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 4α and γ Isoforms

• Published in: The Journal of biological chemistry 2002-09, Vol.277 (37), p.34540-34548
• Main Authors: Sauvaget, Dominique, Chauffeton, Valeárie, Citadelle, Danièle, Chatelet, François-Patrick, Cywiner-Golenzer, Charlotte, Chambaz, Jean, Pinçon-Raymond, Martine, Cardot, Philippe, Le Beyec, Johanne, Ribeiro, Agnès
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M206074200

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-4γ isoform was produced only in the villus, whereas the HNF-4α 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-4γ gene expression raises questions concerning whether this transcription factor plays a specific role in the control of enterocyte differentiation.