Division of Health Sciences, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan-
Abstract: The heat shock transcription factor Hsf1 and the general stress transcription factors Msn2 and Msn4 -Msn2-4- are major regulators of the heat shock response in Saccharomyces cerevisiae- Here, we show that transcriptional activation of their target genes, including HSP104, an antistress chaperone gene, is obligatory for thermotolerance- Although Hsf1 activity might be necessary before the exposure of cells to high temperature, severe heat shock induced the binding of hyperphosphorylated Hsf1 to its target promoters- However, promoter-bound, phosphorylated Hsf1 was inactive for transcription because RNA polymerase II was inactive at high temperatures- Rather, our results suggest that Hsf1 activates the transcription of most of its target genes during the recovery period following severe heat shock- This delayed upregulation by Hsf1, which would be induced by misfolded proteins that accumulate in severely heat-shocked cells, is required for the resumption of normal cell growth- In contrast, the factors Msn2-4 were not involved in the delayed upregulation of genes and were dispensable for cell growth during the recovery period, suggesting that they play a role before the exposure to high temperature- These results show that Hsf1 and Msn2-4 act differentially before and after exposure to extreme temperatures to ensure cell survival and growth-