Mapping of HNF4alpha target genes in intestinal epithelial cells.
Mapping of HNF4alpha target genes in intestinal epithelial cells.
复制标题
肠上皮细胞中HNF4Alpha靶基因的映射。
DOI：
10.1186/1471-230x-9-68
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发表时间：
2009-09-17
影响因子：
2.4
通讯作者：
Troelsen JT
中科院分区：
文献类型：
--
作者：
Boyd M;Bressendorff S;Møller J;Olsen J;Troelsen JT
HNF 4 α在肝细胞和胰腺β细胞中的作用已被广泛研究，HNF 4 α也被认为是肠上皮细胞分化的关键调节因子。本研究的目的是在人肠上皮细胞中鉴定新的HNF 4 α靶基因，以阐明HNF 4 α在肠上皮细胞分化过程中的作用。我们对人肠细胞系Caco-2进行了ChIP芯片分析，以在全基因组范围内鉴定HNF 4 α与启动子区域的结合。将HNF 4 α ChIP芯片数据与启动子的基因表达和组蛋白H3乙酰化状态进行匹配，以鉴定HNF 4 α与具有开放染色质结构的活跃转录基因的结合。1，541个基因被鉴定为潜在的HNF 4 α靶基因，其中许多基因以前未被描述为受HNF 4 α调控。这1,541个基因对基因本体（GO）途径（按脂质和氨基酸转运和代谢分类）有重要贡献。同源域转录因子Cdx-2（CDX 2）、海藻糖酶（TREH）和紧密连接蛋白扣带蛋白（CGN）启动子的分析证实，这些基因在Caco 2细胞中与HNF 4 α结合。对于Cdx-2和海藻糖酶启动子，在小鼠小肠上皮中验证了HNF 4 α结合。Cdx-2启动子的HNF 4 α调控揭示了一个转录因子网络，其中也包括HNF 1 α，所有这些转录因子都参与肠道发育和基因表达。
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.