Ao Wanyuan, Gaudet Jeb, Kent W James, Muttumu Srikanth, Mango Susan E
Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Science. 2004 Sep 17;305(5691):1743-6. doi: 10.1126/science.1102216.
Growth and development of the Caenorhabditis elegans foregut (pharynx) depends on coordinated gene expression, mediated by pharynx defective (PHA)-4/FoxA in combination with additional, largely unidentified transcription factors. Here, we used whole genome analysis to establish clusters of genes expressed in different pharyngeal cell types. We created an expectation maximization algorithm to identify cis-regulatory elements that activate expression within the pharyngeal gene clusters. One of these elements mediates the response to environmental conditions within pharyngeal muscles and is recognized by the nuclear hormone receptor (NHR) DAF-12. Our data suggest that PHA-4 and DAF-12 endow the pharynx with transcriptional plasticity to respond to diverse developmental and physiological cues. Our combination of bioinformatics and in vivo analysis has provided a powerful means for genome-wide investigation of transcriptional control.
秀丽隐杆线虫前肠(咽)的生长和发育依赖于由咽缺陷(PHA)-4/FoxA与其他大量未鉴定的转录因子共同介导的协调基因表达。在此,我们利用全基因组分析来建立在不同咽细胞类型中表达的基因簇。我们创建了一种期望最大化算法,以识别激活咽基因簇内表达的顺式调控元件。其中一个元件介导咽肌对环境条件的反应,并被核激素受体(NHR)DAF-12识别。我们的数据表明,PHA-4和DAF-12赋予咽转录可塑性,以响应多种发育和生理信号。我们将生物信息学与体内分析相结合,为全基因组转录调控研究提供了一种强大的方法。