Mapping of HNF4α target genes in intestinal epithelial cells
Department of Cellular and Molecular Medicine. Panum Institute, Building 6.4. University of Copenhagen. Blegdamsvej 3B 2200 Copenhagen N, Denmark
BMC Gastroenterology 2009, 9:68 doi:10.1186/1471-230X-9-68Published: 17 September 2009
The role of HNF4α has been extensively studied in hepatocytes and pancreatic β-cells, and HNF4α is also regarded as a key regulator of intestinal epithelial cell differentiation. The aim of the present work is to identify novel HNF4α target genes in the human intestinal epithelial cells in order to elucidate the role of HNF4α in the intestinal differentiation progress.
We have performed a ChIP-chip analysis of the human intestinal cell line Caco-2 in order to make a genome-wide identification of HNF4α binding to promoter regions. The HNF4α ChIP-chip data was matched with gene expression and histone H3 acetylation status of the promoters in order to identify HNF4α binding to actively transcribed genes with an open chromatin structure.
1,541 genes were identified as potential HNF4α targets, many of which have not previously been described as being regulated by HNF4α. The 1,541 genes contributed significantly to gene ontology (GO) pathways categorized by lipid and amino acid transport and metabolism. An analysis of the homeodomain transcription factor Cdx-2 (CDX2), the disaccharidase trehalase (TREH), and the tight junction protein cingulin (CGN) promoters verified that these genes are bound by HNF4α in Caco2 cells. For the Cdx-2 and trehalase promoters the HNF4α binding was verified in mouse small intestine epithelium.
The HNF4α regulation of the Cdx-2 promoter unravels a transcription factor network also including HNF1α, all of which are transcription factors involved in intestinal development and gene expression.