Original Article

The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor Gene in Immature T Lymphocytes

Correspondence to: Philip Leder, Dept. of Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Tel:617-432-7667 Fax:617-432 7944 E-mail:leder{at}rascal.med.harvard.edu.

The expression of the pre-T cell receptor (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.

Key Words: transcription, thymus, c-Myb, basic helix-loop-helix proteins, HEB

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