ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Identification of core DNA elements that target somatic hypermutation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Interpretable deep learning reveals the role of an E-box motif in suppressing somatic hypermutation of AGCT motifs within human immunoglobulin variable regions.Frontiers in immunology · 2024Article
- The IgHFrontiers in immunology · 2023Article
- AID function in somatic hypermutation and class switch recombination.Acta biochimica et biophysica Sinica · 2022Review
- Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- TET3 dioxygenase modulates gene conversion at the avian immunoglobulin variable region via demethylation of non-CpG sites in pseudogene templates.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting.European journal of immunology · 2020Article
- Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells.PloS one · 2016Article
- Topoisomerase I deficiency causes RNA polymerase II accumulation and increases AID abundance in immunoglobulin variable genes.DNA repair · 2015Article
- Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination.Microbiology spectrum · 2015Review
- AID-initiated DNA lesions are differentially processed in distinct B cell populations.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- A source of the single-stranded DNA substrate for activation-induced deaminase during somatic hypermutation.Nature communications · 2014Article
- Generation and repair of AID-initiated DNA lesions in B lymphocytes.Frontiers of medicine · 2014Review
- Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences.PLoS biology · 2014Article
- A critical context-dependent role for E boxes in the targeting of somatic hypermutation.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- The IgH 3' regulatory region controls somatic hypermutation in germinal center B cells.The Journal of experimental medicine · 2013Article
- Multiple transcription factor binding sites predict AID targeting in non-Ig genes.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Somatic hypermutation (SHM) diversifies the V region of Ig genes and underlies the process of affinity maturation, in which B lymphocytes producing high-affinity Abs are generated and selected. SHM is triggered in activated B cells by deamination of deoxycytosine residues mediated by activation-induced deaminase (AID). Whereas mistargeting of SHM and AID results in mutations and DNA damage in many non-Ig genes, they act preferentially at Ig loci. The mechanisms responsible for preferential targeting of SHM and AID activity to Ig loci are poorly understood. Using an assay involving an SHM reporter cassette inserted into the Ig L chain locus (IgL) of chicken DT40 B cells, we have identified a 1.9-kb DIVAC (diversification activator) element derived from chicken IgL that supports high levels of AID-dependent mutation activity. Systematic deletion analysis reveals that targeting activity is spread throughout much of the sequence and identifies two core regions that are particularly critical for function: a 200-bp region within the IgL enhancer, and a 350-bp 3' element. Chromatin immunoprecipitation experiments demonstrate that whereas DIVAC does not alter levels of several epigenetic marks in the mutation cassette, it does increase levels of serine-5 phosphorylated RNA polymerase II in the mutation target region, consistent with an effect on transcriptional elongation/pausing. We propose that multiple, dispersed DNA elements collaborate to recruit and activate the mutational machinery at Ig gene variable regions during SHM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.