Heat shock transcription factor (HSF) is an evolutionarily conserved
protein that mediates eukaryotic transcriptional responses to stress. Although the mammalian stress-responsive HSF1
isoform is activated in response to a wide array of seemingly unrelated stresses, including heat shock, pharmacological agents,
infection and
inflammation, little is known about the precise mechanisms or pathways by which this factor is activated by many stressors. The baker's yeast Saccharomyces cerevisiae encodes a single HSF
protein that responds to heat stress and
glucose starvation and provides a simple model system to investigate how a single HSF is activated by multiple stresses. Although induction of the HSF target gene CUP1 by
glucose starvation is dependent on the
Snf1 kinase, HSF-dependent heat shock induction of CUP1 is Snf1-independent. Approximately 165 in vivo targets for HSF have been identified in S. cerevisiae using
chromatin immunoprecipitation combined with
DNA microarrays. Interestingly, approximately 30% of the HSF direct target genes are also induced by the diauxic shift, in which
glucose levels begin to be depleted. We demonstrate that HSF and
Snf1 kinase interact in vivo and that HSF is a direct substrate for phosphorylation by
Snf1 kinase in vitro. Furthermore,
glucose starvation-dependent, but not heat shock-dependent HSF phosphorylation, and enhanced chromosomal HSF
DNA binding to low affinity target promoters such as SSA3 and HSP30, occurred in a Snf1-dependent manner. Consistent with a more global role for HSF and Snf1 in activating gene expression in response to changes in
glucose availability, expression of a subset of HSF targets by
glucose starvation was dependent on Snf1 and the HSF carboxyl-terminal activation domain.