ArticleProceedings of the National Academy of Sciences of the United States of America2015
CTCF-binding elements 1 and 2 in the Igh intergenic control region cooperatively regulate V(D)J recombination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 63 citations in OpenAlex.
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- A hierarchy of spatial confinements governs chromatin dynamics and genomic encounters.bioRxiv : the preprint server for biology · 2026Article
- Context-dependent regulation of IgH V(D)J recombination by cohesin-STAG1 and cohesin-STAG2.Nature communications · 2026Article
- The insulator EACBE regulates V(D)J recombination of Tcrd gene by modulating chromatin organization.Frontiers in immunology · 2025Article
- Addressing Technical Pitfalls in Pursuit of Molecular Factors That Mediate Immunoglobulin Gene Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Lineage- and stage-specific activity of antigen receptor gene enhancers during lymphocyte development.Frontiers in epigenetics and epigenomics · 2024Review
- Genome control by SMC complexes.Nature reviews. Molecular cell biology · 2023Review
- Contribution of the IGCR1 regulatory element and the 3'Proceedings of the National Academy of Sciences of the United States of America · 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
- The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.The Journal of experimental medicine · 2021Article
- Repair of programmed DNA lesions in antibody class switch recombination: common and unique features.Genome instability & disease · 2021Review
- Altered 3D chromatin structure permits inversional recombination at theScience advances · 2020Article
- Genome Topology Control of Antigen Receptor Gene Assembly.Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- Dynamic 3D Locus Organization and Its Drivers Underpin Immunoglobulin Recombination.Frontiers in immunology · 2020Review
- Two Successive Inversional Vβ Rearrangements on a SingleJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- The murine IgH locus contains a distinct DNA sequence motif for the chromatin regulatory factor CTCF.The Journal of biological chemistry · 2019Article
- Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions.Nature communications · 2019Article
- New insights emerge as antibody repertoire diversification meets chromosome conformation.F1000Research · 2019Review
- Diversification of the TCR β Locus VImmunoHorizons · 2018Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Ig heavy chain (IgH) variable region exons are assembled from V, D, and J gene segments during early B-lymphocyte differentiation. A several megabase region at the "distal" end of the mouse IgH locus (Igh) contains hundreds of V(H)s, separated by an intergenic region from Igh Ds, J(H)s, and constant region exons. Diverse primary Igh repertoires are generated by joining Vs, Ds, and Js in different combinations, with a given B cell productively assembling only one combination. The intergenic control region 1 (IGCR1) in the V(H)-to-D intergenic region regulates Igh V(D)J recombination in the contexts of developmental order, lineage specificity, and feedback from productive rearrangements. IGCR1 also diversifies IgH repertoires by balancing proximal and distal V(H) use. IGCR1 functions in all these regulatory contexts by suppressing predominant rearrangement of D-proximal V(H)s. Such IGCR1 functions were neutralized by simultaneous mutation of two CCCTC-binding factor (CTCF)-binding elements (CBE1 and CBE2) within it. However, it was unknown whether only one CBE mediates IGCR1 functions or whether both function in this context. To address these questions, we generated mice in which either IGCR1 CBE1 or CBE2 was replaced with scrambled sequences that do not bind CTCF. We found that inactivation of CBE1 or CBE2 individually led to only partial impairment of various IGCR1 functions relative to the far greater effects of inactivating both binding elements simultaneously, demonstrating that they function cooperatively to achieve full IGCR1 regulatory activity. Based on these and other findings, we propose an orientation-specific looping model for synergistic CBE1 and CBE2 functions.
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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.