ArticleThe Journal of experimental medicine2009
Immunoglobulin switch mu sequence causes RNA polymerase II accumulation and reduces dA hypermutation.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 116 citations in OpenAlex.
- Article
- A dynamic RNA hub facilitates activation-induced cytidine deaminase recruitment to the immunoglobulin heavy-chain locus.Molecular cell · 2026Article
- B cell receptor stimulation inhibits class switch recombination through elevated DNA repair.DNA repair · 2026Article
- Somatic hypermutation patterns are shaped by both motif position and sequence grammar.The EMBO journal · 2026Article
- A dynamic RNA hub facilitates activation induced cytidine deaminase recruitment to the immunoglobulin heavy chain locus.bioRxiv : the preprint server for biology · 2026Article
- DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AID.Nature communications · 2026Article
- RNA 2'-O-methylation promotes persistent R-loop formation and AID-mediated IgH class switch recombination.BMC biology · 2024Article
- 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
- Mechanism and regulation of secondary immunoglobulin diversification.Cell cycle (Georgetown, Tex.) · 2023Review
- Article
- Promoter Proximity Defines Mutation Window for VJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Switch Tandem Repeats Influence the Choice of the Alternative End-Joining Pathway in Immunoglobulin Class Switch Recombination.Frontiers in immunology · 2022Article
- Small Molecule Inhibitors of Activation-Induced Deaminase Decrease Class Switch Recombination in B Cells.ACS pharmacology & translational science · 2021Article
- Long-Range Control of Class Switch Recombination by Transcriptional Regulatory Elements.Frontiers in immunology · 2021Review
- What Targets Somatic Hypermutation to the Immunoglobulin Loci?Viral immunology · 2020Review
- From Influenza Virus Infections to Lupus: Synchronous Estrogen ReceptorViral immunology · 2020Article
- Article
- Current insights into the mechanism of mammalian immunoglobulin class switch recombination.Critical reviews in biochemistry and molecular biology · 2019Review
- Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity.Cellular & molecular immunology · 2018Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Repetitive DNA sequences in the immunoglobulin switch mu region form RNA-containing secondary structures and undergo hypermutation by activation-induced deaminase (AID). To examine how DNA structure affects transcription and hypermutation, we mapped the position of RNA polymerase II molecules and mutations across a 5-kb region spanning the intronic enhancer to the constant mu gene. For RNA polymerase II, the distribution was determined by nuclear run-on and chromatin immunoprecipitation assays in B cells from uracil-DNA glycosylase (UNG)-deficient mice stimulated ex vivo. RNA polymerases were found at a high density in DNA flanking both sides of a 1-kb repetitive sequence that forms the core of the switch region. The pileup of polymerases was similar in unstimulated and stimulated cells from Ung(-/-) and Aid(-/-)Ung(-/-) mice but was absent in cells from mice with a deletion of the switch region. For mutations, DNA was sequenced from Ung(-/-) B cells stimulated in vivo. Surprisingly, mutations of A nucleotides, which are incorporated by DNA polymerase eta, decreased 10-fold before the repetitive sequence, suggesting that the polymerase was less active in this region. We propose that altered DNA structure in the switch region pauses RNA polymerase II and limits access of DNA polymerase eta during hypermutation.
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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.