Analysis of transcriptional profiles in Saccharomyces cerevisiae exposed to bisphenol A

We analyzed genome-wide transcriptional profiles of Saccharomyces cerevisiae BY4742 strain in response to BPA, focusing on two exposure scenarios: (i) low-observed-effect concentration (<10% inhibition) to examine chronic effect of BPA on yeast population, and (ii) high-inhibitory concentration (>70% inhibition) to study acute effect. Initially, yeast cells were exposed to various concentrations of BPA. 50 mg/L and 300 mg/L BPA were determined as low-observed-effect concentration and the high-inhibitory concentration, respectively. Transcriptional profiles indicated that 81 genes were repressed and 104 genes were induced in response to 50 mg/L BPA. On the other hand, in 300 mg/L BPA exposure, 378 genes were down-regulated, while 606 genes were significantly up-regulated. Our data showed that there were similar processes affected by both concentrations such as mitochondria, nucleobase-containing small molecule metabolic process, transcription from RNA polymerase II promoter, and mitotic cell cycle and associated processes. However, different modes of actions of the BPA were found between two concentrations. 300 mg/L BPA exposure showed severe effects on the processes by repressing or inducing several genes or total mechanisms with high level of expression changes, while 50 mg/L BPA exposure changed the expression of some important genes with low level of expression changes in the processes. These results suggest that yeast cells respond via different ways to the different concentrations of BPA at transcriptomic level.本研究分析了酿酒酵母（Saccharomyces cerevisiae）BY4742菌株在双酚A（Bisphenol A，BPA）胁迫下的全基因组转录组谱，重点关注两类暴露情境：（i）低观测效应浓度（抑制率<10%），用于探究BPA对酵母群体的慢性影响；（ii）高抑制浓度（抑制率>70%），用于研究其急性效应。实验初始阶段，将酵母细胞暴露于不同浓度的BPA中，最终确定50 mg/L与300 mg/L分别对应低观测效应浓度与高抑制浓度。转录组谱分析结果显示，在50 mg/L BPA暴露条件下，共有81个基因被抑制、104个基因被诱导表达。与之相对，在300 mg/L BPA暴露组中，378个基因表达下调，606个基因显著上调。本研究数据表明，两种浓度的BPA均会影响相似的生物学过程，包括线粒体功能、含核碱基小分子代谢过程、RNA聚合酶II启动子介导的转录以及有丝分裂细胞周期及其相关进程。但两类浓度下BPA的作用模式存在显著差异：300 mg/L BPA暴露通过调控大量基因的表达或整体机制，以较高的表达变化幅度对上述生物学过程造成严重影响；而50 mg/L BPA暴露则仅通过小幅改变部分关键基因的表达，来调控对应生物学进程。上述结果表明，酵母细胞在转录组层面会通过不同的分子机制响应不同浓度的BPA胁迫。