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The pause-initiation limit restricts transcription activation in human cells

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  • Saskia Gressel

    (Max-Planck-Institute for Biophysical Chemistry)

  • Björn Schwalb

    (Max-Planck-Institute for Biophysical Chemistry)

  • Patrick Cramer

    (Max-Planck-Institute for Biophysical Chemistry)

Abstract

Eukaryotic gene transcription is often controlled at the level of RNA polymerase II (Pol II) pausing in the promoter-proximal region. Pausing Pol II limits the frequency of transcription initiation (‘pause-initiation limit’), predicting that the pause duration must be decreased for transcriptional activation. To test this prediction, we conduct a genome-wide kinetic analysis of the heat shock response in human cells. We show that the pause-initiation limit restricts transcriptional activation at most genes. Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. The transcription of enhancer elements is generally not pause limited and can be activated without CDK9 activity. Our results define the kinetics of Pol II transcriptional regulation in human cells at all gene classes during a natural transcription response.

Suggested Citation

  • Saskia Gressel & Björn Schwalb & Patrick Cramer, 2019. "The pause-initiation limit restricts transcription activation in human cells," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11536-8
    DOI: 10.1038/s41467-019-11536-8
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    Cited by:

    1. Negin Khosraviani & V. Talya Yerlici & Jonathan St-Germain & Yi Yang Hou & Shi Bo Cao & Carla Ghali & Michael Bokros & Rehna Krishnan & Razqallah Hakem & Stephen Lee & Brian Raught & Karim Mekhail, 2024. "Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Michael DeBerardine & Gregory T. Booth & Philip P. Versluis & John T. Lis, 2023. "The NELF pausing checkpoint mediates the functional divergence of Cdk9," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Vivekanandan Ramalingam & Xinyang Yu & Brian D. Slaughter & Jay R. Unruh & Kaelan J. Brennan & Anastasiia Onyshchenko & Jeffrey J. Lange & Malini Natarajan & Michael Buck & Julia Zeitlinger, 2023. "Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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