The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 25 October 2004 doi:10.1084/jem.20041135
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 9, 1205-1211
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1916K)
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 Inlay, M. A.
Right arrow Articles by Xu, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Inlay, M. A.
Right arrow Articles by Xu, Y.
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?

Brief Definitive Report

 Important Roles for E Protein Binding Sites within the Immunoglobulin {kappa} Chain Intronic Enhancer in Activating V{kappa} J{kappa} Rearrangement

Matthew A. Inlay, Hua Tian, Tongxiang Lin, and Yang Xu

Division of Biological Sciences, University of California, San Diego, CA 92093

Address correspondence to Yang Xu, Div. of Biological Sciences, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0322. Phone: (858) 822-1084; Fax: (858) 534-0053; email: yangxu{at}ucsd.edu

The immunoglobulin {kappa} light chain intronic enhancer (iE{kappa}) activates {kappa} rearrangement and is required to maintain the earlier or more efficient rearrangement of {kappa} versus lambda ({lambda}). To understand the mechanism of how iE{kappa} regulates {kappa} rearrangement, we employed homologous recombination to mutate individual functional motifs within iE{kappa} in the endogenous {kappa} locus, including the NF-{kappa}B binding site ({kappa}B), as well as {kappa}E1, {kappa}E2, and {kappa}E3 E boxes. Analysis of the impacts of these mutations revealed that {kappa}E2 and to a lesser extent {kappa}E1, but not {kappa}E3, were important for activating {kappa} rearrangement. Surprisingly, mutation of the {kappa}B site had no apparent effect on {kappa} rearrangement. Comparable to the deletion of the entire iE{kappa}, simultaneous mutation of {kappa}E1 and {kappa}E2 reduces the efficiency of {kappa} rearrangement much more dramatically than either {kappa}E1 or {kappa}E2 mutation alone. Because E2A family proteins are the only known factors that bind to these E boxes, these findings provide unambiguous evidence that E2A is a key regulator of {kappa} rearrangement.

Key Words: B cell development • V(D)J recombination • accessibility • monospecificity • transcription factor


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