Unknown,Transcriptomics,Genomics,Proteomics

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Quantitative transcriptome analysis of a high-GSH producing Saccharomyces cerevisiae and the wild type based on the second generation sequencing.

ABSTRACT: The mutant Saccharomyces cerevisiae Y518 generated much more intracellular glutathione (GSH) than its counterpart dose. The RNA-seq based global transcriptome analysis was performed for exploring the potential mechanisms. Statistical analysis indicated that 1125 differentially expressed genes (fold-change>=2.0, FDR<=0.001) were up-regulated and 503 were down-regulated. There were 12 genes involved in glutathione metabolism. Of which GSH1, encodes gamma-glutamine cysteine synthetase, the rate-limiting enzyme in GSH biosynthesis process, was up-regulated. And MET17, encodes cysteine synthase A, an enzyme catalyzes the biosynthesis of one of the precursor amino acids L- cysteine, was also up-regulated. Besides, regulator SKN7 and several genes involved in oxidative stress response (GPX2, CTT1, SOD1, TRX2) were up-regulated. Intracellular ROS level of Y518 was also enhanced compared to that of 2-10515. Our results indicate that up-regulations of GSH1 and MET17 might be associated with the increased intracellular GSH content of the mutant, and up-regulated GSH1 may be caused by increased intracellular ROS level. Saccharomyces cerevisiae mRNA profiles of 24-h wild type 2-10515 and mutant Y518 were generated by deep sequencing using Illumina HiSeqTM 2000

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Jiang Sun

PROVIDER: E-GEOD-47787 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Glutathione (GSH) is a critical endogenous antioxidant that protects against intracellular oxidative stress. As such, pathological alterations in GSH levels are linked to a myriad of diseases including cancer, neurodegeneration and cataract. The rate limiting step in GSH biosynthesis is catalyzed by the glutamate cysteine ligase catalytic subunit (GCLC). The high expression of GCLC in the lens supports the synthesis of millimolar concentrations of GSH in this tissue. Herein, we describe the morphological consequences of deleting (knocking out) Gclc from surface ectoderm-derived ocular tissues (using the Le-Cre transgene; Gclc KO) which includes an overt microphthalmia phenotype and severely disrupted formation of multiple ocular structures (i.e., cornea, iris, lens, retina). Controlling for the Le-Cre transgene revealed that the deletion of Gclc significantly exacerbated the microphthalmia phenotype in Le-Cre hemizygous mice and resulted in dysregulated gene expression that was unique to only the lenses of KO mice. We further characterized the impaired lens development by conducting an RNA-seq experiment on KO and Gclc control (CON) mouse lens at the day of birth. RNA-sequencing revealed significant differences between Gclc knockout (KO) and Gclc control (CON) lenses, including down-regulation of crystallins and lens fiber cell identity genes, and up-regulation of lens epithelial cell identity genes. In addition, genes related to the immune system (e.g., immune system process, inflammatory response, neutrophil chemotaxis) were upregulated, and genes related to eye/lens development were downregulated. TRANSFAC analysis of differentially expressed genes (DEGs) in the lens of Gclc KO mice implicated PAX6 as a key upstream regulator of Gclc KO sensitive genes. This was further supported by a strong positive correlation between the transcriptomes of the lenses of Gclc KO and Pax6 KO mice. Strikingly, the dysregulation of PAX6-regulated genes in Gclc KO mice was observed despite no change in the ocular localization of PAX6 or decrease in the expression of PAX6 in the lens. In vitro experiments demonstrated that suppression of intracellular GSH concentrations resulted in impairment of PAX6 transactivation activity. Taken together, the present results elucidate a novel mechanism wherein intracellular GSH concentrations may modulate PAX6 activity.

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Quantitative transcriptome analysis of a high-GSH producing Saccharomyces cerevisiae and the wild type based on the second generation sequencing.

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