A T-Cell-Specific Transcriptional Enhancer Element 3′ of Cα in the Human T-Cell Receptor α Locus

A transcriptional enhancer element has been identified 4.5 kilobases 3′ of Cα (constant region α chain) in the human T-cell receptor (TCR) α -chain locus. This enhancer is active on both a TCR Vα (variable region α chain) promoter and the minimal simian virus 40 promoter in TCR α /β Jurkat and EL4 cells but is inactive on a Vα promoter in human TCR γ /δ PEER and Molt-13 cells, clone 13 B cells, and HeLa fibroblasts. The enhancer has been localized to a 116-base-pair BstXI/Dra I restriction enzyme fragment, which lacks immunoglobulin octamer and κ B enhancer motifs but does contain a consensus cAMP-response element (CRE). DNase I footprint analyses demonstrated that the minimal enhancer contains two binding sites for Jurkat nuclear proteins. One of these sites corresponds to the CRE, while the other does not correspond to a known transcriptional enhancer motif. These data support a model in which TCR α gene transcription is regulated by a unique set of cis-acting sequences and trans-acting factors, which are differentially active in cells of the TCR α /β lineage. In addition, the TCR α enhancer may play a role in activating oncogene expression in T-lymphoblastoid tumors that have previously been shown to display chromosomal translocations into the human TCR α locus.