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Haugen AC, et al.  (2004) Integrating phenotypic and expression profiles to map arsenic-response networks. Genome Biol 5(12):R95

Abstract: BACKGROUND: Arsenic is a nonmutagenic carcinogen affecting millions of people. The cellular impact of this metalloid in Saccharomyces cerevisiae was determined by profiling global gene expression and sensitivity phenotypes. These data were then mapped to a metabolic network composed of all known biochemical reactions in yeast, as well as the yeast network of 20,985 protein-protein/protein-DNA interactions. RESULTS: While the expression data unveiled no significant nodes in the metabolic network, the regulatory network revealed several important nodes as centers of arsenic-induced activity. The highest-scoring proteins included Fhl1, Msn2, Msn4, Yap1, Cad1 (Yap2), Pre1, Hsf1 and Met31. Contrary to the gene-expression analyses, the phenotypic-profiling data mapped to the metabolic network. The two significant metabolic networks unveiled were shikimate, and serine, threonine and glutamate biosynthesis. We also carried out transcriptional profiling of specific deletion strains, confirming that the transcription factors Yap1, Arr1 (Yap8), and Rpn4 strongly mediate the cell's adaptation to arsenic-induced stress but that Cad1 has negligible impact. CONCLUSIONS: By integrating phenotypic and transcriptional profiling and mapping the data onto the metabolic and regulatory networks, we have shown that arsenic is likely to channel sulfur into glutathione for detoxification, leads to indirect oxidative stress by depleting glutathione pools, and alters protein turnover via arsenation of sulfhydryl groups on proteins. Furthermore, we show that phenotypically sensitive pathways are upstream of differentially expressed ones, indicating that transcriptional and phenotypic profiling implicate distinct, but related, pathways.

Status: Published Type: Journal Article PubMed ID: 15575969

Topics addressed in this paper

Number of different genes curated to this paper: 68

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ARG1 ARO1 ARO2 ARO7 ARR1 ARR2 ARR3 ATR1 CAD1 CDC26
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Topics Genes linked to topics (#11 - 20 )
CIN2 CIT2 CPA1 CPA2 DCP1 ERO1 FHL1 FLR1 GLR1 GRE2
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Topics Genes linked to topics (#21 - 30 )
GRX8 GSH1 HCA4 HOM2 HOM3 HOM6 HSF1 MET1 MET10 MET14
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Topics Genes linked to topics (#31 - 40 )
MET16 MET22 MET3 MET31 MET32 MET4 MET5 MET8 MSN2 MSN4
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Topics Genes linked to topics (#41 - 50 )
MUP1 MUP3 OYE3 PRE1 PRE10 PRE4 RAD53 RAD6 RPN2 RPN4
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Topics Genes linked to topics (#51 - 60 )
RPN5 RPN6 RPN8 RPT3 SAM3 SAM4 SER1 SER2 SER3 SUL1
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Topics Genes linked to topics (#61 - 68 )
SUL2 THR4 TRX2 UBC11 UBC4 UBR1 UFO1 YAP1
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