Osmotic stress-induced gene expression in Saccharomyces cerevisiae requires Msn1p and the novel nuclear factor Hot1p

After a sudden shift to high osmolarity, Saccharomyces cerevisiae cells res pond by transiently inducing the expression of stress-protective genes. Msn 2p and Msn4p have been described as two transcription factors that determin e the extent of this response. In msn2 msn4 mutants, however, many promoter s still show a distinct rise in transcriptional activity upon osmotic stres s. Here we describe two structurally related nuclear factors, Msn1p and a n ewly identified protein, Hot1p (for high-osmolarity-induced transcription), which are also involved in osmotic stress-induced transcription. hot1 sing le mutants are specifically compromised in the transient induction of GPD1 and GPP2, which encode enzymes involved in glycerol biosynthesis, and exhib it delayed glycerol accumulation after stress exposure. Similar to a gpd1 m utation, a hot1 defect can rescue cells from inappropriately high HOG pathw ay activity. In contrast, Hot1p has little influence on the osmotic stress induction of CTT1, where Msn1p appears to play a more prominent role. Cells lacking Msn1p, Msn2p, Msn4p, and Hot1p are almost devoid of the short-term transcriptional response of the genes GPD1, GPP2, CTT1, and HSP12 to osmot ic stress. Such cells also show a distinct reduction in the nuclear residen ce of the mitogen-activated protein kinase Hog1p upon osmotic stress. Thus, Hot1p and Msn1p may define an additional tier of transcriptional regulator s that control responses to high-osmolarity stress.