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3. Dimeric G-quadruplex motifs determine a large fraction of strong replication origins in vertebrates

Author

Poulet-Benedetti, Jérémy, Tonnerre-Doncarli, Caroline, Valton, Anne-Laure, Laurent, Marc, Gérard, Marie, Barinova, Natalja, Parisis, Nikolaos, Massip, Florian, Picard, Franck, Prioleau, Marie-Noëlle, Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Howard Hughes Medical Institute (HHMI), École des Mines de Paris, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), massip, florian, and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience; Abstract Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce assembly of an efficient minimal replication origin without inducing transcription, and that dimeric pG4s in replication origins are located in an NFR next to well-positioned nucleosomes enriched in H2A.Z. Thus, our data suggest a crucial role for dimeric pG4s in the organization and duplication of vertebrate genomes.

Published
2022
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5. The IGH locus relocalizes to a 'recombination compartment' in the perinucleolar region of differentiating B-lymphocytes

Author

Pichugin, Andrey, Iarovaia, Olga V., Gavrilov, Alexey, Sklyar, Ilya, Barinova, Natalja, Barinov, Aleksandr, Ivashkin, Evgeny, Caron, Gersende, Aoufouchi, Said, Razin, Sergey V., Fest, Thierry, Lipinski, Marc, Vassetzky, Yegor S., Peter the Great St. Petersburg Polytechnic University (SPbPU), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institute of Gene Biology, Russian Academy of Sciences, Pôle biologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Réparation de l’ADN (CNRS UMR 8200), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Faculty of biology, Lomonosov Moscow State University (MSU), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Hôpital Pontchaillou, This research was supported by the Russian Science Foundation, project #14-24-00022 to SVR and project #14-15-00199 to YSV, by Russian Foundation for Basic Research, project #16-54-16014 to SVR, and by grants from INSERM (ENVIBURKITT) and La Ligue Contre le Cancer (M27231) to YSV., Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
B-Lymphocytes, Microscopy, Confocal, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Differentiation, differentiation, Germinal Center, Lymphocyte Activation, Chromosome Section, Immunoglobulin Class Switching, recombination, Research Paper: Chromosome, Cell Line, Tumor, Cytidine Deaminase, immunoglobulin genes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, chromatin, Somatic Hypermutation, Immunoglobulin, Immunoglobulin Heavy Chains, Cell Nucleolus, Cells, Cultured, In Situ Hybridization, Fluorescence
Abstract

International audience; The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci. Our observations are consistent with the proposal that these IGH gene rearrangements take place in a specific perinucleolar "recombination compartment" where AID could be sequestered thus limiting the extent of its potentially deleterious off-target effects.

Published
2017
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6. TheIGHlocus relocalizes to a “recombination compartment” in the perinucleolar region of differentiating B-lymphocytes

Author

Pichugin, Andrey, primary, Iarovaia, Olga V., additional, Gavrilov, Alexey, additional, Sklyar, Ilya, additional, Barinova, Natalja, additional, Barinov, Aleksandr, additional, Ivashkin, Evgeny, additional, Caron, Gersende, additional, Aoufouchi, Said, additional, Razin, Sergey V., additional, Fest, Thierry, additional, Lipinski, Marc, additional, and Vassetzky, Yegor S., additional

Published
2017
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