Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level (INO2 and INO4) on lipid metabolism in yeast.
BACKGROUND
In the yeast Saccharomyces cerevisiae, genes containing UASINO sequences are regulated by the Ino2/Ino4 and Opi1 transcription factors, and this regulation controls lipid biosynthesis. The expression level of INO2 and INO4 genes (INO-level) at different nutrient limited conditions might lead to various responses in yeast lipid metabolism.


METHODS
In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components.


RESULTS
In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components.


CONCLUSIONS
Our analysis showed the strength of using a combination of transcriptome and lipidome analysis to illustrate the effect of INO-levels on phospholipid metabolism and based on our analysis we established a global regulatory map.
Pramote
P
Chumnanpuen
Intawat
I
Nookaew
Jens
J
Nielsen
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002244:Carbon / Q000737:chemistry; D003470:Culture Media; D004952:Esters / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D005285:Fermentation; D005658:Fungi / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D007294:Inositol / Q000737:chemistry; D050356:Lipid Metabolism; D009584:Nitrogen / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
D051792:Basic Helix-Loop-Helix Proteins; D002244:Carbon; D003470:Culture Media; D004952:Esters; D005227:Fatty Acids; D007294:Inositol; D009584:Nitrogen; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C095723:INO2 protein, S cerevisiae; C063311:INO4 protein, S cerevisiae