C/EBP and Cdx family factors regulate liver fatty acid binding protein transgene expression in the small intestinal epithelium

Abstract

A transgene constructed from the rat liver fatty acid binding protein gene ( Fabp1) promoter is active in all murine small intestinal crypt and villus epithelial cells. Coincident Cdx and C/EBP transcription factor binding sites were identified spanning Fabp1 nucleotides −90 to −78. CDX-1, CDX-2, C/EBPα, and C/EBPβ activated the Fabp1 transgene in CaCo-2 cells, and mutagenizing the −78 site prevented activation by these factors. CDX but not C/EBP factors bound to the site in vitro, although C/EBP factors competed with CDX factors for transgene activation. The −78 site adjoins an HNF-1 site, and CDX and C/EBP family factors cooperated with HNF-1α but not HNF-1β to activate the transgene. Furthermore, CDX-1, CDX-2, C/EBPα, and C/EBPβ bound to HNF-1α and HNF-1β. The transgene with a mutagenized −78 site was silenced in vivo specifically in small intestinal crypt epithelial cells but remained active in villus cells. These results demonstrate functional interactions between HNF-1, C/EBP, and CDX family factors and suggest that these interactions may contribute to differential transcriptional regulation in the small intestinal crypt and villus compartments.