The upstream enhancer is necessary and sufficient for the expression of the pre-T cell receptor alpha gene in immature T lymphocytes.
The expression of the pre-T cell receptor alpha (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.
Reizis
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Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Leder
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D000818:Animals; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D019673:Genes, T-Cell Receptor alpha; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes
D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha