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- W4313356778 abstract "Abstract In DP thymocytes, primary TCRα rearrangements are restricted to proximal Vα segments at the 3’ end of the Tcra/d locus. We have shown that this restricted Vα usage is supported by a 3’ contracted and 5’ decontracted conformation of Tcra/d. Secondary rearrangement, however, generates a far more diverse pool of Vα-Jα pairings. To investigate the structure the 5’ end of the locus might adopt after primary rearrangement, we performed 3D-FISH on Tcra/d alleles engineered to mimic a natural TRAV17-TRAJ57 rearrangement. We found that the artificially rearranged Tcra/d alleles were markedly contracted at the 5’ end relative to unrearranged Tcra/d. Notably, we observed a similar 5’ end contraction of the locus in CTCF-deficient DP thymocytes with unrearranged Tcra/d. This led us to hypothesize that loss of a critical CTCF binding site as a result of primary rearrangement might promote the 5’ end contraction. Knockout of the T early alpha promoter (TEA), but not other CTCF-bound elements in the region deleted by primary rearrangement, resulted in 5’ contraction of Tcra/d. These data suggest that diversity in secondary TCRα rearrangements is supported by contraction of the whole length of Tcra/d, and that CTCF binding by TEA plays a critical role in enforcing a 5’ decontracted conformation for primary rearrangement. Using 4C, we are now working to understand specific changes in long-range DNA contacts between pre- and post-rearrangement alleles." @default.
- W4313356778 created "2023-01-06" @default.
- W4313356778 creator A5023406972 @default.
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- W4313356778 date "2015-05-01" @default.
- W4313356778 modified "2023-09-23" @default.
- W4313356778 title "The T cell receptor alpha/delta locus adopts distinct contracted conformations during primary and secondary T cell receptor α rearrangement (HEM2P.242)" @default.
- W4313356778 doi "https://doi.org/10.4049/jimmunol.194.supp.51.12" @default.
- W4313356778 hasPublicationYear "2015" @default.
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