title: A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRδ and TCRα repertoires.
abstract: The locus encoding the T cell antigen receptor (TCR) α-chain and δ-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 TCRδ repertoires and TCRα 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 TCRδ repertoire. Disruption of this loop also narrowed the TCRα repertoire, which, we believe, followed as a consequence of the restricted TCRδ repertoire. Hence, a single CTCF-mediated chromatin loop directly regulated TCRδ diversity and indirectly regulated TCRα diversity.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Carico
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Shih
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Krangel
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics; D005434:Flow Cytometry; D051379:Mice; D009690:Nucleic Acid Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D002843:Chromatin; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta