The expression of the pre-T cell receptor α (pTa) gene occurs exclusively in immature T lymphocytes and is regulated by poorly defined mechanisms. We have analyzed the role of the upstream enhancer in pTa expression using conventional and bacterial artificial chromosome (BAC) reporter transgenes. The deletion of the enhancer completely abolished the expression of pTa BAC reporter in transgenic mice. Conversely, the combination of pTa enhancer and promoter targeted transgenes specifically to immature thymocytes, recapitulating the expression pattern of pTa. The core enhancer is conserved between mice and humans and contains a critical binding site for the transcription factor c-Myb. We also show that pTa promoter contains a conserved tandem E box site activated by E protein, HEB. These data establish the enhancer as a critical element regulating pTa gene expression and identify additional targets for c-Myb and E proteins in T cell development.
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1 October 2001
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October 01 2001
The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor α Gene in Immature T Lymphocytes
Boris Reizis,
Boris Reizis
aDepartment of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115
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Philip Leder
Philip Leder
aDepartment of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115
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Boris Reizis
aDepartment of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115
Philip Leder
aDepartment of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115
Abbreviations used in this paper: APC, allophycocyanin; BAC, bacterial artificial chromosome; bHLH, basic helix-loop-helix; DBD, DNA-binding domain; DN, double-negative; DP, double-positive; EGFP, enhanced green fluorescent protein; EMSA, electrophoretic mobility shift assay; ISP, immature single-positive; pTa, pre-T cell receptor α; SP, single-positive.
Received:
February 13 2001
Revision Requested:
August 07 2001
Accepted:
August 21 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 194 (7): 979–990.
Article history
Received:
February 13 2001
Revision Requested:
August 07 2001
Accepted:
August 21 2001
Citation
Boris Reizis, Philip Leder; The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor α Gene in Immature T Lymphocytes. J Exp Med 1 October 2001; 194 (7): 979–990. doi: https://doi.org/10.1084/jem.194.7.979
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