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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Restriction of apolipoprotein A-IV gene expression to the intestine villus depends on a hormone-responsive element and parallels differential expression of the hepatic nuclear factor 4alpha and gamma isoforms.

The apoA-I/C-III/A-IV gene cluster, like most intestine-specific genes, displays a specific pattern of expression along the intestinal cephalocaudal and crypt-to-villus axes. We have shown that this specific pattern of expression requires the distal apoA-IV promoter and the apoC-III enhancer. Using a new set of transgenic mice, we demonstrate here that the restriction of apoA-IV gene transcription to villus enterocytes requires a hormone-responsive element (HRE) located within the apoA-IV distal promoter. We showed, using nuclear extracts from villus or crypt epithelial cells, that this HRE bound the transcription factor hepatic nuclear factor 4 (HNF-4). We also found that the HNF-4gamma isoform was produced only in the villus, whereas the HNF-4alpha isoform was produced along the entire length of the crypt-to-villus axis. Our results demonstrate that the HRE of the distal apoA-IV promoter is responsible for the restriction of gene expression to villus epithelial cells and that this HRE binds HNF-4 isoforms. The in vivo observation of parallel gradients for apoA-IV and HNF-4gamma gene expression raises questions concerning whether this transcription factor plays a specific role in the control of enterocyte differentiation.[1]

References

  1. Restriction of apolipoprotein A-IV gene expression to the intestine villus depends on a hormone-responsive element and parallels differential expression of the hepatic nuclear factor 4alpha and gamma isoforms. Sauvaget, D., Chauffeton, V., Citadelle, D., Chatelet, F.P., Cywiner-Golenzer, C., Chambaz, J., Pinçon-Raymond, M., Cardot, P., Le Beyec, J., Ribeiro, A. J. Biol. Chem. (2002) [Pubmed]
 
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