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Originally published In Press as doi:10.1074/jbc.M008277200 on February 6, 2001

J. Biol. Chem., Vol. 276, Issue 18, 14752-14758, May 4, 2001
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POU Homeodomain Protein OCT1 Is Implicated in the Expression of the Caudal-related Homeobox Gene Cdx-2*

Tianru JinDagger § and Huiqin LiDagger

From the Dagger  Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network and the § Department of Medicine and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 2M1, Canada

The caudal homeobox gene Cdx-2 is a transcriptional activator for approximately a dozen genes specifically expressed in pancreatic islets and intestinal cells. It is also involved in preventing the development of colorectal tumors. Studies using "knockout" approaches demonstrated that Cdx-2 is haplo-insufficient in certain tissues including the intestines but not the pancreatic islets. The mechanisms, especially transcription factors, which regulate Cdx-2 expression, are virtually unknown. We found previously that Cdx-2 expression could be autoregulated in a cell type-specific manner. In this study, we located an octamer (OCT) binding site within the mouse Cdx-2 gene promoter. This site, designated as Cdx-2POCT, is involved in the expression of the Cdx-2 promoter. Both pancreatic and intestinal cell lines were found to express a number of POU (OCT binding) homeodomain proteins examined by electrophoretic mobility shift assay. However, it appears that Cdx-2POCT interacts only with OCT1 in the nuclear extracts of the intestinal cell lines examined, although it interacts with OCT1 and at least two other POU proteins that are to be identified in the pancreatic InR1-G9 cell nuclear extract. Co-transfecting OCT1 cDNA but not five other POU gene cDNAs activates the Cdx-2 promoter in the pancreatic InR1-G9 and the intestinal Caco-2 cell lines. In contrast, Cdx-2POCT cannot act as an enhancer element if it is fused to a thymidine kinase promoter. Furthermore, Cdx-2POCT-thymidine kinase fusion promoters cannot be activated by OCT1 co-transfection. Cell type-specific expression, cell type-specific binding affinity of POU proteins to the cis-element Cdx-2POCT, and the DNA content-dependent activation of Cdx-2 promoter via Cdx-2POCT by OCT1 suggest that POU proteins play important and complicated roles in modulating Cdx-2 expression in cell type-specific manners.

* This work is supported by Operating Grant MOP36398 from the Medical Research Council of Canada (to T. J.).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.

To whom correspondence should be addressed: Div. of Cell and Molecular Biology, Toronto General Research Inst. University Health Network, Univ. of Toronto, Rm. 421, 67 College St., Toronto, Ontario, M5G 2M1, Canada. Tel.: 416-340-4800, ext. 4768; Fax: 416-340-3453; E-mail: tianru.jin@utoront.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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