Developmental Regulation of  VDJ Recombination By the Core Fragment of the T Cell Receptor α Enhancer

The role of T cell receptor α enhancer (E_α) cis-acting elements in the developmental regulation of VDJ recombination at the TCR α/δ locus was examined in transgenic mice containing variants of a minilocus VDJ recombination substrate. We demonstrate that the 116-bp Tα1,2 core enhancer fragment of the 1.4-kb E_α is sufficient to activate the enhancer-dependent step of minilocus rearrangement, and that within Tα1,2, intact binding sites for TCF/LEF and Ets family transcription factors are essential. Although minilocus rearrangement under the control of the 1.4-kb E_α initiates at fetal day 16.5 and is strictly limited to αβ T cells, we find that rearrangement under the control of Tα1,2 initiates slightly earlier during ontogeny and occurs in both γδ and αβ T cells. We conclude that the core fragment of E_α can establish accessibility to the recombinase in developing thymocytes in vivo in a fashion that is dependent on the binding of TCF/LEF and Ets family transcription factors, but that these and other factors that bind to the E_α core cannot account for the precise developmental onset of accessibility that is provided by the intact E_α. Rather, our data suggests a critical role for factors that bind E_α outside of the core Tα1,2 region in establishing the precise developmental onset of TCR α rearrangement in vivo.