The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 295K)
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 Roberts, J. L.
Right arrow Articles by Krangel, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roberts, J. L.
Right arrow Articles by Krangel, M. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1997/1/131/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 1, January 6, 1997 131-140

Articles

Developmental Regulation of VDJ Recombination By the Core Fragment of the T Cell Receptor {alpha} Enhancer

Joseph L. Roberts, Pilar Lauzurica, and Michael S. Krangel

From the Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710

The role of T cell receptor {alpha} enhancer (E{alpha}) cis-acting elements in the developmental regulation of VDJ recombination at the TCR {alpha}/{delta} locus was examined in transgenic mice containing variants of a minilocus VDJ recombination substrate. We demonstrate that the 116-bp T{alpha}1,2 core enhancer fragment of the 1.4-kb E{alpha} is sufficient to activate the enhancer-dependent step of minilocus rearrangement, and that within T{alpha}1,2, intact binding sites for TCF/LEF and Ets family transcription factors are essential. Although minilocus rearrangement under the control of the 1.4-kb E{alpha} initiates at fetal day 16.5 and is strictly limited to {alpha}β T cells, we find that rearrangement under the control of T{alpha}1,2 initiates slightly earlier during ontogeny and occurs in both {gamma}{delta} and {alpha}β T cells. We conclude that the core fragment of E{alpha} can establish accessibility to the recombinase in developing thymocytes in vivo in a fashion that is dependent on the binding of TCF/LEF and Ets family transcription factors, but that these and other factors that bind to the E{alpha} core cannot account for the precise developmental onset of accessibility that is provided by the intact E{alpha}. Rather, our data suggests a critical role for factors that bind E{alpha} outside of the core T{alpha}1,2 region in establishing the precise developmental onset of TCR {alpha} rearrangement in vivo.

Address correspondence to Michael S. Krangel, Department of Immunology, PO Box 3010, Duke University Medical Center, Durham, NC 27710. The current address of P. Lauzurica is Seccion de Immunologia, Hospital de la Princesa, 28006 Madrid, Spain.

This work was supported by National Institutes of Health grant GM41052. M.S. Krangel is the recipient of American Cancer Society Faculty Research Award FRA-414. J.L. Roberts was supported in part by Public Health Service Training grant CA09058.

1Abbreviations used in this paper: DN, double negative; DP, double positive; E{alpha}, {alpha} enhancer; E{delta}, {delta} enhancer; HMG, high mobility group; ISP, immature single positive.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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