Raffelsberger Wolfgang, Dembélé Doulaye, Neubauer Mike G, Gottardis Marco M, Gronemeyer Hinrich
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 10142, C. U. de Strasbourg, France.
Genomics. 2002 Oct;80(4):385-94. doi: 10.1006/geno.2002.6848.
Large-scale gene expression profiling with DNA microarrays opens new dimensions to molecular biology but still lacks the overall precision of traditional low-scale techniques. We developed a novel strategy of data processing linking search stringency to quality indicators for efficient detection of low-level, regulated genes. Using retinoid-induced differentiation of NB-4 promyelocytic cells, the variation of expression profiles between biological duplicates was studied and compared with the changes induced by all-trans retinoic acid (atRA) treatment. An analysis of 4320 genes showed that retinoic acid has mainly geneactivating function in NB-4 cells. Treatment with atRA for 18 hours induced metabolic genes that may be associated with cell differentiation and signaling factors triggering later events leading to apoptosis; cytokine genes were among the highest stimulated by atRA. Notably, we identified a regulatory loop inhibiting MYC action: as MYC was downregulated, a cognate repressor of MYC was upregulated.
利用DNA微阵列进行大规模基因表达谱分析为分子生物学开辟了新的维度,但仍缺乏传统小规模技术的整体精度。我们开发了一种新颖的数据处理策略,将搜索严格性与质量指标相联系,以有效检测低水平的调控基因。利用维甲酸诱导NB-4早幼粒细胞分化,研究了生物学重复样本之间表达谱的变化,并与全反式维甲酸(atRA)处理诱导的变化进行了比较。对4320个基因的分析表明,维甲酸在NB-4细胞中主要具有基因激活功能。用atRA处理18小时可诱导可能与细胞分化相关的代谢基因以及触发导致细胞凋亡的后续事件的信号因子;细胞因子基因是受atRA刺激最高的基因之一。值得注意的是,我们发现了一个抑制MYC作用的调控环:随着MYC的下调,MYC的一个同源抑制因子上调。