Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
ReviewTranscriptional regulation of yeast phospholipid biosynthetic genes
Section snippets
Transcriptional regulation of INO1 expression
The de novo synthesis of phosphatidylinositol (PI) from glucose-6-phosphate requires the INO1 structural gene that encodes inositol-3-phosphate synthase (IPS) (Fig. 1) [1], [2]. IPS is responsible for the conversion of glucose-6-phosphate to inositol-3-phosphate, which is then dephosphorylated to produce inositol [3], [4]. INO1 is regulated at the level of transcription by the soluble precursors inositol and choline. INO1 is maximally expressed in the absence of inositol and choline, partially
Transcriptional regulation of PIS1 expression
The final step in the de novo synthesis of PI requires the essential PIS1 structural gene that encodes PI synthase (PIS) (Fig. 1) [76], [77], [78], [79], [80]. PIS catalyzes the formation of PI from inositol and CDP-DAG (Fig. 1) [81], [82]. Transcriptional regulation of the PIS1 gene is understudied relative to that of the other phospholipid structural genes. This is partly because its expression is not coordinated with other phospholipid biosynthetic genes in response to inositol and choline
Transcriptional regulation of de novo PC synthesis
In Saccharomyces cerevisiae, PC can be synthesized using the CDP-diacylglycerol (CDP-DAG) de novo pathway (Fig. 1). De novo synthesis requires five genes (Fig. 1). While most of these genes are also regulated in response to inositol and choline, they have not been studied to nearly the same degree as INO1. However, several other transcription factors have been defined mostly by genome-wide strategies.
Transcriptional regulation of the PC Kennedy pathway
The Kennedy pathway utilizes ethanolamine (E) and choline (C) to synthesize PC (Fig. 1) [123]. There are six structural genes in this pathway and some of them are highly regulated in response to inositol and choline. The EKI1 and CKI1 genes are required in the first steps in the Kennedy pathway. EKI1 and CKI1 encode ethanolamine kinase and choline kinase, respectively. Both genes are regulated at the transcriptional level in response to inositol and choline in a pattern similar to that of INO1
Ino2p and Ino4p
It is generally accepted that INO2 gene is auto-regulated in response to inositol and choline. Several studies show that INO2 transcript levels, INO2-lacZ and INO2-cat reporters, and Ino2p protein levels are repressed ∼12-fold in response to inositol and choline [39], [63], [127], [128], [129], [130], [131], [132], [133], [134], [135]. However, there is one study that reports constitutive expression of Ino2p protein levels in a wild type strain [17]. The reason for this discrepancy was not
Future directions
Considerable strides have been made in recent years towards understanding the mechanisms that regulate transcription of the phospholipid structural and regulatory genes. However, many new questions emerge from these developments. The regulation of INO1 transcription is remarkable in that it involves a large number of transcription factors that bind DNA and/or regulate chromatin structure. Why there is a need for so many factors remains to be answered. It will be important to determine if these
Acknowledgements
We thank members of the Lopes lab for helpful discussions and assistance with editing. We also thank Dr. George Carman (Rutgers Univ.) for his longtime support and encouragement. We are grateful to our colleague down the hall, Dr. Miriam Greenberg, for being a constant source of inspiration and to members of her lab for continuous discussions. We are also grateful for the reviewers' helpful comments. Work in the Lopes lab is supported by a grant from the National Science Foundation to J.M.L.
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2014, Chemistry and Physics of LipidsCitation Excerpt :The cellular consequences of inositol depletion have also been studied in mammalian cells and compared to yeast in the context of exposure to inositol depleting drugs lithium and valproic acid (Deranieh and Greenberg, 2009). Various aspects of regulation and signaling related to lipid and inositol metabolism in yeast have been extensively reviewed (Carman and Han, 2011; Carman and Henry, 1999; Chen et al., 2007; Dickson, 2008; Gaspar et al., 2007; Greenberg and Lopes, 1996; Henneberry and Sturley, 2005; Henry et al., 2012; Jesch and Henry, 2005; Majerus and York, 2009; Strahl and Thorner, 2007; Tsui and York, 2010). Thus it is not the intention of this article to provide a comprehensive coverage of the broader topics of lipid and inositol metabolism in regulation and signaling in eukaryotic cells in general.
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These authors contributed equally to this work.