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.
Sauvaget
Dominique
D
U505 INSERM, Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Chauffeton
Valérie
V
Citadelle
Danièle
D
Chatelet
François-Patrick
FP
Cywiner-Golenzer
Charlotte
C
Chambaz
Jean
J
Pinçon-Raymond
Martine
M
Cardot
Philippe
P
Le Beyec
Johanne
J
Ribeiro
Agnès
A
D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019556:COS Cells; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D020895:Enterocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D051557:Hepatocyte Nuclear Factor 4; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics*
D001054:Apolipoproteins A; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; C501970:Tcfl4 protein, mouse; D014157:Transcription Factors; C022205:apolipoprotein A-IV