ArticleThe Journal of experimental medicine2015
Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 56 citations in OpenAlex.
- Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination.Cell reports · 2025Article
- Locus folding mechanisms determine modes of antigen receptor gene assembly.The Journal of experimental medicine · 2024Article
- Lineage- and stage-specific activity of antigen receptor gene enhancers during lymphocyte development.Frontiers in epigenetics and epigenomics · 2024Review
- Multiple lineage-specific epigenetic landscapes at the antigen receptor loci.Aging research (Hong Kong, China) · 2023Article
- Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes.Nature communications · 2023Article
- Gene Regulatory Circuits in Innate and Adaptive Immune Cells.Annual review of immunology · 2022Review
- Characterization of transcripts emanating from enhancer Eβ of the murine TCRβ locus.FEBS open bio · 2021Article
- Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function.International journal of molecular sciences · 2020Review
- A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra-Tcrd locus.Nucleic acids research · 2020Article
- Poor quality Vβ recombination signal sequences stochastically enforce TCRβ allelic exclusion.The Journal of experimental medicine · 2020Article
- Altered 3D chromatin structure permits inversional recombination at theScience advances · 2020Article
- DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner.Nature communications · 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
- New insights emerge as antibody repertoire diversification meets chromosome conformation.F1000Research · 2019Review
- Diversification of the TCR β Locus VImmunoHorizons · 2018Article
- A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus.Cell reports · 2018Article
- Sequential Enhancer Sequestration Dysregulates Recombination Center Formation at the IgH Locus.Molecular cell · 2018Article
- Variable Extent of Lineage-Specificity and Developmental Stage-Specificity of Cohesin and CCCTC-Binding Factor Binding Within the Immunoglobulin and T Cell Receptor Loci.Frontiers in immunology · 2018Article
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10 authors at 5 institutions in 2 countries.
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Abstract
Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vβ array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vβ gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers.
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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.