Noncoding transcription controls downstream promoters to regulate Tcell receptor recombination

The T early a (TEA) promoter in the murine Tcra locus generates noncoding transcripts that extend across the 65kb Ja 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 Ja promoters, and can similarly instruct alterations in Ja chromatin structure and Ja recombination. TEA transcription activates promoters associated with relatively proximal Ja 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 Va-to-Ja recombination to TEA-proximal Ja segments and promote the ordered usage of the Ja array. The ability of TEA transcription to coordinate the activity of multiple downstream promoters maximizes the biological potential of the Ja array and diversifies the Tcra repertoire. The EMBO Journal (2007) 26, 4380–4390. doi:10.1038/ sj.emboj.7601866; Published online 20 September 2007 Subject Categories: chromatin & transcription; immunology