DEVELOPMENTAL REGULATION OF VDJ RECOMBINATION BY THE CORE FRAGMENT OFTHE T-CELL RECEPTOR-ALPHA ENHANCER

The role of T cell receptor alpha enhancer (E(alpha)) cis-acting eleme nts in the developmental regulation of VDJ recombination ac the TCR al pha/delta locus was examined in transgenic mice containing variants of a minilocus VDJ recombination substrate. We demonstrate: that the 116 -bp T alpha 1,2 core enhancer fragment of the 1.4-kb E(alpha) is suffi cient to activate the enhancer-dependent step of minilocus rearrangeme nt, and that within T alpha 1,2 intact binding sites for TCF/LEF and E ts family transcription factors are essential. Although minilocus rear rangement under the control of the 1.1-kb E(alpha) initiates at fetal day 16.5 and is strictly limited to alpha beta T cells, we find that r earrangement under the control of T alpha 1,2 initiates slightly earli er during ontogeny and occurs in both gamma delta and alpha beta T cel ls. We conclude that the core fragment of E(alpha) can establish acces sibility to the recombinase in developing thymocytes in vivo in a fash ion that is dependent oil the binding of TCF/LEF and Ets family transc ription factors, but that these and other factors that bind to the E(a lpha) core cannot account for the precise developmental onset of acces sibility that is provided by the intact E(alpha). Rather, our data sug gests a critical role for factors that bind E(alpha) outside of the co re T alpha 1,2 region ill establishing the precise developmental onset of TCR alpha rearrangement ill vivo.