Figure 6

Global model of the arsenic response: combining phenotypic data with gene-expression profiles reveals synergistic pathways leading to yeast detoxification mechanisms. Serine, threonine, aspartate and arginine, as well as shikimate metabolisms, in light blue, represent pathways that are judged as sensitive by phenotypic profiling. Yap1, colored light blue and red, is an example of a transcription factor that is both sensitive and confers induced gene expression. Deletion analysis confirms its role in arsenic-mediated control of the stress response. Red and green represent pathways or genes that are differentially expressed but not sensitive by phenotypic profiling. This schematic diagram demonstrates how the deletion of an individual gene leads to a change in sensitivity if the protein product of that gene is important in a biological process for adaptation to arsenic. On the other hand, expression profiling shows the end product of the cell's response to arsenic. Many of these downstream targets share redundant functions and are not vulnerable in the phenotypic profiling. The expression changes lead to the cell's response to indirect oxidative stress and mechanisms for detoxification. The arrows A, B, C and D represent the multiple branchpoints between redundant pathways. Note that the transport protein, Arr3, which extrudes AsIII out of the cell, is both sensitive and highly differentially expressed.