The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/5/1669/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1669-1678

Articles

Expression of the Mouse Pre-T Cell Receptor {alpha} Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer

Boris Reizis and Philip Leder

From the Department of Genetics and the Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115

The pre-T cell receptor {alpha} (pT{alpha}) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pT{alpha} gene is one of the earliest markers of the T cell lineage and occurs exclusively in pre-T cells. To investigate the molecular basis of thymocyte-specific gene expression, we searched for the genomic elements regulating transcription of the mouse pT{alpha} gene. We now report that expression of the pT{alpha} gene is primarily controlled by an upstream genomic region, which can drive thymocyte-specific expression of a marker gene in transgenic mice. Within this region, we have identified two specific DNase-hypersensitive sites corresponding to a proximal promoter and an upstream transcriptional enhancer. The pT{alpha} enhancer appears to function preferentially in pre-T cell lines and binds multiple nuclear factors, including YY1. The enhancer also contains two G-rich stretches homologous to a critical region of the thymocyte-specific lck proximal promoter. Here we show that these sites bind a common nuclear factor and identify it as the zinc finger protein ZBP-89. Our data establish a novel experimental model for thymocyte-specific gene expression and suggest an important role for ZBP-89 in T cell development.

Key Words: transcription • T lymphocytes • YY1 • Sp1 • ZBP-89

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

B. Reizis is supported by the Cancer Research Institute Postdoctoral Fellowship.

Abbreviations used: DHS, DNase-hypersensitive site; EMSA, electrophoretic mobility shift assay; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; pT{alpha}, pre-TCR-{alpha}; UTR, untranslated region.


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