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Specification of V? and V? usage by Tcra/Tcrd locus V gene segment promoters.

ABSTRACT: The Tcra/Tcrd locus undergoes V-D?-J? rearrangement in CD4(-)CD8(-) thymocytes to form the TCR? chain of the ?? TCR and V-J? rearrangement in CD4(+)CD8(+) thymocytes to form the TCR?-chain of the ?? TCR. Most V segments in the locus participate in V-J? rearrangement, but only a small and partially overlapping subset participates in V-D?-J? rearrangement. What specifies any particular Tcra/Tcrd locus V gene segment as a V?, a V?, or both is currently unknown. We tested the hypothesis that V segment usage is specified by V segment promoter-dependent chromatin accessibility in developing thymocytes. TRAV15/DV6 family V gene segments contribute to both the Tcrd and the Tcra repertoires, whereas TRAV12 family V gene segments contribute almost exclusively to the Tcra repertoire. To understand whether the TRAV15/DV6 promoter region specifies TRAV15/DV6 as a V?, we used gene targeting to replace the promoter region of a TRAV12 family member with one from a TRAV15/DV6 family member. The TRAV15/DV6 promoter region conferred increased germline transcription and histone modifications to TRAV12 in double-negative thymocytes and caused a substantial increase in usage of TRAV12 in Tcrd recombination events. Our results demonstrate that usage of TRAV15/DV6 family V gene segments for Tcrd recombination in double-negative thymocytes is regulated, at least in part, by intrinsic features of TRAV15/DV6 promoters, and argue that Tcra/Tcrd locus V? gene segments are defined by their local chromatin accessibility in CD4(-)CD8(-) thymocytes.

SUBMITTER: Naik AK 

PROVIDER: S-EPMC4282949 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Specification of Vδ and Vα usage by Tcra/Tcrd locus V gene segment promoters.

Naik Abani Kanta AK   Hawwari Abbas A   Krangel Michael S MS  

Journal of immunology (Baltimore, Md. : 1950) 20141203 2

The Tcra/Tcrd locus undergoes V-Dδ-Jδ rearrangement in CD4(-)CD8(-) thymocytes to form the TCRδ chain of the γδ TCR and V-Jα rearrangement in CD4(+)CD8(+) thymocytes to form the TCRα-chain of the αβ TCR. Most V segments in the locus participate in V-Jα rearrangement, but only a small and partially overlapping subset participates in V-Dδ-Jδ rearrangement. What specifies any particular Tcra/Tcrd locus V gene segment as a Vδ, a Vα, or both is currently unknown. We tested the hypothesis that V segme  ...[more]

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