Record Details

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

IR@CSIR-CFTRI

View Archive Info
 
 
Field Value
 
Relation http://ir.cftri.com/13941/
https://dx.doi.org/10.1074/jbc.M117.801704
 
Title The stress-regulatory transcription factors Msn2 and Msn4
regulate fatty acid oxidation in budding yeast.
 
Creator Praveen Kumar, R.
Madhuri, A.
Ram, Rajasekharan
 
Subject 11 Lipid Biochemistry
19 Yeast
 
Description 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.
 
Date 2017
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13941/1/J.%20Biol.%20Chem.-2017-Rajvanshi-18628-43.pdf
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.