The Journal of Experimental Medicine
Rockland Immunochemicals for Research
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 467K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Durum, S. K.
Right arrow Articles by Muegge, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Durum, S. K.
Right arrow Articles by Muegge, K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J. Exp. Med., Volume 188, Number 12, December 21, 1998 2233-2241

Interleukin 7 Receptor Control of  T Cell Receptor gamma  Gene Rearrangement: Role of Receptor-associated Chains and Locus Accessibility

By Scott K. Durum,* Serge Candèias,Dagger Hiroshi Nakajima,§ Warren J. Leonard,§ Allison M. Baird,parallel Leslie J. Berg,parallel and Kathrin MueggeDagger

From the * Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland 21702; the Dagger  Intramural Research Support Program, Science Applications International Corp. Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201; the § Laboratory of Molecular Immunology, National Heart Lung and Blood Institute, Bethesda, Maryland 20892; and the parallel  Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605

VDJ recombination of T cell receptor and immunoglobulin loci occurs in immature lymphoid cells. Although the molecular mechanisms of DNA cleavage and ligation have become more clear, it is not understood what controls which target loci undergo rearrangement. In interleukin 7 receptor (IL-7R)alpha -/- murine thymocytes, it has been shown that rearrangement of the T cell receptor (TCR)-gamma locus is virtually abrogated, whereas other rearranging loci are less severely affected. By examining different strains of mice with targeted mutations, we now observe that the signaling pathway leading from IL-7Ralpha to rearrangement of the TCR-gamma locus requires the gamma c receptor chain and the gamma c-associated Janus kinase Jak3. Production of sterile transcripts from the TCR-gamma locus, a process that generally precedes rearrangement of a locus, was greatly repressed in IL-7Ralpha -/- thymocytes. The repressed transcription was not due to a lack in transcription factors since the three transcription factors known to regulate this locus were readily detected in IL-7Ralpha -/- thymocytes. Instead, the TCR-gamma locus was shown to be methylated in IL-7Ralpha -/- thymocytes. Treatment of IL-7Ralpha -/- precursor T cells with the specific histone deacetylase inhibitor trichostatin A released the block of TCR-gamma gene rearrangement. This data supports the model that IL-7R promotes TCR-gamma gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus.

Key words: T cell receptor;  thymus;  VDJ recombination;  interleukin 7;  T cell receptor gamma  locus;  gamma /delta T cells


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS