Genome-wide functional profiling identifies genes and processes important for zinc-limited growth of Saccharomyces cerevisiae.
Genome-wide functional profiling identifies genes and processes important for zinc-limited growth of Saccharomyces cerevisiae.
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DOI：
10.1371/journal.pgen.1002699
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Eide DJ
中科院分区：
文献类型：
--
作者：
North M;Steffen J;Loguinov AV;Zimmerman GR;Vulpe CD;Eide DJ
Zinc is an essential nutrient because it is a required cofactor for many enzymes and transcription factors. To discover genes and processes in yeast that are required for growth when zinc is limiting, we used genome-wide functional profiling. Mixed pools of ∼4,600 deletion mutants were inoculated into zinc-replete and zinc-limiting media. These cells were grown for several generations, and the prevalence of each mutant in the pool was then determined by microarray analysis. As a result, we identified more than 400 different genes required for optimal growth under zinc-limiting conditions. Among these were several targets of the Zap1 zinc-responsive transcription factor. Their importance is consistent with their up-regulation by Zap1 in low zinc. We also identified genes that implicate Zap1-independent processes as important. These include endoplasmic reticulum function, oxidative stress resistance, vesicular trafficking, peroxisome biogenesis, and chromatin modification. Our studies also indicated the critical role of macroautophagy in low zinc growth. Finally, as a result of our analysis, we discovered a previously unknown role for the ICE2 gene in maintaining ER zinc homeostasis. Thus, functional profiling has provided many new insights into genes and processes that are needed for cells to thrive under the stress of zinc deficiency. Zinc is needed for the growth of all organisms because it acts as a required cofactor for many different proteins. Zinc deficiency is a common problem faced by free-living microbes, as well as plants and animals including humans. Among bacterial and fungal pathogens, zinc deficiency is also a key problem they can encounter during pathogenesis. To identify genes and processes that are important for growth when zinc is scarce, we used genome-wide functional profiling. In this approach, a collection of ∼4,600 mutant yeast strains, each lacking the function of a different gene, was tested to determine which genes are needed for optimal growth in low zinc. More than 400 genes were identified as being important. The identity of these genes implicates a large number of different processes as critical for low zinc growth. These included genes that are targets of the zinc-regulated Zap1 transcription factor as well as genes involved in secretory pathway function, oxidative stress resistance, vesicular trafficking, peroxisome biogenesis, and chromatin modification. As a result, we now know of many processes that might be good targets for the development of new antifungal drugs.
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影响因子：
3.8
作者：
Jo, William J.;Loguinov, Alex;Vulpe, Chris D.
通讯作者：
Vulpe, Chris D.
影响因子：
7.8
作者：
Ellis, Charissa D;Wang, Fudi;MacDiarmid, Colin W;Clark, Suzanne;Lyons, Thomas;Eide, David J
通讯作者：
Eide, David J
影响因子：
4.4
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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