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G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing

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Title: G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing
Authors: Esnault, Cyril, Garcia-Oliver, Encar, El Aabidine, Amal, Zine, Robert, Marie-Cécile, Magat, Talha, Gawron, Kevin, Basyuk, Eugénia, Karpinska, Magda, Pigeot, Alexia, Cucchiarini, Anne, Luo, Yu, Verga, Daniele, Mourad, Raphael, Radulescu, Ovidiu, Mergny, Jean-Louis, Bertrand, Edouard, Andrau, Jean-Christophe
Contributors: Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de génétique humaine (IGH), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X), Institut Polytechnique de Paris (IP Paris)-Institut Polytechnique de Paris (IP Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Pathogen Host Interactions Montpellier (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ANR-18-CE12-0019,Epromoters,Contrôle de la réponse au stress par une nouvelle classe de promoteurs à activité enhancer(2018)
Source: https://hal.science/hal-04286714 ; 2023.
Publisher Information: CCSD
Publication Year: 2023
Collection: Inserm: HAL (Institut national de la santé et de la recherche médicale)
Subject Terms: [SDV]Life Sciences [q-bio]
Description: Despite their central role in transcription, it has been difficult to define universal sequences associated to eukaryotic promoters. Within chromatin context, recruitment of the transcriptional machinery requires opening of the promoter but how DNA elements could contribute to this process has remained elusive. Here, we show that G-quadruplex (G4) secondary structures are highly enriched mammalian core promoter elements. G4s are located at the deepest point of nucleosome exclusion at promoters and correlate with maximum promoter activity. We found that experimental G4s exclude nucleosomes both in vivo and in vitro and display a strong positioning potential. At model promoters, impairing G4s affected both transcriptional activity and chromatin opening. G4 destabilization also resulted in an inactive promoter state and affected transition to effective RNA production in live imaging experiments. Finally, G4 stabilization resulted in global reduction of proximal promoter pausing. Altogether, our data introduce G4s as bona fide promoter elements allowing nucleosome exclusion and facilitating pause release by the RNA Polymerase II.
Document Type: report
Language: English
Relation: BIORXIV: 2023.02.24.529838
DOI: 10.1101/2023.02.24.529838
Availability: https://hal.science/hal-04286714
https://hal.science/hal-04286714v1/document
https://hal.science/hal-04286714v1/file/15_Esnault_et_al_BioRxiv_2023.pdf
https://doi.org/10.1101/2023.02.24.529838
Rights: https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.DAACB8C4
Database: BASE
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  Data: G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing
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  Data: Despite their central role in transcription, it has been difficult to define universal sequences associated to eukaryotic promoters. Within chromatin context, recruitment of the transcriptional machinery requires opening of the promoter but how DNA elements could contribute to this process has remained elusive. Here, we show that G-quadruplex (G4) secondary structures are highly enriched mammalian core promoter elements. G4s are located at the deepest point of nucleosome exclusion at promoters and correlate with maximum promoter activity. We found that experimental G4s exclude nucleosomes both in vivo and in vitro and display a strong positioning potential. At model promoters, impairing G4s affected both transcriptional activity and chromatin opening. G4 destabilization also resulted in an inactive promoter state and affected transition to effective RNA production in live imaging experiments. Finally, G4 stabilization resulted in global reduction of proximal promoter pausing. Altogether, our data introduce G4s as bona fide promoter elements allowing nucleosome exclusion and facilitating pause release by the RNA Polymerase II.
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