B, Urlaub H, Murphy S, Cramer P, Lidschreiber M
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Submission date Nov 17, 2022
Last update date Jun 01, 2024
Contact name Michael Lidschreiber
E-mail(s) michael.lidschreiber@mpinat.mpg.de
Organization name Max-Planck-Institute for Multidisciplinary Scienes
Street address Am Fassberg 11
City Goettingen
ZIP/Postal code 37077
Country Germany
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (100)
GSM6738161 HEK293CDK7as_TTseq_LabeledRNA_DMSO_15min_Rep1
GSM6738162 HEK293CDK7as_TTseq_LabeledRNA_DMSO_15min_Rep2
GSM6738163 HEK293CDK7as_TTseq_LabeledRNA_DMSO_30min_Rep1
Relations
BioProject PRJNA902829

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Supplementary file Size Download File type/resource
GSE218269_RAW.tar 15.3 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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