Molecular Cancer Research, University Medical Centre Utrecht, Utrecht, the Netherlands.
BMC Genomics. 2012 Jun 14;13:239. doi: 10.1186/1471-2164-13-239.
Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays.
In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system.
The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.
细胞内葡萄糖的供应对大多数生物过程的运作至关重要。通过研究模式生物酿酒酵母，我们对葡萄糖调节系统有了更深入的了解，但该系统的许多方面仍不明确。为了了解葡萄糖调节系统的组织方式，我们使用 DNA 微阵列分析了酿酒酵母中不同葡萄糖信号和代谢途径的 91 个缺失突变体。
一般来说，这些突变不会引起特定途径的转录反应。相反，我们可以辨别出一种主要的转录反应，其方向变化模拟了高或低糖反应。详细的分析揭示了个体途径及其成员内部和之间的既定和新的关系。与信号成分相比，葡萄糖调节系统的代谢成分在转录上更频繁地受到影响。我们应用了一种新的网络方法来揭示葡萄糖调节系统的层次组织。
不同葡萄糖调节途径之间的紧密联系反映在观察到的主要转录反应中。参与储存性碳水化合物海藻糖生物合成的两种酶 Tps2 和 Tsl1 被预测为最下游的转录成分。tps2Δ 双突变体的上位性分析支持了这一预测。尽管这些结果仅基于转录变化，但它们表明所有感知葡萄糖水平的变化最终都会导致海藻糖生物合成的转变。
