ArticleProceedings of the National Academy of Sciences of the United States of America2012
Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 81 citations in OpenAlex.
- Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination.Cell reports · 2025Article
- The insulator EACBE regulates V(D)J recombination of Tcrd gene by modulating chromatin organization.Frontiers in immunology · 2025Article
- Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription.Genome research · 2024Article
- RORγt up-regulates RAG gene expression in DP thymocytes to expand theScience immunology · 2024Article
- Locus folding mechanisms determine modes of antigen receptor gene assembly.The Journal of experimental medicine · 2024Article
- Three-way contact analysis characterizes the higher order organization of the Tcra locus.Nucleic acids research · 2023Article
- Loop stacking organizes genome folding from TADs to chromosomes.Molecular cell · 2023Article
- Elevated enhancer-oncogene contacts and higher oncogene expression levels by recurrent CTCF inactivating mutations in acute T cell leukemia.Cell reports · 2023Article
- Three-dimensional genome organization in immune cell fate and function.Nature reviews. Immunology · 2023Review
- The 3D enhancer network of the developing T cell genome is shaped by SATB1.Nature communications · 2022Article
- The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRβ and TCRα Genes and Influences Development of αβ T Cell Lineages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Super-resolution visualization of chromatin loop folding in human lymphoblastoid cells using interferometric photoactivated localization microscopy.Scientific reports · 2022Article
- Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.The Journal of experimental medicine · 2022Article
- Evolving Views of Long Noncoding RNAs and Epigenomic Control of Lymphocyte State and Memory.Cold Spring Harbor perspectives in biology · 2022Review
- 3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells.Frontiers in immunology · 2022Review
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- Epigenetic strategies to boost CAR T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- The Toolbox for Untangling Chromosome Architecture in Immune Cells.Frontiers in immunology · 2021Review
- Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies.Frontiers in immunology · 2021Review
- SATB1-mediated chromatin landscape in T cells.Nucleus (Austin, Tex.) · 2020Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Antigen receptor locus V(D)J recombination requires interactions between widely separated variable (V), diversity (D), and joining (J) gene segments, but the mechanisms that generate these interactions are not well understood. Here we assessed mechanisms that direct developmental stage-specific long-distance interactions at the Tcra/Tcrd locus. The Tcra/Tcrd locus recombines Tcrd gene segments in CD4(-)CD8(-) double-negative thymocytes and Tcra gene segments in CD4(+)CD8(+) double-positive thymocytes. Initial V(α)-to-J(α) recombination occurs within a chromosomal domain that displays a contracted conformation in both thymocyte subsets. We used chromosome conformation capture to demonstrate that the Tcra enhancer (E(α)) interacts directly with V(α) and J(α) gene segments distributed across this domain, specifically in double-positive thymocytes. Moreover, E(α) promotes interactions between these V(α) and J(α) segments that should facilitate their synapsis. We found that the CCCTC-binding factor (CTCF) binds to E(α) and to many locus promoters, biases E(α) to interact with these promoters, and is required for efficient V(α)-J(α) recombination. Our data indicate that E(α) and CTCF cooperate to create a developmentally regulated chromatin hub that supports V(α)-J(α) synapsis and recombination.
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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.