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

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  • معلومة اضافية
    • Contributors:
      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]; 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 )
    • الموضوع:
      2017
    • نبذة مختصرة :
      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.
    • ISSN:
      1949-2553
    • الرقم المعرف:
      10.18632/oncotarget.16941⟩
    • Rights:
      OPEN
    • الرقم المعرف:
      edsair.pmid.dedup....ff4d4e9a930ea994462ca80ba9d07097