Abstract
The Tcra-Tcrd locus undergoes V(D)J recombination in CD4−CD8−double-negative thymocytes and CD4+CD8+ double-positive thymocytes to generate diverse TCRδ and TCRα repertoires, respectively. Here we reveal a Tcra-Tcrd locus chromatin interaction network in double-negative thymocytes that was formed by interactions between CTCF-binding elements. Disruption of a discrete chromatin loop encompassing Tcrd diversity, joining and constant gene segments allowed a single variable gene segment to frequently contact and rearrange to diversity and joining gene segments and dominate the adult TCRδ repertoire. Disruption of this loop also narrowed the TCRα repertoire, which, we believe, follows as a consequence of the restricted TCRδ repertoire. Hence, a single CTCF-mediated chromatin loop directly regulates TCRδ diversity and indirectly regulates TCRα diversity.
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