Effect of 21 Different Nitrogen Sources on Global Gene Expression in the Yeast Saccharomyces cerevisiae

Abstract

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.

SUPPLEMENTAL MATERIAL

We are grateful to Sanna Venetvaara for her important contribution to the setting up of the microarray experiments in our laboratory and to Nasiha M'Rabet for her help in the carrying out of the first analyses. We are also very grateful to Catherine Jauniaux for her help in the sequencing the NIT1 and SDL1 loci and in the isolation of the gcn2Δ mutant. We also thank all members of the laboratory and the other participants of the ARC project (members of the laboratories of Jacques van Helden, Gianluca Bontempi, and Marcelline Kaufman) for fruitful discussions. Finally, we thank Juergen Stolz for communication of data before publication.

This work was supported by grant FRSM 3.4.605.05.F from the National Funds for Scientific Research, Belgium, grant Bioval 981/3861 (Région Wallonne), and the Communauté Française de Belgique (ARC grant number 04/09-307).