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Evolution of promoter-proximal pausing enabled a new layer of transcription control

Alexandra G. Chivu, View ORCID ProfileAbderhman Abuhashem, Gilad Barshad, Edward J. Rice, Michelle M. Leger, Albert C. Vill, Wilfred Wong, Rebecca Brady, View ORCID ProfileJeramiah J. Smith, Athula H. Wikramanayake, César Arenas-Mena, Ilana L. Brito, Iñaki Ruiz-Trillo, Anna-Katerina Hadjantonakis, John T. Lis, James J. Lewis, View ORCID ProfileCharles G. Danko
doi: https://doi.org/10.1101/2023.02.19.529146
Alexandra G. Chivu
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
2Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY 14853, USA
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Abderhman Abuhashem
4Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, NY 10065, USA
5Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, NY 10065, USA
6Biochemistry Cell and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, NY 10065, USA
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  • ORCID record for Abderhman Abuhashem
Gilad Barshad
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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Edward J. Rice
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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Michelle M. Leger
10Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Barcelona, 08003, Spain
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Albert C. Vill
2Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY 14853, USA
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Wilfred Wong
13Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
14Tri-Institutional training Program in Computational Biology and Medicine, New York, NY 10065, USA
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Rebecca Brady
16Department of Biology, Ithaca College, Ithaca NY 14850, USA
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Jeramiah J. Smith
9Department of Biology, University of Kentucky, Lexington, KY, 40506, USA
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Athula H. Wikramanayake
15Department of Biology, University of Miami, Coral Gables, FL 33146
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César Arenas-Mena
7Department of Biology at the College of Staten Island and PhD Programs in Biology and Biochemistry at The Graduate Center, The City University of New York (CUNY), Staten Island, NY 10314, USA
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Ilana L. Brito
12Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA
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Iñaki Ruiz-Trillo
10Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Barcelona, 08003, Spain
11ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain., Barcelona, 08003, Spain
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Anna-Katerina Hadjantonakis
4Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, NY 10065, USA
6Biochemistry Cell and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, NY 10065, USA
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John T. Lis
2Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY 14853, USA
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  • For correspondence: dankoc@gmail.com jtl10@cornell.edu jjl8@clemson.edu
James J. Lewis
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
8Department of Genetics and Biochemistry, Clemson University, 105 Collings St, Clemson, SC 29634
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  • For correspondence: dankoc@gmail.com jtl10@cornell.edu jjl8@clemson.edu
Charles G. Danko
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
3Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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  • ORCID record for Charles G. Danko
  • For correspondence: dankoc@gmail.com jtl10@cornell.edu jjl8@clemson.edu
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Abstract

Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. To understand the evolution and function of pausing, we analyzed transcription in 20 organisms across the tree of life. Unicellular eukaryotes have a slow acceleration of Pol II near transcription start sites that matured into a longer and more focused pause in metazoans. Increased pause residence time coincides with the evolution of new subunits in the NELF and 7SK complexes. In mammals, depletion of NELF reverts a focal pause to a proto-paused-like state driven in part by DNA sequence. Loss of this focal pause compromises transcriptional activation for a set of heat shock genes. Overall, we discovered how pausing evolved and increased regulatory complexity in metazoans.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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 4.0 International license.
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Posted February 19, 2023.
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Evolution of promoter-proximal pausing enabled a new layer of transcription control
Alexandra G. Chivu, Abderhman Abuhashem, Gilad Barshad, Edward J. Rice, Michelle M. Leger, Albert C. Vill, Wilfred Wong, Rebecca Brady, Jeramiah J. Smith, Athula H. Wikramanayake, César Arenas-Mena, Ilana L. Brito, Iñaki Ruiz-Trillo, Anna-Katerina Hadjantonakis, John T. Lis, James J. Lewis, Charles G. Danko
bioRxiv 2023.02.19.529146; doi: https://doi.org/10.1101/2023.02.19.529146
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Evolution of promoter-proximal pausing enabled a new layer of transcription control
Alexandra G. Chivu, Abderhman Abuhashem, Gilad Barshad, Edward J. Rice, Michelle M. Leger, Albert C. Vill, Wilfred Wong, Rebecca Brady, Jeramiah J. Smith, Athula H. Wikramanayake, César Arenas-Mena, Ilana L. Brito, Iñaki Ruiz-Trillo, Anna-Katerina Hadjantonakis, John T. Lis, James J. Lewis, Charles G. Danko
bioRxiv 2023.02.19.529146; doi: https://doi.org/10.1101/2023.02.19.529146

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