Mapping of HNF4 binding sites, acetylation of histone H3 and expression in Caco2 cells

Background & Aims: The role of HNF4 has been extensively studied in hepatocytes and pancreatic cells, but emerging evidence indicates that HNF4 is a key regulator of intestinal epithelial cell differentiation as well. The aim of the present work is to identify HNF4 target genes in the intestine in order to elucidate the role of HNF4 in differentiation of the intestinal epithelial cells. Results: One thousand one hundred and seventy-six genes were identified as HNF4 targets, many of which have not previously been described as being regulated by HNF4. The 1,176 genes contributed significantly to gene ontology (GO) pathways categorized by lipid and amino acid transport and metabolism. A thorough analysis of Cdx-2, trehalase, and cingulin promoters verified that these genes are regulated by HNF4. In each case we were able to identify a functional HNF4 binding site in their promoters. Conclusions: HNF4 regulation of the Cdx-2 promoter unravels a transcription factor network also including HNF1 and , all of which are transcription factors involved in intestinal development and gene expression.

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