Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, USA.
G3 (Bethesda). 2012 Sep;2(9):1003-17. doi: 10.1534/g3.112.002808. Epub 2012 Sep 1.
Saccharomyces cerevisiae are able to control growth in response to changes in nutrient availability. The limitation for single macronutrients, including nitrogen (N) and phosphate (P), produces stable arrest in G1/G0. Restoration of the limiting nutrient quickly restores growth. It has been shown that glucose (G) depletion/repletion very rapidly alters the levels of more than 2000 transcripts by at least 2-fold, a large portion of which are involved with either protein production in growth or stress responses in starvation. Although the signals generated by G, N, and P are thought to be quite distinct, we tested the hypothesis that depletion and repletion of any of these three nutrients would affect a common core set of genes as part of a generalized response to conditions that promote growth and quiescence. We found that the response to depletion of G, N, or P produced similar quiescent states with largely similar transcriptomes. As we predicted, repletion of each of the nutrients G, N, or P induced a large (501) common core set of genes and repressed a large (616) common gene set. Each nutrient also produced nutrient-specific transcript changes. The transcriptional responses to each of the three nutrients depended on cAMP and, to a lesser extent, the TOR pathway. All three nutrients stimulated cAMP production within minutes of repletion, and artificially increasing cAMP levels was sufficient to replicate much of the core transcriptional response. The recently identified transceptors Gap1, Mep1, Mep2, and Mep3, as well as Pho84, all played some role in the core transcriptional responses to N or P. As expected, we found some evidence of cross talk between nutrient signals, yet each nutrient sends distinct signals.
酿酒酵母能够根据营养物质可用性的变化来控制生长。包括氮（N）和磷（P）在内的单一营养物质的限制会导致 G1/G0 期的稳定停滞。限制营养物质的恢复会迅速恢复生长。研究表明，葡萄糖（G）的耗尽/补充会非常迅速地改变 2000 多个转录物的水平，其中至少有一部分与生长过程中的蛋白质产生或饥饿时的应激反应有关。尽管 G、N 和 P 产生的信号被认为是截然不同的，但我们测试了这样一个假设，即这三种营养物质中的任何一种的耗尽和补充都会影响一组共同的核心基因，作为促进生长和静止状态的通用反应的一部分。我们发现，G、N 或 P 的耗尽会产生类似的静止状态，转录组也有很大的相似性。正如我们所预测的，G、N 或 P 中任何一种营养物质的补充都会诱导一个大的（501 个）共同核心基因集，并抑制一个大的（616 个）共同基因集。每种营养物质也会产生特定于营养物质的转录变化。对这三种营养物质的转录反应都依赖于 cAMP，在较小程度上依赖于 TOR 途径。在补充后的几分钟内，这三种营养物质都会刺激 cAMP 的产生，而人为地增加 cAMP 水平足以复制大部分核心转录反应。最近发现的跨受体 Gap1、Mep1、Mep2 和 Mep3 以及 Pho84 在对 N 或 P 的核心转录反应中都发挥了一定的作用。正如预期的那样，我们发现了一些营养信号之间相互作用的证据，但每种营养物质都发出了不同的信号。
