Sj. Smith et al., TRANSCRIPTIONAL REGULATION BY ERGOSTEROL IN THE YEAST SACCHAROMYCES-CEREVISIAE, Molecular and cellular biology, 16(10), 1996, pp. 5427-5432
Sterol biosynthesis in the yeast Saccharomyces cerevisiae is an energy
-expensive, aerobic process, requiring heme and molecular oxygen, Heme
, also synthesized exclusively during aerobic growth, not only acts as
an enzymatic cofactor but also is directly and indirectly responsible
for the transcriptional control of several yeast genes, Because of th
eir biosynthetic similarities, we hypothesized that ergosterol, like h
eme, may have a regulatory function. Sterols are known to play a struc
tural role in membrane integrity, but regulatory roles have not been c
haracterized, To test possible regulatory roles of sterol, the promote
r for the ERG3 gene, encoding the sterol C-5 desaturase, was fused to
the bacterial lacZ reporter gene, This construct was placed in strains
making aberrant sterols, and the effect of altered sterol composition
on gene expression was monitored by beta-galactosidase activity, The
absence of ergosterol resulted in a 35-fold increase in the expression
of ERG3 as measured by beta-galactosidase activity, The level of ERG3
mRNA was increased as much as ninefold in erg mutant strains or wild-
type strains inhibited in ergosterol biosynthesis by antifungal agents
, The observed regulatory effects of ergosterol on ERG3 are specific f
or ergosterol, as several ergosterol derivatives failed to elicit the
same controlling effect, These results demonstrate for the first time
that ergosterol exerts a regulatory effect on gene transcription in S.
cerevisiae.