Modeling G4s in chromatin context confirms partial nucleosome exclusion and reveals nucleosome-disrupting effects of the least selective G4 ligands

G-quadruplexes (G4s) are gaining increasing attention as possible regulators of chromatin packaging, and robust approaches to their studies in pseudo-native context are much needed. Here, we designed a simple in vitro model of G4-prone genomic DNA and employed it to elucidate the impact of G4s and G4-stabilizing ligands on nucleosome occupancy. We obtained two 226-bp dsDNA constructs composed of the strong nucleosome positioning sequence and an internucleosomal DNA-imitating tail. The tail was G4-free in the control construct and harbored a “strong” (stable) G4 motif in the construct of interest. An additional “weak” (semi-stable) G4 motif was found within the canonical nucleosome positioning sequence. Both G4s were confirmed by optical methods and 1H NMR spectroscopy. Electrophoretic mobility assays showed that the weak G4 motif did not obstruct nucleosome assembly, while the strong G4 motif in the tail sequence diminished nucleosome yield. Atomic force microscopy data and molecular modeling confirmed that the strong G4 was maintained in the tail of the correctly assembled nucleosome structure. Using both in vitro and in silico models, we probed three known G4 ligands and detected nucleosome-disrupting effects of the least selective ligand. Our results are in line with the negative correlation between stable G4s and nucleosome density, support G4 tolerance between regularly positioned nucleosomes, and highlight the importance of considering chromatin context when targeting genomic G4s.

Authors
Pavlova Iuliia1, 2 , Barinov Nikolay1 , Novikov Roman3, 4 , Severov Vjacheslav1 , Iudin Mikhail1, 2 , Vedekhina Tatiana1 , Larin Andrey1, 11 , Babenko Vladislav1, 11 , Aralov Andrey5 , Gnuchikh Evgeny6 , Sardushkin Makar7 , Klinov Dmitry 1, 8 , Tsvetkov Vladimir 1, 9, 10 , Varizhuk Anna1, 2, 11
Journal
Biochimie
Publisher
Elsevier B.V.
Language
English
Pages
8-21
Status
Published
Volume
204
Year
2023
Organizations
  • 1 Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, 119435, Russia
  • 2 Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia
  • 3 Engelhardt Institute of Molecular Biology, Moscow, 119991, Russia
  • 4 N.D. Zelinsky Institute of Organic Chemistry, Moscow, 19991, Russia
  • 5 Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, 119435, Russia
  • 6 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia
  • 7 National Research Center Kurchatov Institute, Kurchatov Genomic Center, Moscow, 123182, Russia
  • 8 Mendeleev University of Chemical Technology of Russia, 125047, Moscow, Russia
  • 9 Peoples' Friendship University of Russia (RUDN University), 117198, Moscow, Russia
  • 10 Institute of Biodesign and Complex System Modeling, I.M. Sechenov First Moscow State Medical University, Moscow, 119991, Russia
  • 11 A.V. Topchiev Institute of Petrochemical Synthesis, Leninsky Prospect Str. 29, Moscow, 119991, Russia
Date of creation
02.07.2024
Date of change
02.07.2024
Short link
https://repository.rudn.ru/en/records/article/record/112298/
Share

Other records

ОСОБЕННОСТИ НАСТАВНИЧЕСТВА В КОНТЕКСТЕ СОВРЕМЕННЫХ УСЛОВИЙ ФУНКЦИОНИРОВАНИЯ И РАЗВИТИЯ СИСТЕМЫ ОБРАЗОВАНИЯ

Article
Фомина О.Е., Ростовская Т.К.
Вестник Южно-Российского государственного технического университета (Новочеркасского политехнического института). Серия: Социально-экономические науки. Федеральное государственное бюджетное образовательное учреждение высшего образования Южно-Российский государственный политехнический университет (НПИ) имени М.И. Платова. Vol. 16. 2023. P. 130-143

