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The stress-regulatory transcription factors Msn2 and Msn4 regulate fatty acid oxidation in budding yeast.

Praveen Kumar, R. and Madhuri, A. and Ram, Rajasekharan (2017) The stress-regulatory transcription factors Msn2 and Msn4 regulate fatty acid oxidation in budding yeast. Journal of Biological Chemistry, 292 (45). pp. 18628-18643.

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Abstract

The transcription factors Msn2 and Msn4 (multicopy suppressor of SNF1 mutation proteins 2 and 4) bind the stress-response element in gene promoters in the yeast Saccharomyces cerevisiae. However, the roles of Msn2/4 in primary metabolic pathways such as fatty acid �-oxidation are unclear. Here, in silico analysis revealed that the promoters of most genes involved in the biogenesis, function, and regulation of the peroxisome contain Msn2/4-binding sites.Wealso found that transcript levels of MSN2/MSN4 are increased in glucose-depletion conditions and that during growth in nonpreferred carbon sources, Msn2 is constantly localized to the nucleus in wild-type cells. Of note, the double mutant msn2�msn4� exhibited a severe growth defect when grown with oleic acid as the sole carbon source and had reduced transcript levels of major �-oxidation genes. ChIP indicated that Msn2 has increased occupancy on the promoters of�-oxidation genes in glucose-depleted conditions, and in vivo reporter gene analysis indicated reduced expression of these genes in msn2�msn4� cells. Moreover, mobility shift assays revealed that Msn4 binds �-oxidation gene promoters. Immunofluorescence microscopy with antiperoxisome membrane protein antibodies disclosed that the msn2�msn4� strain had fewer peroxisomes than the wild type, and lipid analysis indicated that the msn2�msn4� strain had increased triacylglycerol and steryl ester levels. Collectively, our data suggest that Msn2/Msn4 transcription factors activate expression of the genes involved in fatty acid oxidation. Because glucose sensing, signaling, and fatty acid �-oxidation pathways are evolutionarily conserved throughout eukaryotes, the msn2� msn4�strain could therefore be a good model system for further study of these critical processes.

Item Type: Article
Uncontrolled Keywords: msn2, msn4, Saccharomyces cerevisiae, yeast, fatty acid beta-oxidation
Subjects: 500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 11 Lipid Biochemistry
500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 19 Yeast
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 07 Feb 2019 05:24
Last Modified: 07 Feb 2019 05:24
URI: http://ir.cftri.com/id/eprint/13941

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