The pre-T cell receptor α (pTα) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pTα 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 pTα gene. We now report that expression of the pTα 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 pTα 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.
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17 May 1999
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May 17 1999
Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
Boris Reizis,
Boris Reizis
From the Department of Genetics and the Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115
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Philip Leder
Philip Leder
From the Department of Genetics and the Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115
Search for other works by this author on:
Boris Reizis
From the Department of Genetics and the Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115
Philip Leder
From the Department of Genetics and the Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115
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: [email protected]
B. Reizis is supported by the Cancer Research Institute Postdoctoral Fellowship.
Received:
March 09 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (10): 1669–1678.
Article history
Received:
March 09 1999
Citation
Boris Reizis, Philip Leder; Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer . J Exp Med 17 May 1999; 189 (10): 1669–1678. doi: https://doi.org/10.1084/jem.189.10.1669
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