A discrete chromatin loop in the murine Tcra/Tcrd locus shapes the TCRδ and TCRα repertoires

The Tcra/Tcrd locus undergoes V(D)J recombination in CD4−CD8− double-negative (DN) thymocytes and CD4+CD8+ double-positive (DP) thymocytes to generate diverse TCRδ and TCRα repertoires, respectively. Here we reveal a Tcra/Tcrd locus chromatin interaction network in DN thymocytes that is formed by interactions between CTCF-binding elements (CBEs). Disruption of a discrete chromatin loop encompassing the Dδ, Jδ and Cδ gene segments allows a single Vδ segment to frequently contact and rearrange to Dδ and Jδ segments and dominate the adult TCRδ repertoire. Disruption of this loop also narrows 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. Examination of chromatin loops by 4C-seq from 4 viewpoints in two lymphoid cell compartments: CD4-CD8- thymocytes and naïve B splenocytes.