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Originally published In Press as doi:10.1074/jbc.M102002200 on June 6, 2001

J. Biol. Chem., Vol. 276, Issue 34, 32122-32128, August 24, 2001
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Sucrase-isomaltase Gene Transcription Requires the Hepatocyte Nuclear Factor-1 (HNF-1) Regulatory Element and Is Regulated by the Ratio of HNF-1alpha to HNF-1beta *

François BoudreauDagger , Yi Zhu, and Peter G. Traber§

From the Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

The mouse sucrase-isomaltase (SI) gene is an enterocyte-specific gene expressed in a complex developmental pattern. We previously reported that a short, evolutionarily conserved gene promoter regulates developmental expression of SI in mouse small intestine. Herein, we investigated the role of a hepatocyte nuclear factor-1 (HNF-1) cis-acting element to regulate SI gene expression in vivo. Transgenic SI gene constructs with a mutated HNF-1 element (SIF3) revealed a strong reduction in promoter activity in comparison with a wild-type construct in mice and during Caco-2 cell differentiation. Nuclear proteins isolated from enterocytes showed increased binding of the HNF-1alpha complex with a concomitant decrease in the HNF-1beta -containing complex to the SIF3 element both during the suckling-weaning developmental transition and Caco-2 cell differentiation. These changes coincided with a strong induction of SI gene transcription. In transfection experiments, HNF-1alpha activated the SI promoter via the SIF3 element, and co-expression of HNF-1beta impaired this transcriptional activation. These findings demonstrate the essential role of the HNF-1 regulatory element to support SI gene transcription in vivo and suggest that the ratio of HNF-1alpha to HNF-1beta plays a role in the transcriptional activity of this gene during intestinal development.


* 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.This

work was supported by RO1-DK46704 (to P.G.T.) and the Molecular Biology Core of the Center for Molecular Studies in Digestive Diseases at the University of Pennsylvania (P30-DK50306).

Dagger Supported by a postdoctoral fellowship from the "Fonds de la Recherche en Santé du Québec."

§ To whom correspondence should be addressed: 709 Swedeland Rd., P.O. Box 1539, King of Prussia, PA 19406-0939. Tel.: 610-270-6016; Fax: 610-270-6116; E-mail: Peter_G_Traber@sbphrd.com.


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


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