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- W4313356819 startingPage "51.3" @default.
- W4313356819 abstract "Abstract The diversity of antigen receptors on T and B lymphocytes is generated by the assembly of variable (V), diversity (D), and joining (J) gene segments. At the TCRα/δ locus, Vδ-Dδ-Jδ rearrangement occurs in CD4−CD8− double-negative (DN) thymocytes, whereas Vα and Jα are joined in CD4+CD8+ double-positive (DP) thymocytes. We previously showed that CTCF is an important regulator of chromatin conformation and Vα-Jα recombination in DP thymocytes. Here we show that INT1-2, a pair of CTCF-binding elements (CBEs), plays an important role in shaping the TCRδ repertoire in DN thymocytes. INT1-2-/- mice have a restricted TCRδ repertoire with Vδ4 being strongly predominant. Chromatin conformation capture assays showed that INT1-2-deletion disrupts a stable loop between INT2 and TEA CBEs and promotes the formation of new interactions between TEA and CBEs that are upstream of INT1-2. This alteration of chromatin loops disrupts a locus conformation designed to grant diverse Vδ segments an opportunity to pair with Dδ and Jδ segments. Additional analysis of INT1-2-/- DP thymocytes revealed a restricted TCRα repertoire, which we believe occurs as a consequence of the restricted TCRδ repertoire." @default.
- W4313356819 created "2023-01-06" @default.
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- W4313356819 date "2015-05-01" @default.
- W4313356819 modified "2023-09-23" @default.
- W4313356819 title "A CTCF-dependent regulatory element in the mouse TCRα/δ locus shapes the TCRα/δ repertoire (HEM2P.233)" @default.
- W4313356819 doi "https://doi.org/10.4049/jimmunol.194.supp.51.3" @default.
- W4313356819 hasPublicationYear "2015" @default.
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