J. Exp. Med., Volume 189, Number 10, May 17, 1999 1669-1678

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

By 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  (pT) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pT 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 gene. We now report that expression of the pT 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 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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Xu, J., Pope, S. D., Jazirehi, A. R., Attema, J. L., Papathanasiou, P., Watts, J. A., Zaret, K. S., Weissman, I. L., Smale, S. T. (2007). Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Proc. Natl. Acad. Sci. USA 104: 12377-12382 [Abstract] [Full Text]  
• Holley-Guthrie, E. A., Seaman, W. T., Bhende, P., Merchant, J. L., Kenney, S. C. (2005). The Epstein-Barr Virus Protein BMRF1 Activates Gastrin Transcription. J. Virol. 79: 745-755 [Abstract] [Full Text]  
• De Bustos, C, Smits, A, Stromberg, B, Collins, V P, Nister, M, Afink, G (2005). A PDGFRA promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas. J. Med. Genet. 42: 31-37 [Abstract] [Full Text]  
• Boopathi, E., Lenka, N., Prabu, S. K., Fang, J.-K., Wilkinson, F., Atchison, M., Giallongo, A., Avadhani, N. G. (2004). Regulation of Murine Cytochrome c Oxidase Vb Gene Expression during Myogenesis: YY-1 AND HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN D-LIKE PROTEIN (JKTBP1) RECIPROCALLY REGULATE TRANSCRIPTION ACTIVITY BY PHYSICAL INTERACTION WITH THE BERF-1/ZBP-89 FACTOR. J. Biol. Chem. 279: 35242-35254 [Abstract] [Full Text]  
• Kim, J., Lee, J., Yadav, N., Wu, Q., Carter, C., Richard, S., Richie, E., Bedford, M. T. (2004). Loss of CARM1 Results in Hypomethylation of Thymocyte Cyclic AMP-regulated Phosphoprotein and Deregulated Early T Cell Development. J. Biol. Chem. 279: 25339-25344 [Abstract] [Full Text]  
• Merchant, J. L., Bai, L., Okada, M. (2003). ZBP-89 Mediates Butyrate Regulation of Gene Expression. J. Nutr. 133: 2456S-2460 [Abstract] [Full Text]  
• Zhang, X., Diab, I. H., Zehner, Z. E. (2003). ZBP-89 represses vimentin gene transcription by interacting with the transcriptional activator, Sp1. Nucleic Acids Res 31: 2900-2914 [Abstract] [Full Text]  
• Tremblay, M., Herblot, S., Lecuyer, E., Hoang, T. (2003). Regulation of pTalpha Gene Expression by a Dosage of E2A, HEB, and SCL. J. Biol. Chem. 278: 12680-12687 [Abstract] [Full Text]  
• Pinkas, J., Leder, P. (2002). MEK1 Signaling Mediates Transformation and Metastasis of EpH4 Mammary Epithelial Cells Independent of an Epithelial to Mesenchymal Transition. Cancer Res. 62: 4781-4790 [Abstract] [Full Text]  
• Carleton, M., Haks, M. C., Smeele, S. A. A., Jones, A., Belkowski, S. M., Berger, M. A., Linsley, P., Kruisbeek, A. M., Wiest, D. L. (2002). Early Growth Response Transcription Factors Are Required for Development of CD4-CD8- Thymocytes to the CD4+CD8+ Stage. J. Immunol. 168: 1649-1658 [Abstract] [Full Text]  
• Reizis, B., Leder, P. (2002). Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway. Genes Dev. 16: 295-300 [Abstract] [Full Text]  
• Keates, A. C., Keates, S., Kwon, J. H., Arseneau, K. O., Law, D. J., Bai, L., Merchant, J. L., Wang, T. C., Kelly, C. P. (2001). ZBP-89, Sp1, and Nuclear Factor-kappa B Regulate Epithelial Neutrophil-activating Peptide-78 Gene Expression in Caco-2 Human Colonic Epithelial Cells. J. Biol. Chem. 276: 43713-43722 [Abstract] [Full Text]  
• Reizis, B., Leder, P. (2001). The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor {alpha} Gene in Immature T Lymphocytes. J. Exp. Med. 194: 979-990 [Abstract] [Full Text]  
• Takeuchi, A., Yamasaki, S., Takase, K., Nakatsu, F., Arase, H., Onodera, M., Saito, T. (2001). E2A and HEB Activate the Pre-TCR{alpha} Promoter During Immature T Cell Development. J. Immunol. 167: 2157-2163 [Abstract] [Full Text]  
• Bai, L., Merchant, J. L. (2000). Transcription Factor ZBP-89 Cooperates with Histone Acetyltransferase p300 during Butyrate Activation of p21waf1 Transcription in Human Cells. J. Biol. Chem. 275: 30725-30733 [Abstract] [Full Text]  
• Yamada, A., Takaki, S., Hayashi, F., Georgopoulos, K., Perlmutter, R. M., Takatsu, K. (2001). Identification and Characterization of a Transcriptional Regulator for the lck Proximal Promoter. J. Biol. Chem. 276: 18082-18089 [Abstract] [Full Text]  
• Ficzycz, A., Eskiw, C., Meyer, D., Marley, K. E., Hurt, M., Ovsenek, N. (2001). Expression, Activity, and Subcellular Localization of the Yin Yang 1 Transcription Factor in Xenopus Oocytes and Embryos. J. Biol. Chem. 276: 22819-22825 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS