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Originally published In Press as doi:10.1074/jbc.M209870200 on February 3, 2003

J. Biol. Chem., Vol. 278, Issue 15, 12680-12687, April 11, 2003
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Regulation of pTalpha Gene Expression by a Dosage of E2A, HEB, and SCL*

Mathieu TremblayDagger §, Sabine HerblotDagger , Eric LécuyerDagger ||, and Trang HoangDagger **Dagger Dagger

From the Dagger  Clinical Research Institute of Montréal, Montréal, Québec H2W 1R7, Canada and the ** Departments of Pharmacology and Biochemistry and the Molecular Biology Program, University of Montréal, Montréal, Québec H3C 3J7, Canada

The expression of the pTalpha gene is required for effective selection, proliferation, and survival of beta  T-cell receptor (beta TCR)-expressing immature thymocytes. Here, we have identified two phylogenetically conserved E-boxes within the pTalpha enhancer sequence that are required for optimal enhancer activity and for its stage-specific activity in immature T cells. We have shown that the transcription factors E2A and HEB associate with high affinity to these E-boxes. Moreover, we have identified pTalpha as a direct target of E2A-HEB heterodimers in immature thymocytes because they specifically occupy the enhancer in vivo. In these cells, pTalpha mRNA levels are determined by the presence of one or two functional E2A or HEB alleles. Furthermore, E2A/HEB transcriptional activity is repressed by heterodimerization with SCL, a transcription factor that is turned off in differentiating thymocytes exactly at a stage when pTalpha is up-regulated. Taken together, our observations suggest that the dosage of E2A, HEB, and SCL determines pTalpha gene expression in immature T cells.

* This work was supported by grants from the Canadian Institute for Health Research (CIHR) and the National Cancer Institute of Canada (NCIC) with funds from the Canadian Cancer Society.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by a studentship from the Fonds de recherche sur la nature et les technologies.

Recipient of a postdoctoral fellowship from the Leukemia Research Fund.

|| Recipient of a studentship from CIHR.

Dagger Dagger To whom correspondence should be addressed: Institut de Recherches Cliniques de Montréal, 110, avenue des Pins Ouest, Montréal, Québec H2W 1R7, Canada. Tel.: 514-987-5588; Fax: 514-987-5757; E-mail: hoangt@ircm.qc.ca.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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