Bhattacharya Sushila, Horowitz Brent B, Zhang Jingyan, Li Xuhang, Zhang Hefei, Giese Gabrielle E, Holdorf Amy D, Walhout Albertha J M
Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
iScience. 2022 Jun 30;25(8):104688. doi: 10.1016/j.isci.2022.104688. eCollection 2022 Aug 19.
Metabolic perturbations can affect gene expression, for instance to rewire metabolism. While numerous efforts have measured gene expression in response to individual metabolic perturbations, methods that determine all metabolic perturbations that affect the expression for a given gene or set of genes have not been available. Here, we use a gene-centered approach to derive a first-pass metabolic regulatory network for by performing RNAi of more than 1,400 metabolic genes with a set of 19 promoter reporter strains that express a fluorescent protein in the animal's intestine. We find that metabolic perturbations generally increase promoter activity, which contrasts with transcription factor (TF) RNAi, which tends to repress promoter activity. We identify several TFs that modulate promoter activity in response to perturbations of the electron transport chain and explore complex genetic interactions among metabolic pathways. This work provides a blueprint for a systems-level understanding of how metabolism affects gene expression.
代谢扰动可以影响基因表达，例如重新调整代谢。虽然已经有许多研究测量了基因表达对单个代谢扰动的响应，但尚未有方法能够确定影响给定基因或基因集表达的所有代谢扰动。在这里，我们采用以基因为中心的方法，通过对1400多个代谢基因进行RNA干扰，并利用一组在动物肠道中表达荧光蛋白的19种启动子报告菌株，推导出首个针对[具体对象未明确]的首过代谢调控网络。我们发现，代谢扰动通常会增加启动子活性，这与转录因子（TF）RNA干扰相反，后者往往会抑制启动子活性。我们鉴定出了几种响应电子传递链扰动而调节启动子活性的转录因子，并探索了代谢途径之间复杂的基因相互作用。这项工作为系统层面理解代谢如何影响基因表达提供了蓝图。
