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A more recent version of this article appeared on February 10, 2006 Originally published In Press as doi:10.1074/jbc.M506360200 on December 7, 2005
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Papers In Press, published online ahead of print January 4, 2006
J. Biol. Chem, 10.1074/jbc.M506360200
Submitted on June 10, 2005
Revised on January 1, 1998
Accepted on December 7, 2005

E-cadherin-dependent transcriptional control of apolipoprotein A-IV gene expression in intestinal epithelial cells: a role for the hepatocyte nuclear factor 4

Gregory Peignon, Sophie Thenet, Cyrille Schreider, Stéphane Fouquet, Agnès Ribeiro, Elizabeth Dussaulx, Jean Chambaz, Philippe Cardot, Martine Pinçon-Raymond, and Johanne Le Beyec

UMR 505 INSERM, Université Pierre et Marie Curie; INSERM; EPHE, Paris 75006

Corresponding Author: jlebihan{at}bhdc.jussieu.fr

Cell-matrix and cell-cell adhesion play a central role in the control of cell proliferation, differentiation and gene expression. Integrins and E-cadherin are the key components involved in these processes in epithelial cells. We recently showed that integrin-dependent adhesion to the extracellular matrix reinforces the formation of E-cadherin-actin complexes inducing the polarization of Caco-2 enterocytes and increases the expression of a marker of enterocyte differentiation, the apolipoprotein (apo) A-IV gene. By impairing or enhancing E-cadherin-dependent cell adhesion, we demonstrate in the present study its involvement in the transcriptional activation of apoA-IV gene in Caco-2 cells. This control requires the regulatory sequence that we have previously identified as necessary and sufficient to drive and restrict apoA-IV gene expression in enterocytes in vivo. Furthermore, using chimeric E-cadherin-Fc homophilic ligand coated surfaces, we show that a direct activation of E-cadherin triggers the transcriptional activation of apoA-IV promoter. Finally, E-cadherin-dependent cell-cell adhesion controls the nuclear abundance of the transcription factor HNF-4a, which is involved in the enterocyte-specific expression of apoA-IV gene. Altogether, our results suggest that E-cadherin controls enterocyte-specific expression of genes, such as apoA-IV gene, through the control of HNF-4a nuclear abundance.


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