Stegmann Anders, Hansen Morten, Wang Yulan, Larsen Janus B, Lund Leif R, Ritié Léa, Nicholson Jeremy K, Quistorff Bjørn, Simon-Assmann Patricia, Troelsen Jesper T, Olsen Jørgen
Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Physiol Genomics. 2006 Oct 11;27(2):141-55. doi: 10.1152/physiolgenomics.00314.2005. Epub 2006 Jul 25.
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 (1)H 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).
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。在本研究中，我们采用生物信息学方法来寻找在小肠上皮细胞分化过程中可能作为基因调控网络节点发挥作用的转录因子。此外，我们还寻找了转录因子与绒毛代谢组之间的联系。转录组数据来自小鼠小肠绒毛、隐窝和胎儿肠上皮细胞。代谢组数据来自隐窝和绒毛细胞。我们的结果表明，在从胎儿到成年以及从隐窝到绒毛的分化过程中上调的基因，其启动子中潜在的肝细胞核因子（HNF）-4结合位点过度富集。此外，通过魔角旋转（1）H核磁共振光谱进行的代谢组分析表明，绒毛上皮细胞中脂质碳链的浓度高于隐窝细胞。这些发现提示了一种模型，即HNF-4转录因子通过调控参与脂质代谢的基因来影响绒毛代谢组。我们的方法还鉴定出了对隐窝功能（如DNA复制（E2F）和干细胞维持（c-Myc））重要的转录因子。
