Journal of Biological Chemistry
Volume 277, Issue 48, 29 November 2002, Pages 46544-46551
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GENES: STRUCTURE AND REGULATION
Stra13 Homodimers Repress Transcription through Class B E-box Elements*

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A mammalian basic helix-loop-helix protein known variably as Stra13, Sharp2, and Dec1 has been implicated in cell activation, proliferation, and differentiation. Indeed,Stra13 null mice develop age-induced autoimmunity as a result of impaired T-lymphocyte activation, leading ultimately to the accumulation of autoreactive T-cells and B-cells. Stra13 is expressed in embryonic as well as adult tissues derived from neuroectoderm, mesoderm, and endoderm and has been associated with response to hypoxia, suggesting a complex role for this protein and the highly related Sharp1/Dec2 protein in homeostatic regulation. Whereas Stra13 is known to regulate many important cellular functions and is known to cross-regulate biological responses to other basic helix-loop-helix containing transcription factors, including c-Myc and USF, it is unclear if this protein binds directly to DNA. Indeed, the basic domain of Stra13 contains a proline residue at an unprecedented position. Herein, we have determined that Stra13 binds with high affinity to CACGTG class B E-box elements as a homodimer with preference for elements preceded by T and/or followed by A residues. In addition, transient transfection experiments reveal that Stra13 represses transcription when bound to these and related sites. Our data suggest that Stra13 regulates cellular functions through antagonism of E-box activator proteins and also through active repression from E-box elements.

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This work was supported by a grant from the Canadian Institutes for Health Research (CIHR)/Apotex Inc. and the National Cancer Institute of Canada (to S. E. E.) and a grant from the National Cancer Institute of Canada (to E. Z.).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.

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Present address: Division of Cell and Molecular Biology, Toronto General Research Institute-University Health Network, 67 College St., Toronto, Ontario M5G 2M1, Canada.

Recipient of a CIHR studentship.

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Recipient of a Conseil de la Recherche en Sciences (CRS)/CIHR scholarship.