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Intestinal Apolipoprotein A-IV Gene Transcription Is Controlled by Two Hormone-Responsive Elements : A Role for Hepatic Nuclear Factor-4 Isoforms

Archer, Amena (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Sauvaget, Dominique (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Chauffeton, Valérie (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
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Bouchet, Pierre-Etienne (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Chambaz, Jean (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Pinçon-Raymond, Martine (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Cardot, Philippe (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Ribeiro, Agnès (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
Lacasa, Michel (author)
Unité Mixte de Recherche 505, Institut National de la Santé et de la Recherche Médicale-Université Pierre & Marie Curie, 75006 Paris, France
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 (creator_code:org_t)
The Endocrine Society, 2005
2005
English.
In: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 19:9, s. 2320-2334
  • Journal article (peer-reviewed)
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  • In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4α and γ. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4α repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4α and γ functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts.

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