ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Deep sequencing of the murine IgH repertoire reveals complex regulation of nonrandom V gene rearrangement frequencies.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 102 citations in OpenAlex.
- An integrated human immunoglobulin germline resource linking allele diversity to expressed repertoire structure.bioRxiv : the preprint server for biology · 2026Article
- Igh nuclear speckle association promotes V(D)J recombination.Nature communications · 2026Article
- Article
- Chromatin folding principles underlying the generation of antibody diversity.Molecular cell · 2026Article
- Germline polymorphisms in the immunoglobulin kappa and lambda loci underpinning antibody light chain repertoire variability.Nature communications · 2025Article
- New insights into antibody structure with implications for specificity, variable region restriction and isotype choice.Nature reviews. Immunology · 2025Review
- CloseRead: a tool for assessing assembly errors in immunoglobulin loci applied to vertebrate long-read genome assemblies.Genome biology · 2025Article
- Exuberant long noncoding RNA expression may sculpt Igh locus topology.Frontiers in immunology · 2025Article
- HTS and scRNA-seq revealed that the location and RSS quality of the mammalian TRBV and TRBJ genes impact biased rearrangement.BMC genomics · 2024Article
- YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity.Genes & development · 2024Article
- Addressing Technical Pitfalls in Pursuit of Molecular Factors That Mediate Immunoglobulin Gene Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Article
- Enhancers within the Ig V Gene Region Orchestrate Chromatin Topology and Regulate V Gene Rearrangement Frequency to Shape the B Cell Receptor Repertoire Specificities.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes.Cell reports · 2023Article
- Multiple lineage-specific epigenetic landscapes at the antigen receptor loci.Aging research (Hong Kong, China) · 2023Article
- Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.Nature communications · 2023Article
- An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation.Nature communications · 2023Article
- Locus architecture and RAG scanning determine antibody diversity.Trends in immunology · 2023Review
- The role of chromatin loop extrusion in antibody diversification.Nature reviews. Immunology · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A diverse Ab repertoire is formed through the rearrangement of V, D, and J segments at the IgH (Igh) loci. The C57BL/6 murine Igh locus has >100 functional VH gene segments that can recombine to a rearranged DJH. Although the nonrandom usage of VH genes is well documented, it is not clear what elements determine recombination frequency. To answer this question, we conducted deep sequencing of 5'-RACE products of the Igh repertoire in pro-B cells, amplified in an unbiased manner. Chromatin immunoprecipitation-sequencing results for several histone modifications and RNA polymerase II binding, RNA-sequencing for sense and antisense noncoding germline transcripts, and proximity to CCCTC-binding factor (CTCF) and Rad21 sites were compared with the usage of individual V genes. Computational analyses assessed the relative importance of these various accessibility elements. These elements divide the Igh locus into four epigenetically and transcriptionally distinct domains, and our computational analyses reveal different regulatory mechanisms for each region. Proximal V genes are relatively devoid of active histone marks and noncoding RNA in general, but having a CTCF site near their recombination signal sequence is critical, suggesting that being positioned near the base of the chromatin loops is important for rearrangement. In contrast, distal V genes have higher levels of histone marks and noncoding RNA, which may compensate for their poorer recombination signal sequences and for being distant from CTCF sites. Thus, the Igh locus has evolved a complex system for the regulation of V(D)J rearrangement that is different for each of the four domains that comprise this locus.
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