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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE225627 | GEO | 2023/02/20

REPOSITORIES: GEO

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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.

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Expression data from BDC2.5 TCR Tg, preselected Rag-/-.B6 and Rag-/-.NOD.H2b thymocytes upon antigenic stimulation

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

Project description:ROR훾t directs upregulation of RAG gene expression in DP thymocytes and serves as a multi-faceted regulator of the Tcra repertoire.

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

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Project description:The transcription factor Zfp335 is esstential for the survival of post-B-selection DN4 thymocytes. We utilized TCRa repertoire sequencing to assess alterations to survival duration for Zfp335-deficient DP thymocytes.

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