Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA279956 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Tcra/Tcrd locus undergoes V(D)J recombination in CD4−CD8− double-negative (DN) thymocytes and CD4+CD8+ double-positive (DP) thymocytes to generate diverse TCRδ and TCRα repertoires, respectively. Here we reveal a Tcra/Tcrd locus chromatin interaction network in DN thymocytes that is formed by interactions between CTCF-binding elements (CBEs). Disruption of a discrete chromatin loop encompassing the Dδ, Jδ and Cδ gene segments allows a single Vδ segment to frequently contact and rearrange to Dδ and Jδ segments and dominate the adult TCRδ repertoire. Disruption of this loop also narrows the TCRα repertoire, which, we believe, follows as a consequence of the restricted TCRδ repertoire. Hence, a single CTCF-mediated chromatin loop directly regulates TCRδ diversity and indirectly regulates TCRα diversity. Examination of chromatin loops by 4C-seq from 4 viewpoints in two lymphoid cell compartments: CD4-CD8- thymocytes and naïve B splenocytes.
2015-08-10 | E-GEOD-67442 | biostudies-arrayexpress
Project description:The Tcra/Tcrd locus undergoes V(D)J recombination in CD4−CD8− double-negative (DN) thymocytes and CD4+CD8+ double-positive (DP) thymocytes to generate diverse TCRδ and TCRα repertoires, respectively. Here we reveal a Tcra/Tcrd locus chromatin interaction network in DN thymocytes that is formed by interactions between CTCF-binding elements (CBEs). Disruption of a discrete chromatin loop encompassing the Dδ, Jδ and Cδ gene segments allows a single Vδ segment to frequently contact and rearrange to Dδ and Jδ segments and dominate the adult TCRδ repertoire. Disruption of this loop also narrows the TCRα repertoire, which, we believe, follows as a consequence of the restricted TCRδ repertoire. Hence, a single CTCF-mediated chromatin loop directly regulates TCRδ diversity and indirectly regulates TCRα diversity.
2015-08-10 | GSE67442 | GEO
Project description:The Tcra-Tcrd locus undergoes Tcrd rearrangement in DN thymocytes followed by primary and secondary Tcra rearrangements in DP thymocytes. Here we reveal the mechanisms underpinning combinatorial diversity in the Tcra repertoire. We show that V-alpha and J-alpha segments on individual Tcra alleles are used in stepwise and coordinated proximal-to-distal progressions during primary and secondary rearrangements, substantially constraining combinatorial diversity. Notably, Tcrd recombination in DN thymocytes diversifies the Tcra repertoire by truncating the V-alpha array to permit otherwise disfavored V-J combinations. Such diversification is important, because Trav1-Traj33+ mucosa-associated invariant T cells are depleted when Tcrd rearrangement is impaired. Our results reveal an important biological advantage conferred by the nested organization of Tcrd and Tcra gene segments.
2017-06-06 | GSE95826 | GEO
Project description:Chromatin looping mediated by the CCCTC binding factor CTCF regulates V(D)J recombination at antigen receptor loci. CTCF-mediated looping can influence recombination signal sequence accessibility by regulating enhancer activation of germline promoters. CTCF-mediated looping has also been shown to limit directional tracking of the RAG recombinase along chromatin, and to regulate through-space interactions between recombination signal sequences, independent of the RAG recombinase. However, in all prior instances in which CTCF-mediated looping was shown to influence V(D)J recombination, it was not possible to fully resolve the relative contributions to the V(D)J recombination phenotype of changes in accessibility, RAG-tracking, and RAG-independent long-distance interactions. Here, to assess mechanisms by which CTCF-mediated looping can impact V(D)J recombination, we introduced an ectopic CTCF binding element (CBE) immediately downstream of Eδ in the murine Tcra-Tcrd locus. The ectopic CBE impaired inversional rearrangement of Trdv5 in the absence of measurable effects on Trdv5 transcription and chromatin accessibility. Moreover, although the ectopic CBE limited directional RAG tracking from the Tcrd recombination center, such tracking cannot account for Trdv5-to-Trdd2 inversional rearrangement. Rather, the defect in Trdv5 rearrangement could only be attributed to a reconfigured chromatin loop organization that limited RAG-independent through-space interactions between the Trdv5 and Trdd2 RSSs. We conclude that CTCF can regulate V(D)J recombination by segregating RSSs into distinct loop domains and inhibiting RSS synapsis, independent of any effects on transcription, RSS accessibility and RAG tracking. RAG-initiatd Tcrd D segment rearrangements in developing thymocytes were generated by deep sequencing using illumine Miseq
2016-09-02 | E-GEOD-81351 | biostudies-arrayexpress
Project description:Dauphars et al. show that prior Tcrd rearrangement is essential for a combinatorially diverse Tcra repertoire in mouse thymocytes. Trav15-dv6 family Tcrd rearrangements are critical for Tcra repertoire formation because of their central and distal locations in the Va-Vd array.
