Noncoding transcription controls downstream promoters to regulate T-cell receptor α recombination

Abstract

The T early α (TEA) promoter in the murine Tcra locus generates noncoding transcripts that extend across the 65 kb Jα array. Here, we have analyzed the significance of TEA transcription for Tcra locus regulation through the targeted introduction of a transcription terminator downstream of the TEA promoter. We demonstrate that noncoding transcription driven by this single promoter can instruct both positively and negatively the activity of downstream Jα promoters, and can similarly instruct alterations in Jα chromatin structure and Jα recombination. TEA transcription activates promoters associated with relatively proximal Jα segments and stimulates histone acetylation, histone methylation and chromatin accessibility in this region. In contrast, at more distal locations, TEA transcription inhibits promoter activity through transcriptional interference and suppresses chromatin accessibility. In combination, these effects target initial Vα-to-Jα recombination to TEA-proximal Jα segments and promote the ordered usage of the Jα array. The ability of TEA transcription to coordinate the activity of multiple downstream promoters maximizes the biological potential of the Jα array and diversifies the Tcra repertoire. © 2007 European Molecular Biology Organization | All Rights Reserved.