The negative regulator Opi1 of phospholipid biosynthesis in yeast contacts the pleiotropic repressor Sin3 and the transcriptional activator Ino2

Wagner, Christian; Dietz, M; Wittmann, Jürgen; Albrecht, A.; Schüller, Hans‐Joachim

doi:10.1046/j.1365-2958.2001.02495.x

Cited by 107 publications

(177 citation statements)

References 60 publications

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“…When wild type cells are grown in the presence of zinc but in the absence of inositol, the Ino2p-Ino4p complex binds the UAS INO element to drive transcription for maximum gene expression (13,24,26,100). When cells are grown with zinc and supplemented with inositol, Opi1p represses transcription by binding to DNA-bound Ino2p (127). Like CHO1, the UAS INOcontaining INO1 gene was repressed by zinc depletion although inositol was absent from the growth medium.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn

Han

Carman

2004

Journal of Biological Chemistry

156

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Zinc is an essential nutrient required for the growth and metabolism of eukaryotic cells. In this work, we examined the effects of zinc depletion on the regulation of phospholipid synthesis in the yeast Saccharomyces cerevisiae. Zinc depletion resulted in a decrease in the activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. In contrast, the activity of phosphatidylinositol synthase was elevated in response to zinc depletion. The level of Aut7p, a marker for the induction of autophagy, was also elevated in zinc-depleted cells. For the CHO1-encoded phosphatidylserine synthase, the reduction in activity in response to zinc depletion was controlled at the level of transcription. This regulation was mediated through the UAS INO element and by the transcription factors Ino2p, Ino4p, and Opi1p that are responsible for the inositol-mediated regulation of UAS INO -containing genes involved in phospholipid synthesis. Analysis of the cellular composition of the major membrane phospholipids showed that zinc depletion resulted in a 66% decrease in phosphatidylethanolamine and a 29% increase in phosphatidylinositol. A zrt1⌬ zrt2⌬ mutant (defective in the plasma membrane zinc transporters Zrt1p and Zrt2p) grown in the presence of zinc exhibited a phospholipid composition similar to that of wild type cells depleted for zinc. These results indicated that a decrease in the cytoplasmic levels of zinc was responsible for the alterations in phospholipid composition.

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Section: Discussionmentioning

confidence: 99%

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn

Han

Carman

2004

Journal of Biological Chemistry

156

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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%

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

120

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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“…Nonetheless, despite the continual binding of Ino2p/Ino4p to UAS INO , inositol suppresses transcriptional activation via the Opi1p repressor. Opi1p mediates repression via its activator interaction domain, which binds to the repressor interaction domain of Ino2p (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

A SWI/SNF- and INO80-dependent nucleosome movement at the INO1 promoter

Ford

Odeyale

Eskandar

et al. 2007

Biochemical and Biophysical Research Communications

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Transcriptional activation in yeast INO1 chromatin was studied using the indirect end-labeling technique. INO1 chromatin is organized into an ordered, overlapping nucleosomal array under repressing conditions. Nucleosome positions were only disrupted at the promoter region under inducing conditions in the presence of SWI/SNF and INO80. Mutants lacking either remodeler demonstrated identical positioning patterns as the wild type under repressing conditions. This indicates that these two remodelers are responsible and essential for local nucleosomal mobilization at the INO1 promoter. The area of local nucleosome movement is consistent with the previously identified region of histone deacetylation activity. In light of these findings, we suggest that nucleosomes subject to local mobilization are also targets for local histone modifications.

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The negative regulator Opi1 of phospholipid biosynthesis in yeast contacts the pleiotropic repressor Sin3 and the transcriptional activator Ino2

Cited by 107 publications

References 60 publications

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

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

A SWI/SNF- and INO80-dependent nucleosome movement at the INO1 promoter

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