ROR??t directs upregulation of RAG gene expression in DP thymocytes and serves as a multi-faceted regulator of the Tcra repertoire.

Naik et al. show that RAG gene upregulation in DP Thymocytes is controlled by DPASE, a DP-specific open chromatin region in RAG locus. Reduced RAG expression in DPASE KO mice result delayed and incomplete Tcra recombination. Transcription factor RORyt binds to DPASE and Tcra enhancer to regulate Tcra recombination in DP thymocytes. Overall design: High-throughput sequencing was used to analyze Tcra repertoire from RNA purified from sorted DP thymocytes from groups of 2 mice bearing either wild-type or DPASE KO mice.