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Original Article

Noëlle Mathieu^a, William M. Hempel^a, Salvatore Spicuglia^a, Christophe Verthuy^a, and Pierre Ferrier^a

^a Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale–Centre National de la Recherche Scientifique (INSERM-CNRS) de Marseille-Luminy, 13288 Marseille, France
CIML, Case 906, 13288 Marseille Cedex 9, France.33-491-26943033-491-269435

ferrier{at}ciml.univ-mrs.fr

Gene targeting studies have shown that T cell receptor (TCR)-β gene expression and recombination are inhibited after deletion of an enhancer (Eβ) located at the 3' end of the 500-kb TCR-β locus. Using knockout mouse models, we have measured, at different regions throughout the TCR-β locus, the effects of Eβ deletion on molecular parameters believed to reflect epigenetic changes associated with the control of gene activation, including restriction endonuclease access to chromosomal DNA, germline transcription, DNA methylation, and histone H3 acetylation. Our results demonstrate that, in early developing thymocytes, Eβ contributes to major chromatin remodeling directed to an 25-kb upstream domain comprised of the Dβ-Jβ locus regions. Accordingly, treatment of Eβ-deleted thymocytes with the histone deacetylase inhibitor trichostatin A relieved the block in TCR-β gene expression and promoted recombination within the Dβ-Jβ loci. Unexpectedly, however, epigenetic processes at distal Vβ genes on the 5' side of the locus and at the 3' proximal Vβ14 gene appear to be less dependent on Eβ, suggesting that Eβ activity is confined to a discrete region of the TCR-β locus. These findings have implications with respect to the developmental control of TCR-β gene recombination, and the process of allelic exclusion at this locus.

Key Words: T cell receptor • thymus • lymphocyte differentiation • chromatin • T cell receptor rearrangement

Abbreviations used in this paper: CHIP, chromatin immunoprecipitation; DN, double negative; DP, double positive; DSB, double strand break; Eβ, TCR-β gene enhancer; GT, germline transcript; LM, ligation-mediated; RAG, recombination activating gene; RgT, rearranged transcript; RSS, recombination signal sequence(s); RT, reverse transcription; TSA, trichostatin A; wt, wild-type.

© 2000 The Rockefeller University Press

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This article has been cited by other articles:

• Krangel, M. S. (2001). V(D)j Recombination Becomes Accessible. JEM 193: f27-f30 [Full Text]  

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