ArticleThe Journal of experimental medicine2016
Orientation-specific RAG activity in chromosomal loop domains contributes to Tcrd V(D)J recombination during T cell development.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination.Cell reports · 2025Article
- ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination.Science advances · 2024Article
- DNA-PKcs suppresses illegitimate chromosome rearrangements.Nucleic acids research · 2024Article
- Locus folding mechanisms determine modes of antigen receptor gene assembly.The Journal of experimental medicine · 2024Article
- FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2023Article
- FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.bioRxiv : the preprint server for biology · 2023Article
- Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.The Journal of experimental medicine · 2022Article
- Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks atJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- V(D)J Recombination: Recent Insights in Formation of the Recombinase Complex and Recruitment of DNA Repair Machinery.Frontiers in cell and developmental biology · 2022Review
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- Ku70 suppresses alternative end joining in G1-arrested progenitor B cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- 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
- Enhancers as regulators of antigen receptor loci three-dimensional chromatin structure.Transcription · 2020Review
- Two Successive Inversional Vβ Rearrangements on a SingleJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire.Cell reports · 2019Article
- The murine IgH locus contains a distinct DNA sequence motif for the chromatin regulatory factor CTCF.The Journal of biological chemistry · 2019Article
- Article
- Epigenetic and transcriptional mechanisms for the regulation of IL-10.Seminars in immunology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
T cell antigen receptor δ (Tcrd) variable region exons are assembled by RAG-initiated V(D)J recombination events in developing γδ thymocytes. Here, we use linear amplification-mediated high-throughput genome-wide translocation sequencing (LAM-HTGTS) to map hundreds of thousands of RAG-initiated Tcrd D segment (Trdd1 and Trdd2) rearrangements in CD4(-)CD8(-) double-negative thymocyte progenitors differentiated in vitro from bone marrow-derived hematopoietic stem cells. We find that Trdd2 joins directly to Trdv, Trdd1, and Trdj segments, whereas Trdd1 joining is ordered with joining to Trdd2, a prerequisite for further rearrangement. We also find frequent, previously unappreciated, Trdd1 and Trdd2 rearrangements that inactivate Tcrd, including sequential rearrangements from V(D)J recombination signal sequence fusions. Moreover, we find dozens of RAG off-target sequences that are generated via RAG tracking both upstream and downstream from the Trdd2 recombination center across the Tcrd loop domain that is bounded by the upstream INT1-2 and downstream TEA elements. Disruption of the upstream INT1-2 boundary of this loop domain allows spreading of RAG on- and off-target activity to the proximal Trdv domain and, correspondingly, shifts the Tcrd V(D)J recombination landscape by leading to predominant V(D)J joining to a proximal Trdv3 pseudogene that lies just upstream of the normal boundary.
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Registered trials
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