Wu Chang-Yi, Bird Amanda J, Chung Lisa M, Newton Michael A, Winge Dennis R, Eide David J
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
BMC Genomics. 2008 Aug 1;9:370. doi: 10.1186/1471-2164-9-370.
The Zap1 transcription factor is a central player in the response of yeast to changes in zinc status. We previously used transcriptome profiling with DNA microarrays to identify 46 potential Zap1 target genes in the yeast genome. In this new study, we used complementary methods to identify additional Zap1 target genes.
With alternative growth conditions for the microarray experiments and a more sensitive motif identification algorithm, we identified 31 new potential targets of Zap1 activation. Moreover, an analysis of the response of Zap1 target genes to a range of zinc concentrations and to zinc withdrawal over time demonstrated that these genes respond differently to zinc deficiency. Some genes are induced under mild zinc deficiency and act as a first line of defense against this stress. First-line defense genes serve to maintain zinc homeostasis by increasing zinc uptake, and by mobilizing and conserving intracellular zinc pools. Other genes respond only to severe zinc limitation and act as a second line of defense. These second-line defense genes allow cells to adapt to conditions of zinc deficiency and include genes involved in maintaining secretory pathway and cell wall function, and stress responses.
We have identified several new targets of Zap1-mediated regulation. Furthermore, our results indicate that through the differential regulation of its target genes, Zap1 prioritizes mechanisms of zinc homeostasis and adaptive responses to zinc deficiency.
Zap1转录因子在酵母对锌状态变化的反应中起核心作用。我们之前使用DNA微阵列进行转录组分析，以鉴定酵母基因组中的46个潜在Zap1靶基因。在这项新研究中，我们使用互补方法来鉴定更多的Zap1靶基因。
通过微阵列实验的替代生长条件和更灵敏的基序识别算法，我们鉴定出31个新的潜在Zap1激活靶标。此外，对Zap1靶基因对一系列锌浓度和随时间的锌去除的反应分析表明，这些基因对锌缺乏的反应不同。一些基因在轻度锌缺乏时被诱导，并作为抵御这种应激的第一道防线。一线防御基因通过增加锌摄取以及动员和保存细胞内锌库来维持锌稳态。其他基因仅对严重的锌限制作出反应，并作为第二道防线。这些二线防御基因使细胞能够适应锌缺乏的条件，包括参与维持分泌途径和细胞壁功能以及应激反应的基因。
我们鉴定出了几个新的Zap1介导调控的靶标。此外，我们的结果表明，通过对其靶基因的差异调控，Zap1对锌稳态机制和对锌缺乏的适应性反应进行了优先级排序。
