Godard Patrice, Urrestarazu Antonio, Vissers Stéphan, Kontos Kevin, Bontempi Gianluca, van Helden Jacques, André Bruno
Physiologie Moléculaire de la Cellule, IBMM, Université Libre de Bruxelles, Rue des Pr. Jeener et Brachet 12, 6041 Gosselies, Belgium.
Mol Cell Biol. 2007 Apr;27(8):3065-86. doi: 10.1128/MCB.01084-06. Epub 2007 Feb 16.
We compared the transcriptomes of Saccharomyces cerevisiae cells growing under steady-state conditions on 21 unique sources of nitrogen. We found 506 genes differentially regulated by nitrogen and estimated the activation degrees of all identified nitrogen-responding transcriptional controls according to the nitrogen source. One main group of nitrogenous compounds supports fast growth and a highly active nitrogen catabolite repression (NCR) control. Catabolism of these compounds typically yields carbon derivatives directly assimilable by a cell's metabolism. Another group of nitrogen compounds supports slower growth, is associated with excretion by cells of nonmetabolizable carbon compounds such as fusel oils, and is characterized by activation of the general control of amino acid biosynthesis (GAAC). Furthermore, NCR and GAAC appear interlinked, since expression of the GCN4 gene encoding the transcription factor that mediates GAAC is subject to NCR. We also observed that several transcriptional-regulation systems are active under a wider range of nitrogen supply conditions than anticipated. Other transcriptional-regulation systems acting on genes not involved in nitrogen metabolism, e.g., the pleiotropic-drug resistance and the unfolded-protein response systems, also respond to nitrogen. We have completed the lists of target genes of several nitrogen-sensitive regulons and have used sequence comparison tools to propose functions for about 20 orphan genes. Similar studies conducted for other nutrients should provide a more complete view of alternative metabolic pathways in yeast and contribute to the attribution of functions to many other orphan genes.
我们比较了酿酒酵母细胞在稳态条件下利用21种独特氮源生长时的转录组。我们发现有506个基因受氮的差异调节，并根据氮源估计了所有已鉴定的氮响应转录调控的激活程度。一类主要的含氮化合物支持快速生长和高度活跃的氮分解代谢物阻遏（NCR）调控。这些化合物的分解代谢通常产生可被细胞代谢直接同化的碳衍生物。另一类氮化合物支持较慢的生长，与细胞排泄不可代谢的碳化合物（如杂醇油）有关，其特征是氨基酸生物合成的一般调控（GAAC）被激活。此外，NCR和GAAC似乎相互关联，因为介导GAAC的转录因子GCN4基因的表达受NCR的影响。我们还观察到，几种转录调控系统在比预期更广泛的氮供应条件下是活跃的。作用于不参与氮代谢的基因的其他转录调控系统，如多药耐药性和未折叠蛋白反应系统，也对氮作出反应。我们已经完成了几个氮敏感调节子的靶基因列表，并使用序列比较工具为大约20个孤儿基因提出了功能。对其他营养物质进行类似的研究应该能更全面地了解酵母中的替代代谢途径，并有助于为许多其他孤儿基因赋予功能。
