Global transcriptome and deletome profiles of yeast exposed to transition metals.
Global transcriptome and deletome profiles of yeast exposed to transition metals.
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DOI：
10.1371/journal.pgen.1000053
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发表时间：
2008-04-25
期刊：
影响因子：
4.5
通讯作者：
Freedman, Jonathan H.
中科院分区：
文献类型：
--
作者：
Jin, Yong Hwan;Dunlap, Paul E.;McBride, Sandra J.;Al-Refai, Hanan;Bushel, Pierre R.;Freedman, Jonathan H.
各种病理与暴露于必需金属和非必需金属和类金属的超生理浓度有关。将金属暴露与人类病理联系起来的分子机制尚未明确。为了解决我们在理解过渡金属分子生物学方面的这些差距，我们研究了IB族(铜、银)、IIB族(锌、镉、汞)、VIA(铬)和VB(砷)元素对酿酒酵母基因组的影响。在暴露于等毒性浓度的金属后，产生了两套全面的金属响应基因组图谱：一套提供与金属暴露相关的转录变化的信息(转录组)，另一套提供关于∼4,700非必需基因的表达与金属暴露敏感性之间关系的信息(缺失组)。大约22%的基因组受到至少一种金属暴露的影响。主成分和聚类分析表明，金属的化学性质是定义表达谱的主要决定因素。此外，细胞可能已经发展出共同或收敛的调节机制来适应金属暴露。转录组和缺失组共有22个基因，但比较两个基因的基因本体论生物学过程发现，金属胁迫适应和解毒类别具有共同的丰富性。对转录组和缺失组的分析确定了几条进化上保守的信号转导途径，这些途径可能参与调节对金属暴露的反应。在这项研究中，我们确定了对必需和非必需金属暴露做出反应的基因和同源信号通路。此外，还确定了在这些金属存在的情况下生存所必需的基因。这些信息将有助于我们理解生物响应金属胁迫的分子机制，并可能有助于理解环境应激与信号转导途径之间的联系。过渡金属的污染对环境和人类健康构成威胁。各种病理与暴露于必需金属和非必需金属和类金属的超生理浓度有关。为了防御金属毒性，复杂的防御机制已经进化出来。虽然许多基因和调控途径已经被识别，但系统水平上的金属暴露的后果还没有被检验。为了更好地确定金属反应的机制，我们研究了锌、镉、汞、铜、银、铬和砷对酿酒酵母基因表达的影响。此外，还确定了∼4,500非必需基因在保护酵母免受金属毒害中的作用。数据分析表明，金属的化学性质是确定其对细胞的生物效应的主要决定因素。此外，细胞可能已经发展出共同或收敛的调节机制来适应金属暴露。几个进化上保守的调节通路被发现与金属暴露、正常新陈代谢和基因表达的破坏有关。这些结果提供了对金属暴露的生物反应和应激反应的全球理解。
A variety of pathologies are associated with exposure to supraphysiological concentrations of essential metals and to non-essential metals and metalloids. The molecular mechanisms linking metal exposure to human pathologies have not been clearly defined. To address these gaps in our understanding of the molecular biology of transition metals, the genomic effects of exposure to Group IB (copper, silver), IIB (zinc, cadmium, mercury), VIA (chromium), and VB (arsenic) elements on the yeast Saccharomyces cerevisiae were examined. Two comprehensive sets of metal-responsive genomic profiles were generated following exposure to equi-toxic concentrations of metal: one that provides information on the transcriptional changes associated with metal exposure (transcriptome), and a second that provides information on the relationship between the expression of ∼4,700 non-essential genes and sensitivity to metal exposure (deletome). Approximately 22% of the genome was affected by exposure to at least one metal. Principal component and cluster analyses suggest that the chemical properties of the metal are major determinants in defining the expression profile. Furthermore, cells may have developed common or convergent regulatory mechanisms to accommodate metal exposure. The transcriptome and deletome had 22 genes in common, however, comparison between Gene Ontology biological processes for the two gene sets revealed that metal stress adaptation and detoxification categories were commonly enriched. Analysis of the transcriptome and deletome identified several evolutionarily conserved, signal transduction pathways that may be involved in regulating the responses to metal exposure. In this study, we identified genes and cognate signaling pathways that respond to exposure to essential and non-essential metals. In addition, genes that are essential for survival in the presence of these metals were identified. This information will contribute to our understanding of the molecular mechanism by which organisms respond to metal stress, and could lead to an understanding of the connection between environmental stress and signal transduction pathways. Environmental and human health threats are posed by contamination from transition metals. A variety of pathologies are associated with exposure to supraphysiological concentrations of essential metals and to non-essential metals and metalloids. To defend against metal toxicity, sophisticated defense mechanisms have evolved. Although many of the genes and regulatory pathways have been identified, the consequence of metal exposure on a systematic level has not been examined. To better define the mechanism involved in the metal response, we examined the effects of zinc, cadmium, mercury, copper, silver, chromium, and arsenic on gene expression in the yeast Saccharomyces cerevisiae. In addition, the roles of ∼4,500 non-essential genes in protecting yeast from metal toxicity were determined. Data analyses suggest that the chemical properties of the metal are major determinants in defining its biological effect on cells. Furthermore, cells may have developed common or convergent regulatory mechanisms to accommodate metal exposure. Several evolutionarily conserved regulatory pathways were identified that link metal exposure, disruption of normal metabolism and gene expression. These results provide a global understanding of the biological responses to metal exposure and the stress response.
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