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RNA polymerase II and PARP1 shape enhancer-promoter contacts

View ORCID ProfileGilad Barshad, James J. Lewis, View ORCID ProfileAlexandra G. Chivu, View ORCID ProfileAbderhman Abuhashem, View ORCID ProfileNils Krietenstein, Edward J. Rice, View ORCID ProfileOliver J. Rando, View ORCID ProfileAnna-Katerina Hadjantonakis, View ORCID ProfileCharles G. Danko
doi: https://doi.org/10.1101/2022.07.07.499190
Gilad Barshad
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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James J. Lewis
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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Alexandra G. Chivu
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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Abderhman Abuhashem
2Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
3Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10065
4Biochemistry Cell and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA
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Nils Krietenstein
5The Novo Nordisk Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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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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Oliver J. Rando
6Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
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Anna-Katerina Hadjantonakis
2Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4Biochemistry Cell and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA
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Charles G. Danko
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
7Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
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  • For correspondence: dankoc@gmail.com
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Abstract

How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we studied enhancer-promoter contact architecture and communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription, and perturbations to transcription-associated proteins and thousands of candidate enhancers. Contact frequency between functionally validated enhancer-promoter pairs was most enriched near the +1 and +2 nucleosomes at enhancers and target promoters, indicating that functional enhancer-promoter pairs spend time in close physical proximity. Blocking RNA polymerase II (Pol II) caused major disruptions to enhancer-promoter contacts. Paused Pol II occupancy and the enzymatic activity of poly (ADP-ribose) polymerase 1 (PARP1) stabilized enhancer-promoter contacts. Based on our findings, we propose an updated model that couples transcriptional dynamics and enhancer-promoter communication.

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 July 08, 2022.
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RNA polymerase II and PARP1 shape enhancer-promoter contacts
Gilad Barshad, James J. Lewis, Alexandra G. Chivu, Abderhman Abuhashem, Nils Krietenstein, Edward J. Rice, Oliver J. Rando, Anna-Katerina Hadjantonakis, Charles G. Danko
bioRxiv 2022.07.07.499190; doi: https://doi.org/10.1101/2022.07.07.499190
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RNA polymerase II and PARP1 shape enhancer-promoter contacts
Gilad Barshad, James J. Lewis, Alexandra G. Chivu, Abderhman Abuhashem, Nils Krietenstein, Edward J. Rice, Oliver J. Rando, Anna-Katerina Hadjantonakis, Charles G. Danko
bioRxiv 2022.07.07.499190; doi: https://doi.org/10.1101/2022.07.07.499190

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