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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
Regulation of pT Gene Expression by a Dosage
of E2A, HEB, and SCL*
Mathieu
Tremblay §,
Sabine
Herblot ¶,
Eric
Lécuyer , and
Trang
Hoang **
From the 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 pT
gene is required for effective selection, proliferation, and survival
of T-cell receptor ( TCR)-expressing immature thymocytes.
Here, we have identified two phylogenetically conserved E-boxes within
the pT 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 pT as a direct target of E2A-HEB heterodimers in immature thymocytes because they specifically occupy the enhancer in vivo. In these cells, pT 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 pT is up-regulated. Taken together, our observations
suggest that the dosage of E2A, HEB, and SCL determines pT 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.

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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