ArticleThe Journal of experimental medicine1999
Positive and negative regulation of V(D)J recombination by the E2A proteins.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 130 citations in OpenAlex.
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- Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.The Journal of experimental medicine · 2022Article
- Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.Frontiers in immunology · 2022Article
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- The divergence between T cell and innate lymphoid cell fates controlled by E and Id proteins.Frontiers in immunology · 2022Review
- Do Molecular Profiles of PrimaryFrontiers in endocrinology · 2021Article
- Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions.Nature communications · 2019Article
- The development of T cells from stem cells in mice and humans.Future science OA · 2017Review
- Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.Advances in immunology · 2016Review
- YY1 controls Igκ repertoire and B-cell development, and localizes with condensin on the Igκ locus.The EMBO journal · 2013Article
- Long-distance regulation of fetal V(δ) gene segment TRDV4 by the Tcrd enhancer.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Molecular aspects of epithelial γδ T cell regulation.Trends in immunology · 2011Review
- Regulation of antigen receptor gene assembly by genetic-epigenetic crosstalk.Seminars in immunology · 2010Review
- Expanding roles for ThPOK in thymic development.Immunological reviews · 2010Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A key feature of B and T lymphocyte development is the generation of antigen receptors through the rearrangement and assembly of the germline variable (V), diversity (D), and joining (J) gene segments. However, the mechanisms responsible for regulating developmentally ordered gene rearrangements are largely unknown. Here we show that the E2A gene products are essential for the proper coordinated temporal regulation of V(D)J rearrangements within the T cell receptor (TCR) gamma and delta loci. Specifically, we show that E2A is required during adult thymocyte development to inhibit rearrangements to the gamma and delta V regions that normally recombine almost exclusively during fetal thymocyte development. The continued rearrangement of the fetal Vgamma3 gene segment in E2A-deficient adult thymocytes correlates with increased levels of Vgamma3 germline transcripts and increased levels of double-stranded DNA breaks at the recombination signal sequence bordering Vgamma3. Additionally, rearrangements to a number of Vgamma and Vdelta gene segments used predominantly during adult development are significantly reduced in E2A-deficient thymocytes. Interestingly, at distinct stages of T lineage development, both the increased and decreased rearrangement of particular Vdelta gene segments is highly sensitive to the dosage of the E2A gene products, suggesting that the concentration of the E2A proteins is rate limiting for the recombination reaction involving these Vdelta regions.
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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.