Schizosaccharomyces pombe is becoming an increasingly useful organism for the study of cellular processes, since in certain respects, such as the cell cycle and splicing, it is similar to metazoans. Previous biochemical studies have shown that the DNA binding ability of S. pombe heat shock factor (HSF) is fully induced only under stressed conditions, in a manner similar to that of Drosophila melanogaster and humans but differing from the constitutive binding by HSF in the budding yeasts. We report the isolation of the cDNA and gene for the HSF from S. pombe. S. pombe HSF has a domain structure that is more closely related to the structure of human and D. The mechanism by which eukaryotic cells respond to heat shock is highly conserved (reviewed in references 21 and 24). This response, which also protects cells from numerous other forms of stress, is presumed to have been conserved throughout evolution because the ability of a cell to survive stress is critical to its viability in a natural setting. A major aspect of the heat shock response is the transcriptional induction of the genes that encode the heat shock proteins. This induction is regulated by heat shock factor (HSF), a transcription factor whose DNA binding site (the heat shock element [HSE]) is similar in all studied eukaryotes. This binding site is found in the promoter regions of heat shock genes and consists of inverted repeats of the sequence nGAAn (3,27,45). Binding of HSF to this site results in 20-to 1,000-fold transcriptional stimulation, depending on the specific promoter and cell type. The potent transcriptional stimulatory properties of HSF, the conserved nature of the heat shock response, and the importance of this response to cellular physiology have caused HSF to be an intensively studied factor.The regulation of HSF following stress has been compared in several eukaryotic organisms. In the budding yeast Saccharomyces cerevisiae, HSF is constitutively bound to the HSE, and heat shock increases the degree of transcriptional stimulation attributed to HSF (14,37,39,40). This increase in transcriptional stimulatory ability is believed to be regulated by posttranslational modification of S. cerevisiae HSF (37, 40). There is a correlation between increased phosphorylation of the molecule and increased transcription of the heat shock genes, and it has therefore been proposed that phosphorylation might regulate transcriptional stimulation * Corresponding author. t Present address: Immunogen, Cambridge, MA 02139.by this HSF. Study of a related budding yeast, Kluyveromyces lactis, identified a conserved seven-amino-acid sequence in HSF that is necessary for appropriate regulation of the transcriptional stimulatory properties of S. cerevisiae and K lactis HSFs (15). The precise role that this seven-amino-acid sequence plays in regulating HSF has not been elucidated. Budding yeast HSF is one of the factors responsible for maintaining basal (nonstressed) expression from certain heat shock promoters, in part because of its ability to constitutively bin...