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A TBP-independent mechanism for RNA Polymerase II transcription

View ORCID ProfileJames Z.J. Kwan, View ORCID ProfileThomas F. Nguyen, View ORCID ProfileMarek A. Budzyński, Jieying Cui, Rachel M. Price, View ORCID ProfileSheila S. Teves
doi: https://doi.org/10.1101/2021.03.28.437425
James Z.J. Kwan
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC V6T 1Z3, Canada
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Thomas F. Nguyen
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC V6T 1Z3, Canada
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Marek A. Budzyński
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC V6T 1Z3, Canada
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Jieying Cui
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC V6T 1Z3, Canada
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Rachel M. Price
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC V6T 1Z3, Canada
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Sheila S. Teves
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC V6T 1Z3, Canada
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  • For correspondence: sheila.teves@ubc.ca
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Abstract

Transcription by RNA Polymerase II (Pol II) is initiated by the hierarchical assembly of the Pre-Initiation Complex onto promoter DNA. Decades of in vitro and yeast research have shown that the TATA-box binding protein (TBP) is essential to Pol II initiation by triggering the binding of other general transcription factors, and ensuring proper Pol II loading. Here, we report instead that acute depletion of TBP in mouse embryonic stem cells (mESCs) has no global effect on ongoing Pol II transcription. Surprisingly, Pol II transcriptional induction through the Heat Shock Response or cellular differentiation also occurs normally in the absence of TBP. In contrast, acute TBP depletion severely impairs initiation by RNA Polymerase III. Lastly, we show that a metazoan-specific paralog of TBP is expressed in mESCs and that it binds to promoter regions of active Pol II genes even in the absence of TBP. Taken together, our findings reveal an unexplored TBP-independent process in mESCs that points to a diversity in Pol II transcription initiation mechanisms.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted March 29, 2021.
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A TBP-independent mechanism for RNA Polymerase II transcription
James Z.J. Kwan, Thomas F. Nguyen, Marek A. Budzyński, Jieying Cui, Rachel M. Price, Sheila S. Teves
bioRxiv 2021.03.28.437425; doi: https://doi.org/10.1101/2021.03.28.437425
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A TBP-independent mechanism for RNA Polymerase II transcription
James Z.J. Kwan, Thomas F. Nguyen, Marek A. Budzyński, Jieying Cui, Rachel M. Price, Sheila S. Teves
bioRxiv 2021.03.28.437425; doi: https://doi.org/10.1101/2021.03.28.437425

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