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Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232
The tissue- and stage-specific assembly of Ag receptor genes is regulated by transcriptional control elements positioned within Ig and TCR loci. To further understand the role of cis-acting elements in these regulatory mechanisms, we have characterized a transcriptional promoter that drives germline expression of TCRß gene segments in vivo. The activity of this promoter, termed PDß, is restricted to a highly conserved 400-bp region located directly upstream from Dß1-coding sequences. Maximal PDß activity requires a TATA element situated within the Dß1 recombination signal sequences and consensus binding sites for the ubiquitous SP1 and the T cell-specific GATA-3 transcription factors. When linked to active enhancer elements, PDß directs transcription in most cell types; however, the TCRß enhancer (Eß) stimulates PDß function specifically in precursor T lymphocytes. These findings suggest that PDß/Eß interactions may contribute to differential regulation of regions within the TCRß locus during thymocyte development.
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