The role of T cell receptor α enhancer (Eα) 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 Eα 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 Eα 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 Eα 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 Eα core cannot account for the precise developmental onset of accessibility that is provided by the intact Eα. Rather, our data suggests a critical role for factors that bind Eα outside of the core Tα1,2 region in establishing the precise developmental onset of TCR α rearrangement in vivo.
Developmental Regulation of VDJ Recombination By the Core Fragment of the T Cell Receptor α Enhancer
Address correspondence to Michael S. Krangel, Department of Immunology, PO Box 3010, Duke University Medical Center, Durham, NC 27710. The current address of P. Lauzurica is Seccion de Immunologia, Hospital de la Princesa, 28006 Madrid, Spain.
This work was supported by National Institutes of Health grant GM41052. M.S. Krangel is the recipient of American Cancer Society Faculty Research Award FRA-414. J.L. Roberts was supported in part by Public Health Service Training grant CA09058.
1Abbreviations used in this paper: DN, double negative; DP, double positive; Eα, α enhancer; Eδ, δ enhancer; HMG, high mobility group; ISP, immature single positive.
Joseph L. Roberts, Pilar Lauzurica, Michael S. Krangel; Developmental Regulation of VDJ Recombination By the Core Fragment of the T Cell Receptor α Enhancer. J Exp Med 6 January 1997; 185 (1): 131–140. doi: https://doi.org/10.1084/jem.185.1.131
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