CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating 
initiation factor release

Velychko, Taras; Mohammad, Eusra; Ferrer-Vicens, Ivan; Parfentev, Iwan; Werner, Marcel; Studniarek, Cecilia; Schwalb, Björn; Urlaub, Henning; Murphy, Shona; Cramer, Patrick; Lidschreiber, Michael

doi:10.1016/j.molcel.2024.05.007

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学術論文

CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release

MPS-Authors

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Velychko, Taras
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons251026

Mohammad, Eusra
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons217429

Parfentev, Iwan
Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons298753

Werner, Marcel
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons173057

Schwalb, Björn
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons15947

Urlaub, Henning
Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons127020

Cramer, Patrick
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons146864

Lidschreiber, Michael
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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引用

Velychko, T., Mohammad, E., Ferrer-Vicens, I., Parfentev, I., Werner, M., Studniarek, C., Schwalb, B., Urlaub, H., Murphy, S., Cramer, P., & Lidschreiber, M. (2024). CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release. Molecular Cell, 84(12), 2287-2303.e10. doi:10.1016/j.molcel.2024.05.007.

引用: https://hdl.handle.net/21.11116/0000-000F-5BE6-8

要旨

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.