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PubMed Central
Article . 2006
Data sources: PubMed Central
The Journal of Experimental Medicine
Article . 2006 . Peer-reviewed
Data sources: Crossref
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Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences

Authors: Yang, Shu Yuan; Fugmann, Sebastian D.; Schatz, David G.;

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

Abstract

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.

Related Organizations
Keywords

B-Lymphocytes, Transcription, Genetic, Gene Conversion, Gene Expression, Receptors, Antigen, B-Cell, Articles, Transfection, Actins, Enhancer Elements, Genetic, Peptide Elongation Factor 1, Immunoglobulin M, Bacteriophage T7, Cell Line, Tumor, Cytidine Deaminase, Mutation, Animals, Genes, Immunoglobulin Light Chain, Somatic Hypermutation, Immunoglobulin, Immunoglobulin Heavy Chains, Promoter Regions, Genetic, Gene Deletion

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
49
Average
Top 10%
Top 10%
Green
bronze