ArticlePLoS genetics2021
IgH 3' regulatory region increases ectopic class switch recombination.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Core enhancers of the 3'RR optimize IgH nuclear position and loop conformation for successful oriented class switch recombination.Nucleic acids research · 2024Article
- Differential analysis of immunoglobulin gene expression pattern in chickens of distinct breeds and developmental periods.Journal of animal science · 2024Article
- Mechanism and regulation of secondary immunoglobulin diversification.Cell cycle (Georgetown, Tex.) · 2023Review
- Distinct B-Cell Specific Transcriptional Contexts of the BCL2 Oncogene Impact Pre-Malignant Development in Mouse Models.Cancers · 2022Article
- DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022Review
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA lesions inflicted by activation-induced deaminase (AID) instrumentally initiate the processes reshaping immunoglobulin genes in mature B-cells, from local somatic hypermutation (SHM) to junctions of distant breaks during class switch recombination (CSR). It remains incompletely understood how these divergent outcomes of AID attacks are differentially and temporally focused, with CSR strictly occurring in the Ig heavy chain (IgH) locus while SHM concentrates on rearranged V(D)J regions in the IgH and Ig light chain loci. In the IgH locus, disruption of either the 3'Regulatory Region (3'RR) super-enhancer or of switch (S) regions preceding constant genes, profoundly affects CSR. Reciprocally, we now examined if these elements are sufficient to induce CSR in a synthetic locus based on the Igκ locus backbone. Addition of a surrogate "core 3'RR" (c3'RR) and of a pair of transcribed and spliced Switch regions, together with a reporter system for "κ-CSR" yielded a switchable Igκ locus. While the c3'RR stimulated SHM at S regions, it also lowered the local SHM threshold necessary for switch recombination to occur. The 3'RR thus both helps recruit AID to initiate DNA lesions, but then also promotes their resolution through long-distance synapses and recombination following double-strand breaks.
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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.