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A novel colonic repressor element regulates intestinal gene expression by interacting with Cux/CDP
François Boudreau1, Edmond H H M Rings, Gary P Swain
1Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Molecular and Cellular Biology
|July 9, 2002
Summary
CCAAT displacement protein (CDP) represses sucrase-isomaltase (SI) gene expression in the colon. This discovery identifies Cux/CDP as a key regulator of intestinal gene repression during development.
Area of Science:
- Molecular biology
- Developmental biology
- Genetics
Background:
- Intestinal gene regulation exhibits spatial and temporal control.
- Sucrase-isomaltase (SI) is an enterocyte-specific gene with complex expression patterns.
Purpose of the Study:
- To investigate the mechanisms of colonic repression of the SI gene.
- To identify regulatory elements and transcription factors involved in SI gene repression.
Main Methods:
- Generation of transgenic mice with a mutated SI transgene.
- Analysis of the CRESIP (colon-repressive element of the SI promoter) element.
- Study of Cux/CDP interaction with the SI promoter.
- Phenotypic analysis of Cux/CDP homozygous mutant mice.
Main Results:
- An overlapping CCAAT displacement protein (CDP)-GATA element (CRESIP) mediates SI repression in the colon.
- Cux/CDP interacts with the SI promoter in a CRESIP-dependent manner.
- Cux/CDP homozygous mutant mice show increased SI mRNA expression in early postnatal development.
Conclusions:
- The CRESIP element is crucial for repressing SI expression in the distal gut.
- Cux/CDP acts as a transcriptional repressor of the SI gene during intestinal development.