A LOCUS-CONTROL REGION IN THE T-CELL RECEPTOR ALPHA/DELTA LOCUS

A locus control region (LCR) is a set of cis-acting elements that regulate chromatin accessibility of a gene locus. In the T cell receptor (TCR) alpha/delta locus, an LCR might regulate the differential tissue and developmental expression and the rearrangement of TCR alpha and delta genes. We have localized a region 3' of the TCR alpha/delta locus containing eight T cell-specific nuclease hypersensitive domains (HS-1 to HS-8), which fit the characteristics of an LCR. In transgenic mice, a TCR alpha gene linked to this region is expressed at a high level, independent of the site of integration and correlates with gene copy number. The transgene is expressed in the alpha beta but not the gamma delta T cell subset and is activated at the right time during development. Proper LCR function requires the region containing HS-2 to HS-6. We propose a model of LCR competition to explain the differential regulation of TCR alpha versus delta genes during development.