Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, Korea.
Nutr Res Pract. 2007 Spring;1(1):19-28. doi: 10.4162/nrp.2007.1.1.19. Epub 2007 Mar 31.
To identify regulatory molecules which play key roles in the development of obesity, we investigated the transcriptional profiles in 3T3-L1 cells at early stage of differentiation and analyzed the promoter sequences of differentially regulated genes. One hundred and sixty-one (161) genes were found to have significant changes in expression at the 2nd day following treatment with differentiation cocktail. Among them, 86 transcripts were up-regulated and 75 transcripts were down-regulated. The 161 transcripts were classified into 10 categories according to their functional roles; cytoskeleton, cell adhesion, immune, defense response, metabolism, protein modification, protein metabolism, regulation of transcription, signal transduction and transporter. To identify transcription factors likely involved in regulating these differentially expressed genes, we analyzed the promoter sequences of up- or -down regulated genes for the presence of transcription factor binding sites (TFBSs). Based on coincidence of regulatory sites, we have identified candidate transcription factors (TFs), which include those previously known to be involved in adipogenesis (CREB, OCT-1 and c-Myc). Among them, c-Myc was also identified by our microarray data. Our approach to take advantage of the resource of the human genome sequences and the results from our microarray experiments should be validated by further studies of promoter occupancy and TF perturbation.
为了鉴定在肥胖发生发展中起关键作用的调控分子,我们在 3T3-L1 细胞分化早期阶段,对其转录组进行了研究,并对差异表达基因的启动子序列进行了分析。在使用分化鸡尾酒处理后的第 2 天,我们发现有 161 个基因的表达发生了显著变化。其中,有 86 个转录本上调,75 个转录本下调。这 161 个转录本根据其功能作用分为 10 类:细胞骨架、细胞黏附、免疫、防御反应、代谢、蛋白质修饰、蛋白质代谢、转录调控、信号转导和转运体。为了鉴定可能参与调控这些差异表达基因的转录因子,我们分析了上调或下调基因的启动子序列中是否存在转录因子结合位点(TFBS)。根据调控位点的一致性,我们确定了候选转录因子(TFs),其中包括先前已知与脂肪生成相关的转录因子(CREB、OCT-1 和 c-Myc)。其中,c-Myc 也被我们的基因芯片数据所鉴定。我们利用人类基因组序列资源的方法和基因芯片实验的结果,应该通过进一步的启动子占据和 TF 干扰研究来验证。