Overproduction of the Opi1 repressor inhibits transcriptional activation of structural genes required for phospholipid biosynthesis in the yeastSaccharomyces cerevisiae

Wagner, Christian; Blank, Martina; Strohmann, Brigitte; Schüller, Hans‐Joachim

doi:10.1002/(sici)1097-0061(199907)15:10a<843::aid-yea424>3.0.co;2-m

Cited by 48 publications

(60 citation statements)

References 42 publications

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“…To test this possibility, we assayed the effect of several NuA4 component mutants on expression of an OPI1-cat reporter ( Figure 4C). As reported, the expression of the OPI1-cat reporter was repressed twofold by the addition of inositol and choline ( Jiranek et al 1998;Wagner et al 1999;Lopes 2003, 2006). However, the NuA4 component mutants did not yield reduced expression of the OPI1-cat reporter.…”

Section: A Genomewide Screen Identified 89 Opisupporting

confidence: 57%

“…One possible explanation for the Opi1 phenotype is that the NuA4 complex may act indirectly on INO1 expression by increasing OPI1 expression. This was a reasonable assumption since altered expression of OPI1 has been shown to affect target gene expression (Wagner et al 1999). To test this possibility, we assayed the effect of several NuA4 component mutants on expression of an OPI1-cat reporter ( Figure 4C).…”

Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 99%

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Genomic Analysis of the Opi− Phenotype

2006

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Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are coordinately regulated in response to inositol and choline. Inositol affects the intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the phospholipid biosynthetic genes and specifically binds PA in the endoplasmic reticulum. In the presence of inositol, PA levels decrease, releasing Opi1p into the nucleus where it represses transcription. The opi1 mutant overproduces and excretes inositol into the growth medium in the absence of inositol and choline (Opi À phenotype). To better understand the mechanism of Opi1p repression, the viable yeast deletion set was screened to identify Opi À mutants. In total, 89 Opi À mutants were identified, of which 7 were previously known to have the Opi À phenotype. The Opi À mutant collection included genes with roles in phospholipid biosynthesis, transcription, protein processing/synthesis, and protein trafficking. Included in this set were all nonessential components of the NuA4 HAT complex and six proteins in the Rpd3p-Sin3p HDAC complex. It has previously been shown that defects in phosphatidylcholine synthesis (cho2 and opi3) yield the Opi À phenotype because of a buildup of PA. However, in this case the Opi À phenotype is conditional because PA can be shuttled through a salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven new mutants present in the Opi À collection ( fun26, kex1, nup84, tps1, mrpl38, mrpl49, and opi10/yol032w) were also suppressed by choline, suggesting that these affect PC synthesis. Regulation in response to inositol is also coordinated with the unfolded protein response (UPR). Consistent with this, several Opi À mutants were found to affect the UPR (yhi9, ede1, and vps74).

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Section: A Genomewide Screen Identified 89 Opisupporting

confidence: 57%

Section: A Genomewide Screen Identified 89 Opimentioning

confidence: 99%

Genomic Analysis of the Opi− Phenotype

2006

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“…However, there is evidence that Opi1p may not be responsible for the transmission of the signal that leads to repression of INO1 in response to phospholipid precursors (Graves and Henry, 2000). Overproduction of Opi1p was shown to render wild-type yeast auxotrophic for inositol, supporting the notion that it is a negative regulator of phospholipid biosynthesis (Wagner et al, 1999).…”

Section: Introductionmentioning

confidence: 59%

IN02, A Positive Regulator of Lipid Biosynthesis, Is Essential for the Formation of Inducible Membranes in Yeast

Block-Alper

Webster

Zhou

et al. 2002

MBoC

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Expression of the 180-kDa canine ribosome receptor inSaccharomyces cerevisiae leads to the accumulation of ER-like membranes. Gene expression patterns in strains expressing various forms of p180, each of which gives rise to unique membrane morphologies, were surveyed by microarray analysis. Several genes whose products regulate phospholipid biosynthesis were determined by Northern blotting to be differentially expressed in all strains that undergo membrane proliferation. Of these, the INO2 gene product was found to be essential for formation of p180-inducible membranes. Expression of p180 in ino2Δ cells failed to give rise to the p180-induced membrane proliferation seen in wild-type cells, whereas p180 expression in ino4Δ cells gave rise to membranes indistinguishable from wild type. Thus, Ino2p is required for the formation of p180-induced membranes and, in this case, appears to be functional in the absence of its putative binding partner, Ino4p.

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“…Addition of inositol to the media of growing cells results in a rapid change in lipid metabolism, causing Opi1p to translocate to the nucleus (26). Although Opi1p does not seem to directly interact with the UAS INO element (28,29), Opi1p is potentially targeted to UAS INO -containing genes by a direct interaction with Ino2p, where it represses the transcription of genes by recruiting the histone deacetylase Sin3p (15). These observations suggest that Opi1p plays a central role in sensing metabolism and modulating the regulation of Ino2p-Ino4p target gene expression.…”

Section: Analysis Of Genome-wide Expression Regulated By Inositolmentioning

confidence: 99%

“…This drop in PA levels is directly sensed by Opi1p, a component of an endoplasmic reticulum (ER)-localized lipid sensing complex (27), causing it to dissociate from the ER and translocate to the nucleus, where it participates in the repression of target genes. Although Opi1p does not directly interact with the UAS INO sequence (28,29), it is thought to interact with Sin3p (15), a histone deacetylase that functions as a global transcriptional repressor, and Ino2p, which potentially targets it to the promoters of UAS INO -containing genes. Thus, the transcriptional regulation of UAS INO -containing genes responds not to inositol directly but instead to a metabolic signal induced when inositol participates in lipid metabolism.…”

mentioning

confidence: 99%

Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

Jesch

Zhao

Wells

et al. 2005

Journal of Biological Chemistry

117

194

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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 UAS INO 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.Phospholipids are the key structural elements of membranebounded organelles and play important roles in signaling and membrane trafficking pathways. Each membrane compartment is composed of a unique set of phospholipids whose biophysical properties contribute to the function of each organelle. Phospholipid metabolism is highly regulated by the cell, ensuring the biogenesis and growth of membranes by coordinating the relative rates of synthesis of individual phospholipids with numerous factors, such as the availability of exogenous supplies of phospholipid precursors, growth stage, and membrane trafficking (1, 2).

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Overproduction of the Opi1 repressor inhibits transcriptional activation of structural genes required for phospholipid biosynthesis in the yeastSaccharomyces cerevisiae

Cited by 48 publications

References 42 publications

Genomic Analysis of the Opi− Phenotype

Genomic Analysis of the Opi− Phenotype

IN02, A Positive Regulator of Lipid Biosynthesis, Is Essential for the Formation of Inducible Membranes in Yeast

Genome-wide Analysis Reveals Inositol, Not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

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