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Molecular and Cellular Biology, August 2002, p. 5467-5478, Vol. 22, No. 15
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.15.5467-5478.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP

François Boudreau,1 Edmond H. H. M. Rings,1 Gary P. Swain,1 Angus M. Sinclair,2 Eun Ran Suh,1 Debra G. Silberg,1 Richard H. Scheuermann,2 and Peter G. Traber1*

Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104,1 Department of Pathology and Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 753902

Received 7 January 2002/ Returned for modification 11 March 2002/ Accepted 24 April 2002

Intestinal gene regulation involves mechanisms that direct temporal expression along the vertical and horizontal axes of the alimentary tract. Sucrase-isomaltase (SI), the product of an enterocyte-specific gene, exhibits a complex pattern of expression. Generation of transgenic mice with a mutated SI transgene showed involvement of an overlapping CDP (CCAAT displacement protein)-GATA element in colonic repression of SI throughout postnatal intestinal development. We define this element as CRESIP (colon-repressive element of the SI promoter). Cux/CDP interacts with SI and represses SI promoter activity in a CRESIP-dependent manner. Cux/CDP homozygous mutant mice displayed increased expression of SI mRNA during early postnatal development. Our results demonstrate that an intestinal gene can be repressed in the distal gut and identify Cux/CDP as a regulator of this repression during development.

* Corresponding author. Mailing address: 709 Swedeland Rd., P.O. Box 1539, King of Prussia, PA 19406-0939. Phone: (610) 270-6016. Fax: (610) 270-6116. E-mail: Peter_G_Traber{at}gsk.com.

Molecular and Cellular Biology, August 2002, p. 5467-5478, Vol. 22, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.15.5467-5478.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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