Transcriptional regulation of phospholipid biosynthesis is linked to fatty acid metabolism by an acyl-CoA-binding-protein-dependent mechanism in Saccharomyces cerevisiae

摘要

pIn the present study, we have used DNA microarray and quantitative real-time PCR analysis to examine the transcriptional changes that occur in response to cellular depletion of the yeast acyl-CoA-binding protein, Acb1p. Depletion of Acb1p resulted in the differential expression of genes encoding proteins involved in fatty acid and phospholipid synthesis (e.g. iFAS1/i, iFAS2/i, iACC1/i, iOLE1/i, iINO1/i and iOPI3/i), glycolysis and glycerol metabolism (e.g. iGPD1/i and iTDH1/i), ion transport and uptake (e.g. iITR1/i and iHNM1/i) and stress response (e.g. iHSP12/i, iDDR2/i and iCTT1/i). In the present study, we show that transcription of the iINO1/i gene, which encodes inositol-3-phosphate synthase, cannot be fully repressed by inositol and choline, and UASsubINO1/sub (inositol-sensitive upstream activating sequence)-driven transcription is enhanced in Acb1p-depleted cells. In addition, the reduction in inositol-mediated repression of iINO1/i transcription observed after depletion of Acb1p appeared to be independent of the transcriptional repressor, Opi1p. We also demonstrated that iINO1/i and iOPI3/i expression can be normalized in Acb1p-depleted cells by the addition of high concentrations of exogenous fatty acids, or by the overexpression of iFAS1/i or iACC1/i. Together, these findings revealed an Acb1p-dependent connection between fatty acid metabolism and transcriptional regulation of phospholipid biosynthesis in yeast. Finally, expression of an Acb1p mutant which is unable to bind acyl-CoA esters could not normalize the transcriptional changes caused by Acb1p depletion. This strongly implied that gene expression is modulated either by the Acb1p–acyl-CoA ester complex directly or by its ability to donate acyl-CoA esters to utilizing systems./p