C/EBP and Cdx family factors regulate liver fatty acid binding protein transgene expression in the small intestinal epithelium
| Autor: | Lora J. Staloch, Joyce K. Divine, Joshua T. Witten, Theodore C. Simon |
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| Rok vydání: | 2005 |
| Předmět: |
Transcription
Genetic Transgene Crypt Biophysics Biology Fatty Acid-Binding Proteins digestive system Biochemistry Intestinal mucosa Structural Biology Gene expression Genetics Transcriptional regulation Animals Humans Transgenes Binding site Intestinal Mucosa Promoter Regions Genetic Regulation of gene expression Homeodomain Proteins Binding Sites Ccaat-enhancer-binding proteins digestive oral and skin physiology Molecular biology Immunohistochemistry Rats Gene Expression Regulation Mutagenesis Hepatocyte Nuclear Factor 1 CCAAT-Enhancer-Binding Proteins Caco-2 Cells HeLa Cells |
| Zdroj: | Biochimica et biophysica acta. 1731(3) |
| ISSN: | 0006-3002 |
| Popis: | 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/EBPalpha, and C/EBPbeta 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-1alpha but not HNF-1beta to activate the transgene. Furthermore, CDX-1, CDX-2, C/EBPalpha, and C/EBPbeta bound to HNF-1alpha and HNF-1beta. 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. |
| Databáze: | OpenAIRE |
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