Abstract
In the yeast Saccharomyces cerevisiae, the transcription of many genes encoding enzymes of phospholipid biosynthesis are repressed in cells grown in the presence of the phospholipid precursors inositol and choline. A genome-wide approach using cDNA microarray technology was used to profile the changes in the expression of all genes in yeast that respond to the exogenous presence of inositol and choline. We report that the global response to inositol is completely distinct from the effect of choline. Whereas the effect of inositol on gene expression was primarily repressing, the effect of choline on gene expression was activating. Moreover, the combination of inositol and choline increased the number of repressed genes compared with inositol alone and enhanced the repression levels of a subset of genes that responded to inositol. In all, 110 genes were repressed in the presence of inositol and choline. Two distinct sets of genes exhibited differential expression in response to inositol or the combination of inositol and choline in wild-type cells. One set of genes contained the UASINO sequence and were bound by Ino2p and Ino4p. Many of these genes were also negatively regulated by OPI1, suggesting a common regulatory mechanism for Ino2p, Ino4p, and Opi1p. Another nonoverlapping set of genes was coregulated by the unfolded protein response pathway, an ER-localized stress response pathway, but was not dependent on OPI1 and did not show further repression when choline was present together with inositol. These results suggest that inositol is the major effector of target gene expression, whereas choline plays a minor role.
Highlights
Phospholipids are the key structural elements of membranebounded organelles and play important roles in signaling and membrane trafficking pathways
We show that OPI1 primarily regulates genes that were previously shown by Lee et al [38] to contain a bound Ino2p and Ino4p, and these genes are distinct from those genes regulated by the unfolded protein response (UPR) pathway
Global Analysis of Inositol and Choline on Gene Expression in Yeast—Previous studies have shown that the presence of phospholipid precursors in the medium of logarithmically growing cultures of Saccharomyces cerevisiae regulates the transcriptional response of a number of genes. These genes include those encoding the structural enzymes for phospholipid biosynthesis [4] as well as genes encoding protein folding chaperones induced by the UPR pathway [51]
Summary
Phospholipids are the key structural elements of membranebounded organelles and play important roles in signaling and membrane trafficking pathways. The synchronized expression of these genes requires the participation of Ino2p and Ino4p, basic helix-loop-helix transcription factors that bind as a heterodimer to a cis-acting element in the promoters of these genes called UASINO, as well as Opi1p, a negative regulator of transcription (6 –15). Many of these UASINO-containing genes are maximally derepressed when the phospholipid precursors inositol and choline are absent from the growth medium in logarithmically growing cultures (16 – 25), suggesting a common regulatory mechanism [4]. Recent work from our laboratory has suggested that under certain conditions, UPR activation is not coupled to activation of UASINO-containing genes [35, 36]
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