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Enhancer
By
From the Department of Immunology, Duke University Medical Center, Durham,
North Carolina 27710
The role of T cell receptor 
enhancer (E
) cis-acting elements in the developmental regulation
of VDJ recombination at the TCR /
locus was examined in transgenic mice containing variants of a minilocus VDJ recombination substrate. We demonstrate that the 116-bp T1,2
core enhancer fragment of the 1.4-kb E is sufficient to activate the enhancer-dependent step
of minilocus rearrangement, and that within T1,2, 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 initiates at fetal day 16.5 and is strictly limited to 
T cells, we find that rearrangement under the control of T1,2 initiates slightly earlier during ontogeny and occurs in
both 
and T cells. We conclude that the core fragment of E 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 core cannot account for the precise developmental onset of accessibility that is provided by the intact E. Rather, our data suggests a critical role for factors that bind E outside
of the core T1,2 region in establishing the precise developmental onset of TCR rearrangement in vivo.
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