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(Received for publication, May 1, 1996, and in revised form, July 25, 1996)
From the Department of Biological Sciences, Carnegie Mellon
University, Pittsburgh, Pennsylvania 15213
In yeast, as in other eukaryotes,
phosphatidylcholine (PC) can be synthesized via methylation of
phosphatidylethanolamine or from free choline via the CDP-choline
pathway. In yeast, PC biosynthesis is required for the repression of
the phospholipid biosynthetic genes, including the INO1
gene, in response to inositol. In this study, we analyzed the effect of
mutations in genes encoding enzymes involved in PC biosynthesis on the
transcriptional regulation of phospholipid biosynthetic genes. We
report that repression of INO1 transcription in response to
inositol is clearly dependent on ongoing PC biosynthesis, but it is
independent of the route of synthesis. Our results also suggest that
intermediates in the phosphatidylethanolamine methylation and
CDP-choline pathways are not responsible for generating the regulatory
signal that results in repression of INO1 and other
coregulated genes of phospholipid biosynthesis. Furthermore, repression
of INO1 is not tightly correlated to the proportion of PC
in the total cellular phospholipids. Rather, we report that when the
rate of synthesis of PC becomes growth limiting, the addition of
inositol fails to repress the phospholipid biosynthetic genes, but when
the rate of PC synthesis is sufficient to sustain normal growth, the
addition of inositol to the growth medium has the effect of repressing
INO1 and other phospholipid biosynthetic genes.
Volume 271, Number 41,
Issue of October 11, 1996
pp. 25692-25698
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
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