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 cell-cell adhesion controls the nuclear abundance of the transcription factor hepatic nuclear factor 4alpha, 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 the apoA-IV gene, through the control of hepatic nuclear factor 4alpha nuclear abundance.
Peignon
Gregory
G
Université Pierre et Marie Curie UMRS 505, Paris, F-75006 France, INSERM, UMRS 505, F-75006 Paris, France.
Thenet
Sophie
S
Schreider
Cyrille
C
Fouquet
Stéphane
S
Ribeiro
Agnès
A
Dussaulx
Elizabeth
E
Chambaz
Jean
J
Cardot
Philippe
P
Pinçon-Raymond
Martine
M
Le Beyec
Johanne
J
D001054:Apolipoproteins A / Q000096:biosynthesis* / Q000235:genetics; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D020895:Enterocytes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D001054:Apolipoproteins A; D015820:Cadherins; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D008024:Ligands; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C022205:apolipoprotein A-IV; D049452:Green Fluorescent Proteins; D008156:Luciferases