A Stegmann

C Mitchelmore

CR Lussier

D Sauvaget

DG Silberg

DG Taylor

DT Odom

E Soutoglou

E Suh

E van den Akker

EH van Beers

F Beck

F Benahmed

F Boudreau

F Escaffit

F Parviz

G Galand

G Peignon

GD Wu

J Ek

J Olsen

Jesper T Troelsen

Jette Møller

JK Divine

JK Taylor

JP Clatworthy

JT Troelsen

Jørgen Olsen

K Deb

L Wang

M Pinto

M You

ME Torres-Padilla

Mette Boyd

MR Dusing

NF Barley

O Lorentz

PA Gregory

PG Traber

PR Kiela

R Bergoz

R Elkon

R James

RA Irizarry

RC Gentleman

RH Lewinsky

S Citi

S Reddy

SD Krasinski

Simon Bressendorff

SR Frank

T Bosse

T Hinoi

TJ Oesterreicher

W Cairns

WD Garrison

X Gao

YH Hong

English

PubMed

Abstract Background 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. Methods 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. Results 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. Conclusion 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.</p

Olsen Jørgen

Møller Jette

Bressendorff Simon

Boyd Mette

Troelsen Jesper T

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BMC Gastroenterology

Mapping of HNF4α target genes in intestinal epithelial cells

Springer - Publisher Connector

Udgivelsesdato: 2009-Sep-17ABSTRACT: BACKGROUND: The role of HNF4alpha has been extensively studied in hepatocytes and pancreatic beta-cells, and HNF4alpha is also regarded as key regulator of intestinal epithelial cell differentiation as well. The aim of the present work is to identify novel HNF4alpha target genes in the human intestinal epithelial cells in order to elucidate the role of HNF4alpha in the intestinal differentiation progress. METHODS: We have performed a ChIP-chip analysis of the human intestinal cell line Caco-2 in order to make a genome-wide identification of HNF4alpha binding to promoter regions. The HNF4alpha ChIP-chip data was matched with gene expression and histone H3 acetylation status of the promoters in order to identify HNF4alpha binding to actively transcribed genes with an open chromatin structure. RESULTS: 1,541 genes were identified as potential HNF4alpha targets, many of which have not previously been described as being regulated by HNF4alpha. 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 HNF4alpha in Caco2 cells and for the Cdx-2 and trehalase promoters the HNF4alpha binding was verified in mouse small intestine epithelium. CONCLUSION: The HNF4alpha regulation of the Cdx-2 promoter unravels a transcription factor network also including HNF1alpha, all of which are transcription factors involved in intestinal development and gene expression

Boyd, Mette

Bressendorff, Simon

Moller, Jette

Olsen, Jørgen

Troelsen, Jesper

Copenhagen University Research Information System

Mapping of HNF4alpha target genes in intestinal epithelial cells

Crossref

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Mapping of HNF4α target genes in intestinal epithelial cells

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