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

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 A-IV (apoA-IV) gene. By impairing or enhancing E-cadherin-dependent cell adhesion, we demonstrate in the present study its involvement in the transcriptional activation of the 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 the apoA-IV promoter. Finally, E- cadherin- dependent cellcell adhesion controls the nuclear abundance of the transcription factor hepatic nuclear factor 4 alpha, which is involved in the enterocytespecific expression of apoA- IV gene. Altogether, our results suggest that E-cadherin controls enterocyte- specific expression of genes, such as the apoA-IV gene, through the control of hepatic nuclear factor 4 alpha nuclear abundance.