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
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