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Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement
The immunoglobulin κ light chain intronic enhancer (iE(κ)) activates κ rearrangement and is required to maintain the earlier or more efficient rearrangement of κ versus lambda (λ). To understand the mechanism of how iE(κ) regulates κ rearrangement, we employed homologous recombination to mutate indi...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211861/ https://www.ncbi.nlm.nih.gov/pubmed/15504821 http://dx.doi.org/10.1084/jem.20041135 |
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author | Inlay, Matthew A. Tian, Hua Lin, Tongxiang Xu, Yang |
author_facet | Inlay, Matthew A. Tian, Hua Lin, Tongxiang Xu, Yang |
author_sort | Inlay, Matthew A. |
collection | PubMed |
description | The immunoglobulin κ light chain intronic enhancer (iE(κ)) activates κ rearrangement and is required to maintain the earlier or more efficient rearrangement of κ versus lambda (λ). To understand the mechanism of how iE(κ) regulates κ rearrangement, we employed homologous recombination to mutate individual functional motifs within iE(κ) in the endogenous κ locus, including the NF-κB binding site (κB), as well as κE1, κE2, and κE3 E boxes. Analysis of the impacts of these mutations revealed that κE2 and to a lesser extent κE1, but not κE3, were important for activating κ rearrangement. Surprisingly, mutation of the κB site had no apparent effect on κ rearrangement. Comparable to the deletion of the entire iE(κ), simultaneous mutation of κE1 and κE2 reduces the efficiency of κ rearrangement much more dramatically than either κE1 or κE2 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 κ rearrangement. |
format | Text |
id | pubmed-2211861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22118612008-03-11 Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement Inlay, Matthew A. Tian, Hua Lin, Tongxiang Xu, Yang J Exp Med Brief Definitive Report The immunoglobulin κ light chain intronic enhancer (iE(κ)) activates κ rearrangement and is required to maintain the earlier or more efficient rearrangement of κ versus lambda (λ). To understand the mechanism of how iE(κ) regulates κ rearrangement, we employed homologous recombination to mutate individual functional motifs within iE(κ) in the endogenous κ locus, including the NF-κB binding site (κB), as well as κE1, κE2, and κE3 E boxes. Analysis of the impacts of these mutations revealed that κE2 and to a lesser extent κE1, but not κE3, were important for activating κ rearrangement. Surprisingly, mutation of the κB site had no apparent effect on κ rearrangement. Comparable to the deletion of the entire iE(κ), simultaneous mutation of κE1 and κE2 reduces the efficiency of κ rearrangement much more dramatically than either κE1 or κE2 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 κ rearrangement. The Rockefeller University Press 2004-11-01 /pmc/articles/PMC2211861/ /pubmed/15504821 http://dx.doi.org/10.1084/jem.20041135 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Inlay, Matthew A. Tian, Hua Lin, Tongxiang Xu, Yang Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement |
title | Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement |
title_full | Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement |
title_fullStr | Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement |
title_full_unstemmed | Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement |
title_short | Important Roles for E Protein Binding Sites within the Immunoglobulin κ Chain Intronic Enhancer in Activating V(κ) J(κ) Rearrangement |
title_sort | important roles for e protein binding sites within the immunoglobulin κ chain intronic enhancer in activating v(κ) j(κ) rearrangement |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211861/ https://www.ncbi.nlm.nih.gov/pubmed/15504821 http://dx.doi.org/10.1084/jem.20041135 |
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