INTEGRATED GLOBAL ASSESSMENT OF THE NATURAL FOREST CARBON POTENTIAL

Article
Mo Lidong, Zohner C.M., Reich P.B., Liang Jingjing, De Miguel Sergio, Nabuurs Gert-Jan, Renner S.S., Van den Hoogen Johan, Araza Arnan, Herold Martin, Mirzagholi Leila, Ma Haozhi, Averill Colin, Phillips O.L., Gamarra J.G., Hordijk Iris, Routh Devin, Abegg Meinrad, Adou Yao Y.C., Alberti Giorgio, Almeyda Zambrano A.M., Alvarado B.V., Alvarez-Dávila Esteban, Alvarez-Loayza Patricia, Alves L.F., Amaral Iêda, Ammer Christian, Antón-Fernández Clara, Araujo-Murakami Alejandro, Arroyo Luzmila, Avitabile Valerio, Aymard G.A., Baker T.R., Bałazy Radomir, Banki Olaf, Barroso J.G., Bastian M.L., Bastin Jean-Francois, Birigazzi Luca, Birnbaum Philippe, Bitariho Robert, Boeckx Pascal, Bongers Frans, Bouriaud Olivier, Brancalion P.H., Brandl Susanne, Brearley F.Q., Brienen Roel, Broadbent E.N., Bruelheide Helge, Bussotti Filippo, Cazzolla Gatti Roberto, César R.G., Cesljar Goran, Chazdon R.L., Chen H.Y., Chisholm Chelsea, Cho Hyunkook, Cienciala Emil, Clark Connie, Clark David, Colletta G.D., Coomes D.A., Cornejo Valverde Fernando, Corral-Rivas J.J., Crim P.M., Cumming J.R., Dayanandan Selvadurai, De Gasper A.L., Decuyper Mathieu, Derroire Géraldine, DeVries Ben, Djordjevic Ilija, Dolezal Jiri, Dourdain Aurélie, Engone Obiang N.L., Enquist B.J., Eyre T.J., Fandohan A.B., Fayle T.M., Feldpausch T.R., Ferreira L.V., Finér Leena, Fischer Markus, Fletcher Christine, Frizzera Lorenzo, Gianelle Damiano, Glick H.B., Harris D.J., Hector Andrew, Hemp Andreas, Hengeveld Geerten, Hérault Bruno, Herbohn J.L., Hillers Annika, Honorio Coronado E.N., Hui Cang, Ibanez Thomas, Imai Nobuo, Jagodziński A.M., Jaroszewicz Bogdan, Johannsen V.K., Joly C.A., Jucker Tommaso, Jung Ilbin, Karminov Viktor, Kartawinata Kuswata, Kearsley Elizabeth, Kenfack David, Kennard D.K., Kepfer-Rojas Sebastian, Keppel Gunnar, Khan M.L., Killeen T.J., Kim H.S., Kitayama Kanehiro, Köhl Michael, Korjus Henn, Kraxner Florian, Kucher Dmitry, Laarmann Diana, Lang Mait, Lu Huicui, Lukina N.V., Maitner B.S., Malhi Yadvinder, Marcon Eric, Marimon B.S., Marimon-Junior B.H., Marshall A.R., Martin E.H., Meave J.A., Melo-Cruz Omar, Mendoza Casimiro, Mendoza-Polo Irina, Miscicki Stanislaw, Merow Cory, Monteagudo Mendoza Abel, Moreno V.S., Mukul S.A., Mundhenk Philip, Nava-Miranda M.G., Neill David, Neldner V.J., Nevenic R.V., Ngugi M.R., Niklaus P.A., Oleksyn Jacek, Ontikov Petr, Ortiz-Malavasi Edgar, Pan Yude, Paquette Alain, Parada-Gutierrez Alexander, Parfenova E.I., Park Minjee, Parren Marc, Parthasarathy Narayanaswamy, Peri P.L., Pfautsch Sebastian, Picard Nicolas, Piedade M.T., Piotto Daniel, Pitman N.C., Poulsen A.D., Poulsen J.R., Pretzsch Hans, Ramirez Arevalo Freddy, Restrepo-Correa Zorayda, Rodeghiero Mirco, Rolim S.G., Roopsind Anand, Rovero Francesco, Rutishauser Ervan, Saikia Purabi, Salas-Eljatib Christian, Saner Philippe, Schall Peter, Schelhaas Mart-Jan, Schepaschenko Dmitry, Scherer-Lorenzen Michael, Schmid Bernhard, Schöngart Jochen, Searle E.B., Seben Vladimír, Serra-Diaz J.M., Sheil Douglas, Shvidenko A.Z., Silva-Espejo J.E., Silveira Marcos, Singh James, Sist Plinio, Slik Ferry, Sonké Bonaventure, Souza A.F., Stereńczak K.J., Svenning Jens-Christian, Svoboda Miroslav, Swanepoel Ben, Targhetta Natalia, Tchebakova Nadja, Ter Steege Hans, Thomas Raquel, Tikhonova Elena, Umunay P.M., Usoltsev V.A., Valencia Renato, Valladares Fernando, Van der Plas Fons, Van Do Tran, Van Nuland M.E., Vasquez R.M., Verbeeck Hans, Viana Helder, Vibrans A.C., Vieira Simone, Von Gadow Klaus, Wang Hua-Feng, Watson J.V., Werner G.D., Wiser S.K., Wittmann Florian, Woell Hannsjoerg, Wortel Verginia, Zagt Roderik, Zawiła-Niedźwiecki Tomasz, Zhang Chunyu, Zhao Xiuhai, Zhou Mo, Zhu Zhi-Xin, Zo-Bi I.C., Gann G.D., Crowther T.W.
NATURE. Springer Nature. Vol. 624. 2023. P. 92-101