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Nucleic Acids Research, 2002, Vol. 30, No. 13 2736-2741
© 2002 Oxford University Press

Opposing effects of Krüppel-like factor 4 (gut-enriched Krüppel-like factor) and Krüppel-like factor 5 (intestinal-enriched Krüppel-like factor) on the promoter of the Krüppel-like factor 4 gene

Duyen T. Dang, Weidong Zhao1, Channing S. Mahatan, Deborah E. Geiman and Vincent W. Yang1,2,*

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, 1 Division of Digestive Diseases, Department of Medicine and 2 Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA

KLF4 (Krüppel-like factor 4 or gut-enriched Krüppel-like factor, GKLF) and KLF5 (Krüppel-like factor 5 or intestinal-enriched Krüppel-like factor, IKLF) are two closely related members of the zinc finger-containing Krüppel-like factor family of transcription factors. Although both genes are expressed in the intestinal epithelium, their distributions are different: Klf4 is primarily expressed in the terminally differentiated villus cells while Klf5 is primarily in the proliferating crypt cells. Previous studies show that Klf4 is a negative regulator of cell proliferation and Klf5 is a positive regulator of cell proliferation. In this study, we demonstrate that Klf5 binds to a number of cis-DNA elements that have previously been shown to bind to Klf4. However, while Klf4 activates the promoter of its own gene, Klf5 suppresses the Klf4 promoter. Moreover, Klf5 abrogates the activating effect of Klf4 on the Klf4 promoter and Klf4 abrogates the inhibitory effect of Klf5 on the same promoter. An explanation of this competing effect is due to physical competition of the two proteins for binding to cognate DNA sequence. The complementary tissue localization of expression of Klf4 and Klf5 and the opposing effect of the two Klfs on the Klf4 promoter activity may provide a basis for the coordinated regulation of expression of the Klf4 gene in the intestinal epithelium.

* To whom correspondence should be addressed at: Emory University School of Medicine, Department of Medicine, Division of Digestive Diseases, 201 Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA 30322, USA. Tel: +1 404 7275638; Fax: +1 404 727 5767; Email: vyang@emory.edu


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