2021-10-21 | GSE186044 | GEO
Project description:Chromatin looping mediated by the CCCTC binding factor CTCF regulates V(D)J recombination at antigen receptor loci. CTCF-mediated looping can influence recombination signal sequence accessibility by regulating enhancer activation of germline promoters. CTCF-mediated looping has also been shown to limit directional tracking of the RAG recombinase along chromatin, and to regulate through-space interactions between recombination signal sequences, independent of the RAG recombinase. However, in all prior instances in which CTCF-mediated looping was shown to influence V(D)J recombination, it was not possible to fully resolve the relative contributions to the V(D)J recombination phenotype of changes in accessibility, RAG-tracking, and RAG-independent long-distance interactions. Here, to assess mechanisms by which CTCF-mediated looping can impact V(D)J recombination, we introduced an ectopic CTCF binding element (CBE) immediately downstream of Eδ in the murine Tcra-Tcrd locus. The ectopic CBE impaired inversional rearrangement of Trdv5 in the absence of measurable effects on Trdv5 transcription and chromatin accessibility. Moreover, although the ectopic CBE limited directional RAG tracking from the Tcrd recombination center, such tracking cannot account for Trdv5-to-Trdd2 inversional rearrangement. Rather, the defect in Trdv5 rearrangement could only be attributed to a reconfigured chromatin loop organization that limited RAG-independent through-space interactions between the Trdv5 and Trdd2 RSSs. We conclude that CTCF can regulate V(D)J recombination by segregating RSSs into distinct loop domains and inhibiting RSS synapsis, independent of any effects on transcription, RSS accessibility and RAG tracking.
2016-09-02 | GSE81351 | GEO
Project description:The generation of highly diverse antigen receptors in T and B lymphocytes relies on V(D)J recombination. The enhancer Eα has been implicated in regulating the accessibility of Vα and Jα genes through long-range interactions during T cell antigen receptor gene Tcra rearrangements. However, direct evidence for Eα physically mediating the interaction of Vα and Jα genes is still lacking. In this study, we utilized the 3C-HTGTS assay, a chromatin interaction technique based on 3C, to analyze the higher-order chromatin structure of the Tcra locus. Our analysis revealed the presence of sufficient information in the 3C-HTGTS data to detect multi-way contacts. Three-way contact analysis of the Tcra locus demonstrated the co-occurrence of the proximal Jα genes, Vα genes, and Eα in CD4+CD8+ double-positive thymocytes. Notably, the INT2-TEAp loop emerged as a prominent structure likely responsible for bringing the proximal Jα genes and the Vα genes into proximity. Moreover, the enhancer Eα utilizes this loop to establish physical proximity with the proximal Vα gene region. This study provides insights into the higher-order chromatin structure of the Tcra locus, shedding light on the spatial organization of chromatin and its impact on V(D)J recombination.
2022-11-28 | GSE214918 | GEO
Project description:Tcrd rearrangement redirects a processive Tcra recombination program to expand the Tcra repertoire
| PRJNA378534 | ENA
Project description:Topologically Associating Domains (TADs) partition the genome into self-interacting regions through boundaries. Chromatin configuration plays a crucial role in TCR gene rearrangements, thereby affecting repertoire diversity. To assess the dynamics of chromatin boundaries within TCR genes, we conducted Hi-C assays on double-negative (DN) and double-positive (DP) cells from RAG-deficient mice. A chromatin boundary at the 3' end of the Tcrb locus observed in DN cells dissipated in DP cells, thereby altering interactions between the main Vβ cluster and the recombination center. Additionally, the INTs boundary in the Tcra-Tcrd locus disappeared in DP cells, leading to enhanced interactions between the proximal Vα region and recombination center at the Jα segments. Subsequent analysis revealed that the disappearance of boundaries was not attributable to diminished CTCF binding but rather heightened activity within these regions. This study illuminates the developmental dynamics of TAD boundaries in TCR genes, enriching our understanding of their evolving nature.
2024-04-27 | GSE265888 | GEO
Project description:Naik et al. show that RAG gene upregulation in DP Thymocytes is controlled by DPASE, a DP-specific open chromatin region in RAG locus. Reduced RAG expression in DPASE KO mice result delayed and incomplete Tcra recombination. Transcription factor RORyt binds to DPASE and Tcra enhancer to regulate Tcra recombination in DP thymocytes.
2023-02-20 | GSE225627 | GEO