Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation
Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation
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DOI：
10.1152/physiolgenomics.00314.2005
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发表时间：
2006-10-11
影响因子：
4.6
通讯作者：
Olsen, Jorgen
中科院分区：
文献类型：
--
作者：
Stegmann, Anders;Hansen, Morten;Olsen, Jorgen
代谢组学、转录组学和生物信息学顺式元件分析表明，HNF-4是肠上皮细胞分化过程中基因表达的中心调节因子。Physiol Genomics 27：141-155，2006.首次发表于2006年7月25日; doi：10.1152/physiolgenomics。00314.2005.- DNA结合转录因子与携带其结合位点的启动子结合。因此，转录因子在基因调控网络中起着节点的作用。在目前的工作中，我们使用了生物信息学的方法来寻找转录因子，可能作为节点的基因调控网络在小肠上皮细胞的分化。此外，我们还研究了转录因子和绒毛代谢组之间的联系。从小鼠小肠绒毛、隐窝和胎儿肠上皮细胞产生转录组数据。代谢组数据来自隐窝和绒毛细胞。我们的研究结果表明，在胎儿到成人和隐窝绒毛分化过程中上调的基因在其启动子中具有潜在的肝细胞核因子（HNF）-4结合位点的过度表达。此外，通过魔角旋转H-1核磁共振波谱的代谢组学分析表明，绒毛上皮细胞比隐窝细胞含有更高浓度的脂质碳链。这些发现表明，HNF-4转录因子通过调节参与脂质代谢的基因来影响绒毛代谢组的模型。我们的方法还鉴定了对隐窝功能重要的转录因子，如DNA复制（E2 F）和干细胞维持（c-Myc）。
Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation. Physiol Genomics 27: 141-155, 2006. First published July 25, 2006; doi:10.1152/physiolgenomics. 00314.2005.-DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning H-1 nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).