A locus control region (LCR) is a set of cis-acting elements that regu
late 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 de
lta 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 develop
ment. Proper LCR function requires the region containing HS-2 to HS-6.
We propose a model of LCR competition to explain the differential reg
ulation of TCR alpha versus delta genes during development.