Epigenetic aspects of lymphocyte antigen receptor gene rearrangement or 'when stochasticity completes randomness'

Autor: Sébastien Jaeger, Pierre Ferrier, Bastien Fernandez
Přispěvatelé: Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CPT - Ex E8 Dynamique non linéaire, Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Inserm and CNRS. Grant Number: PIOF-GA-2009-235741, CNRS in the framework of the project PEPS Theoretical, Physics and Interfaces. Grant Number: PIOF-GA-2009-235741, Commission of the European Communities, Agence Nationale de la Recherche, Institut National du Cancer, Association pour la Recherche sur le Cancer, Fondation pour la Recherche Médicale, Fondation Princesse Grace de la Principauté de Monaco, Marie Curie EU fellowship. Grant Number: PIOF-GA-2009-235741, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Rok vydání: 2012
Předmět:
MESH: T-Lymphocytes/metabolism
T-Lymphocytes
Immunology
Receptors
Antigen
T-Cell
MESH: Receptors
Antigen
T-Cell/immunology
MESH: Gene Rearrangement
T-Lymphocyte/genetics
Biology
MESH: Gene Rearrangement
T-Lymphocyte/immunology
Gene Rearrangement
T-Lymphocyte
MESH: Models
Immunological
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Recombination-activating gene
Epigenesis
Genetic
03 medical and health sciences
0302 clinical medicine
MESH: T-Lymphocytes/immunology
allelic exclusion
Recombinase
Immunology and Allergy
Animals
Humans
T-cell receptor
MESH: Animals
Epigenetics
MESH: Models
Genetic
Review Articles
030304 developmental biology
Genetics
0303 health sciences
Stochastic Processes
MESH: Humans
epigenetics
MESH: Receptors
Antigen
T-Cell/genetics
Models
Genetic
V(D)J recombination
Models
Immunological
Gene rearrangement
MESH: V(D)J Recombination/genetics
Acquired immune system
V(D)J Recombination
Allelic exclusion
MESH: V(D)J Recombination/immunology
MESH: Stochastic Processes
chromatin
MESH: Epigenesis
Genetic/genetics
MESH: Epigenesis
Genetic/immunology
immunoglobulin
030215 immunology
Zdroj: Immunology
Immunology, 2013, 139 (2), pp.141-150. ⟨10.1111/imm.12057⟩
Immunology, Wiley, 2013, 139 (2), pp.141-150. ⟨10.1111/imm.12057⟩
ISSN: 1365-2567
0019-2805
DOI: 10.1111/imm.12057⟩
Popis: International audience; To perform their specific functional role, B and T lymphocytes, cells of the adaptive immune system of jawed vertebrates, need to express one (and, preferably, only one) form of antigen receptor, i.e. the immunoglobulin or T-cell receptor (TCR), respectively. This end goal depends initially on a series of DNA cis-rearrangement events between randomly chosen units from separate clusters of V, D (at some immunoglobulin and TCR loci) and J gene segments, a biomolecular process collectively referred to as V(D)J recombination. V(D)J recombination takes place in immature T and B cells and relies on the so-called RAG nuclease, a site-specific DNA cleavage apparatus that corresponds to the lymphoid-specific moiety of the VDJ recombinase. At the genome level, this recombinase's mission presents substantial biochemical challenges. These relate to the huge distance between (some of) the gene segments that it eventually rearranges and the need to achieve cell-lineage-restricted and developmentally ordered routines with at times, mono-allelic versus bi-allelic discrimination. The entire process must be completed without any recombination errors, instigators of chromosome instability, translocation and, potentially, tumorigenesis. As expected, such a precisely choreographed and yet potentially risky process demands sophisticated controls; epigenetics demonstrates what is possible when calling upon its many facets. In this vignette, we will recall the evidence that almost from the start appeared to link the two topics, V(D)J recombination and epigenetics, before reviewing the latest advances in our knowledge of this joint venture.
Databáze: OpenAIRE
Externí odkaz: