A discrete chromatin loop in the murine Tcra/Tcrd locus shapes the TCRd and TCRa 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 TCRd and TCRa 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 Dd, Jd and Cd gene segments allows a single Vd segment to frequently contact and rearrange to Dd and Jd segments and dominate the adult TCRd repertoire. Disruption of this loop also narrows the TCRa repertoire, which, we believe, follows as a consequence of the restricted TCRd repertoire. Hence, a single CTCF-mediated chromatin loop directly regulates TCRd diversity and indirectly regulates TCRa diversity. Overall design: Examination of chromatin loops by 4C-seq from 4 viewpoints in two lymphoid cell compartments: CD4-CD8- thymocytes and naïve B splenocytes.