Cox Brian, Kislinger Thomas, Wigle Dennis A, Kannan Anitha, Brown Kevin, Okubo Tadashi, Hogan Brigid, Jurisica Igor, Frey Brendan, Rossant Janet, Emili Andrew
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada.
Mol Syst Biol. 2007;3:109. doi: 10.1038/msb4100151. Epub 2007 May 8.
Although microarray analysis has provided information regarding the dynamics of gene expression during development of the mouse lung, no extensive correlations have been made to the levels of corresponding protein products. Here, we present a global survey of protein expression during mouse lung organogenesis from embryonic day E13.5 until adulthood using gel-free two-dimensional liquid chromatography coupled to shotgun tandem mass spectrometry (MudPIT). Mathematical modeling of the proteomic profiles with parallel DNA microarray data identified large groups of gene products with statistically significant correlation or divergence in coregulation of protein and transcript levels during lung development. We also present an integrative analysis of mRNA and protein expression in Nmyc loss- and gain-of-function mutants. This revealed a set of 90 positively and negatively regulated putative target genes. These targets are evidence that Nmyc is a regulator of genes involved in mRNA processing and a repressor of the imprinted gene Igf2r in the developing lung.
虽然微阵列分析已提供了有关小鼠肺发育过程中基因表达动态的信息,但尚未对相应蛋白质产物的水平进行广泛的相关性研究。在此,我们使用无胶二维液相色谱与鸟枪法串联质谱联用技术(多维蛋白质鉴定技术),对从胚胎第13.5天直至成年的小鼠肺器官发生过程中的蛋白质表达进行了全面调查。对蛋白质组学图谱与平行DNA微阵列数据进行数学建模,确定了在肺发育过程中蛋白质和转录水平的共调控具有统计学显著相关性或差异的大量基因产物组。我们还对Nmyc功能丧失和功能获得突变体中的mRNA和蛋白质表达进行了综合分析。这揭示了一组90个正负调控的假定靶基因。这些靶标证明Nmyc是参与mRNA加工的基因的调节因子,也是发育中的肺中印迹基因Igf2r的抑制因子。