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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...

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Autores principales: Inlay, Matthew A., Tian, Hua, Lin, Tongxiang, Xu, Yang
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
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.
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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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