Regulation of signaling genes by TGFbeta during entry into dauer diapause in C. elegans

BACKGROUND: When resources are scant, C. elegans larvae arrest as long-lived dauers under the control of insulin/IGF- and TGFbeta-related signaling pathways. : We have identified genes that show different levels of expression in a comparison of wild-type L2 or L3 larvae (non-dauer) to TGFbeta mutants at similar developmental stages undergoing dauer formation. Many insulin/IGF pathway and other known dauer regulatory genes have changes in expression that suggest strong positive feedback by the TGFbeta pathway. In addition, many insulin-like ligand and novel genes with similarity to the extracellular domain of insulin/IGF receptors have altered expression. We have identified a large group of regulated genes with putative binding sites for the FOXO transcription factor, DAF-16. Genes with DAF-16 sites upstream of the transcription start site tend to be upregulated, whereas genes with DAF-16 sites downstream of the coding region tend to be downregulated. Finally, we also see strong regulation of many novel hedgehog- and patched-related genes, hormone biosynthetic genes, cell cycle genes, and other regulatory genes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Computed

背景：当资源匮乏时，秀丽隐杆线虫（C. elegans）幼虫会发育停滞为长寿的持久态幼虫（dauer），该过程受胰岛素/胰岛素样生长因子（insulin/IGF）与转化生长因子β（TGFβ）相关信号通路的调控。本研究对比了处于相似发育阶段、正处于持久态形成过程中的转化生长因子β突变体与野生型L2期或L3期非持久态幼虫的基因表达谱，筛选得到了表达水平存在差异的基因。诸多胰岛素/胰岛素样生长因子通路基因及其他已知的持久态调控基因，其表达变化提示转化生长因子β通路存在显著的正反馈调控作用。此外，大量胰岛素样配体及与胰岛素/胰岛素样生长因子受体胞外结构域具有同源性的新型基因，其表达也发生了改变。本研究还筛选得到一大组受调控的基因，这些基因均带有叉头框O（FOXO）转录因子DAF-16的潜在结合位点。在转录起始位点上游带有DAF-16结合位点的基因通常表达上调，而在编码区下游带有DAF-16结合位点的基因则往往表达下调。最后，本研究还观察到大量新型刺猬（hedgehog）与patched相关基因、激素生物合成基因、细胞周期基因及其他调控基因均受到显著调控。本数据集为按共享生物学背景（如物种、肿瘤类型、生物学过程等）分组的基因芯片集。关键词：逻辑集（Logical Set）、计算型（Computed）