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Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences

It is thought that gene conversion (GCV) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes occur in two steps: the generation of uracils in DNA by activation-induced cytidine deaminase, followed by their subsequent repair by various DNA repair pathways to generate sequence-diversified pro...

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Detalles Bibliográficos
Autores principales: Yang, Shu Yuan, Fugmann, Sebastian D., Schatz, David G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118177/
https://www.ncbi.nlm.nih.gov/pubmed/17178919
http://dx.doi.org/10.1084/jem.20061835
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author Yang, Shu Yuan
Fugmann, Sebastian D.
Schatz, David G.
author_facet Yang, Shu Yuan
Fugmann, Sebastian D.
Schatz, David G.
author_sort Yang, Shu Yuan
collection PubMed
description It is thought that gene conversion (GCV) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes occur in two steps: the generation of uracils in DNA by activation-induced cytidine deaminase, followed by their subsequent repair by various DNA repair pathways to generate sequence-diversified products. It is not known how either of the two steps is targeted specifically to Ig loci. Because of the tight link between transcription and SHM, we have investigated the role of endogenous Ig light chain (IgL) transcriptional control elements in GCV/SHM in the chicken B cell line DT40. Promoter substitution experiments led to identification of a strong RNA polymerase II promoter incapable of supporting efficient GCV/SHM. This surprising finding indicates that high levels of transcription are not sufficient for robust GCV/SHM in Ig loci. Deletion of the IgL enhancer in a context in which high-level transcription was not compromised showed that the enhancer is not necessary for GCV/SHM. Our results indicate that cis-acting elements are important for Ig gene diversification, and we propose that targeting specificity is achieved through the combined action of several Ig locus elements that include the promoter.
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spelling pubmed-21181772007-12-13 Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences Yang, Shu Yuan Fugmann, Sebastian D. Schatz, David G. J Exp Med Articles It is thought that gene conversion (GCV) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes occur in two steps: the generation of uracils in DNA by activation-induced cytidine deaminase, followed by their subsequent repair by various DNA repair pathways to generate sequence-diversified products. It is not known how either of the two steps is targeted specifically to Ig loci. Because of the tight link between transcription and SHM, we have investigated the role of endogenous Ig light chain (IgL) transcriptional control elements in GCV/SHM in the chicken B cell line DT40. Promoter substitution experiments led to identification of a strong RNA polymerase II promoter incapable of supporting efficient GCV/SHM. This surprising finding indicates that high levels of transcription are not sufficient for robust GCV/SHM in Ig loci. Deletion of the IgL enhancer in a context in which high-level transcription was not compromised showed that the enhancer is not necessary for GCV/SHM. Our results indicate that cis-acting elements are important for Ig gene diversification, and we propose that targeting specificity is achieved through the combined action of several Ig locus elements that include the promoter. The Rockefeller University Press 2006-12-25 /pmc/articles/PMC2118177/ /pubmed/17178919 http://dx.doi.org/10.1084/jem.20061835 Text en Copyright © 2006, 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 Articles
Yang, Shu Yuan
Fugmann, Sebastian D.
Schatz, David G.
Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
title Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
title_full Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
title_fullStr Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
title_full_unstemmed Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
title_short Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
title_sort control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118177/
https://www.ncbi.nlm.nih.gov/pubmed/17178919
http://dx.doi.org/10.1084/jem.20061835
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