The transcription factor GCN4 regulates PHM8 and alters triacylglycerol metabolism in Saccharomyces cerevisiae

PHM8 is a very important enzyme in nonpolar
lipid metabolism because of its role in triacylglycerol
(TAG) biosynthesis under phosphate stress conditions. It is
positively regulated by the PHO4 transcription factor under
low phosphate conditions; however, its regulation has not
been explored under normal physiological conditions.
General control nonderepressible (GCN4), a basic leucinezipper
transcription factor activates the transcription of
amino acids, purine biosynthesis genes and many stress
response genes under various stress conditions. In this
study, we demonstrate that the level of TAG is regulated by
the transcription factor GCN4. GCN4 directly binds to its
consensus recognition sequence (TGACTC) in the PHM8
promoter and controls its expression. The analysis of
cells expressing the PPHM8-lacZ reporter gene showed that
mutations (TGACTC–GGGCCC) in the GCN4-binding
sequence caused a significant increase in β-galactosidase
activity. Mutation in the GCN4 binding sequence causes an
increase in PHM8 expression, lysophosphatidic acid phosphatase
activity and TAG level. PHM8, in conjunction with
DGA1, a mono- and diacylglycerol transferase, controls the
level of TAG. These results revealed that GCN4 negatively
regulates PHM8 and that deletion of GCN4 causes derepression
of PHM8, which is responsible for the increased
TAG content in gcn4Δ cells.