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Publication : Developmental regulation of VDJ recombination by the core fragment of the T cell receptor alpha enhancer.

First Author  Roberts JL Year  1997
Journal  J Exp Med Volume  185
Issue  1 Pages  131-40
PubMed ID  8996249 Mgi Jnum  J:330514
Mgi Id  MGI:7378768 Doi  10.1084/jem.185.1.131
Citation  Roberts JL, et al. (1997) Developmental regulation of VDJ recombination by the core fragment of the T cell receptor alpha enhancer. J Exp Med 185(1):131-40
abstractText  The role of T cell receptor alpha enhancer (E alpha) cis-acting elements in the developmental regulation of VDJ recombination at the TCR alpha/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 sufficient to activate the enhancer-dependent step of minilocus rearrangement, and that within T alpha 1,2, 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 alpha initiates at fetal day 16.5 and is strictly limited to alpha beta T cells, we find that rearrangement under the control of T alpha 1,2 initiates slightly earlier during ontogeny and occurs in both gamma delta and alpha beta T cells. We conclude that the core fragment of E alpha 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 alpha core cannot account for the precise developmental onset of accessibility that is provided by the intact E alpha. Rather, our data suggests a critical role for factors that bind E alpha outside of the core T alpha 1,2 region in establishing the precise developmental onset of TCR alpha rearrangement in vivo.
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