A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRδ and TCRα repertoires.
Published
Journal Article
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.
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Duke Authors
Cited Authors
- Chen, L; Carico, Z; Shih, H-Y; Krangel, MS
Published Date
- October 2015
Published In
Volume / Issue
- 16 / 10
Start / End Page
- 1085 - 1093
PubMed ID
- 26258942
Pubmed Central ID
- 26258942
Electronic International Standard Serial Number (EISSN)
- 1529-2916
Digital Object Identifier (DOI)
- 10.1038/ni.3232
Language
- eng
Conference Location
- United States