Document Detail


Epigenetic aspects of lymphocyte antigen receptor gene rearrangement or 'when stochasticity completes randomness'.
MedLine Citation:
PMID:  23278765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sébastien Jaeger; Bastien Fernandez; Pierre Ferrier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-07-01     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  141-50     Citation Subset:  IM    
Copyright Information:
© 2012 Inserm Immunology © 2012 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Epigenesis, Genetic / genetics,  immunology*
Gene Rearrangement, T-Lymphocyte / genetics,  immunology*
Humans
Models, Genetic
Models, Immunological
Receptors, Antigen, T-Cell / genetics,  immunology*
Stochastic Processes
T-Lymphocytes / immunology,  metabolism
V(D)J Recombination / genetics,  immunology*
Chemical
Reg. No./Substance:
0/Receptors, Antigen, T-Cell
Comments/Corrections

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