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E protein binding at the Tcra enhancer promotes Tcra repertoire diversity

ABSTRACT: E protein binding at the Tcra enhancer promotes Tcra repertoire diversity

PROVIDER: PRJNA943495 | ENA |

REPOSITORIES: ENA

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E protein binding at the Tcra enhancer promotes Tcra repertoire diversity

Project description:The Tcra gene enhancer (Eα) is required for Tcra rearrangment. Our study assesses the role of E protein binding at Eα. Tcra repertoire sequencing was used to determine whether loss of Eα E protein binding sites alters recombination at Tcra.

2023-03-16 | GSE227164 | GEO

E protein binding at the <i>Tcra</i> enhancer promotes <i>Tcra</i> repertoire diversity.

Project description:V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins are known regulators of DP thymocyte development and have three identified binding sites in Eα. To understand the contribution of E proteins to Eα function, mutants lacking one or two of the respective binding sites were generated. The double-binding site mutant displayed a partial block at the positive selection stage of αβ T cell development. Further investigation revealed loss of germline transcription within the Tcra locus at the Jα array, along with dysregulated primary and impaired secondary Vα-Jα rearrangement. Eα E protein binding increases Tcra locus accessibility and regulates TCRα recombination, thus directly promoting Tcra repertoire diversity.

| S-EPMC10358851 | biostudies-literature

Tcrd rearrangement redirects a processive Tcra recombination program to expand the Tcra repertoire

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

Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire

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

A role of the CTCF binding site at enhancer Ea in Tcra rearrangement

Project description:We found that the CTCF binding site (named as EACBE) at the enhancer Eα of Tcra is essential for normal Tcra rearrangement.The EACBE deletion impaired the TAD structure of the 3’ region of the Tcra/d locus and the interactions between the proximal Vα genes and the Jα genes without changing the accessibility of the Jα array.

2020-02-13 | GSE145147 | GEO

Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire

Project description:Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire

| PRJNA772186 | ENA

ROR t directs upregulation of RAG gene expression in DP thymocytes and serves as a multi-faceted regulator of the Tcra repertoire.

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

A discrete chromatin loop in the murine Tcra/Tcrd locus shapes the TCRδ and TCRα repertoires

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

A role of the CTCF binding site at enhancer Ea in Tcra rearrangement

Project description:A role of the CTCF binding site at enhancer Ea in Tcra rearrangement

| PRJNA606188 | ENA

A discrete chromatin loop in the murine Tcra/Tcrd locus shapes the TCRδ and TCRα repertoires

2015-08-10 | GSE67442 | GEO