Assessing the role of the T cell receptor beta gene enhancer in regulating coding joint formation during V(D)J recombination
Autor: | Olivier Cabaud, Christophe Verthuy, Sophie Gorbatch, Salvatore Spicuglia, Pierre Ferrier, Noëlle Mathieu, Corinne Fernex, William M. Hempel, Anne-Odile Hueber |
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Přispěvatelé: | Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2003 |
Předmět: |
DNA Repair
MESH: Flow Cytometry Biochemistry Polymerase Chain Reaction MESH: Mice Knockout Mice 0302 clinical medicine MESH: Animals MESH: Models Genetic VDJ Recombinases Mice Knockout Recombination Genetic MESH: DNA Repair 0303 health sciences MESH: VDJ Recombinases MESH: DNA Nucleotidyltransferases MESH: Enhancer Elements (Genetics) V(D)J recombination Flow Cytometry Chromatin Allelic exclusion Enhancer Elements Genetic DNA Nucleotidyltransferases Genes T-Cell Receptor beta MESH: Recombination Genetic DNA repair MESH: Mice Transgenic MESH: Genes T-Cell Receptor beta Locus (genetics) Mice Transgenic chemical and pharmacologic phenomena [SDV.CAN]Life Sciences [q-bio]/Cancer Thymus Gland Biology MESH: Chromatin 03 medical and health sciences MESH: Mice Inbred C57BL Animals Enhancer Molecular Biology Gene MESH: Mice Alleles 030304 developmental biology Models Genetic MESH: Alleles T-cell receptor MESH: Polymerase Chain Reaction [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology MESH: Thymus Gland Molecular biology Mice Inbred C57BL 030215 immunology |
Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2003, 278 (20), pp.18101-9. ⟨10.1074/jbc.M212647200⟩ Journal of Biological Chemistry, 2003, 278 (20), pp.18101-9. ⟨10.1074/jbc.M212647200⟩ |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M212647200⟩ |
Popis: | International audience; To assess the role of the T cell receptor (TCR) beta gene enhancer (Ebeta) in regulating the processing of VDJ recombinase-generated coding ends, we assayed TCRbeta rearrangement of Ebeta-deleted (DeltaEbeta) thymocytes in which cell death is inhibited via expression of a Bcl-2 transgene. Compared with DeltaEbeta, DeltaEbeta Bcl-2 thymocytes show a small accumulation of TCRbeta standard recombination products, including coding ends, that involves the proximal Dbeta-Jbeta and Vbeta14 loci but not the distal 5' Vbeta genes. These effects are detectable in double negative pro-T cells, predominate in double positive pre-T cells, and correlate with regional changes in chromosomal structure during double negative-to-double positive differentiation. We propose that Ebeta, by driving long range nucleoprotein interactions and the control of locus expression and chromatin structure, indirectly contributes to the stabilization of coding ends within the recombination processing complexes. The results also illustrate Ebeta-dependent and -independent changes in chromosomal structure, suggesting distinct modes of regulation of TCRbeta allelic exclusion depending on the position within the locus. |
Databáze: | OpenAIRE |
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