A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCR? and TCR? repertoires.

ABSTRACT: The locus encoding the T cell antigen receptor (TCR) ?-chain and ?-chain (Tcra-Tcrd) undergoes recombination of its variable-diversity-joining (V(D)J) segments in CD4(-)CD8(-) double-negative thymocytes and CD4(+)CD8(+) double-positive thymocytes to generate diverse TCR? repertoires and TCR? repertoires, respectively. Here we identified a chromatin-interaction network in the Tcra-Tcrd locus in double-negative thymocytes that was formed by interactions between binding elements for the transcription factor CTCF. Disruption of a discrete chromatin loop encompassing the D, J and constant (C) segments of Tcrd allowed a single V segment to frequently contact and rearrange to D and J segments and dominate the adult TCR? repertoire. Disruption of this loop also narrowed the TCR? repertoire, which, we believe, followed as a consequence of the restricted TCR? repertoire. Hence, a single CTCF-mediated chromatin loop directly regulated TCR? diversity and indirectly regulated TCR? diversity.

SUBMITTER: Chen L 

PROVIDER: S-EPMC4575630 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature