The 3′-Jα Region of the TCRα Locus Bears Gene Regulatory Activity in Thymic and Peripheral T Cells

Much progress has been made in understanding the important cis-mediated controls on mouse TCR alpha gene function, including identification of the E alpha enhancer and TCR alpha locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the E alpha/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5' of the C alpha exons. Using DNase hypersensitivity assays and TCR alpha BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively affects upstream, but not downstream, gene expression. Together, these data indicate the existence of a novel cis-acting regulatory complex that contributes to TCR alpha transgene expression in vivo. The active chromatin sites we discovered within this region would remain in the locus after TCR alpha gene rearrangement, and thus may contribute to endogenous TCR alpha gene activity, particularly in peripheral T cells, where the E alpha element has been found to be inactive.