The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes

• Published in: Nature 2004-01, Vol.427 (6972), p.370-374
• Main Authors: Posas, Francesc, de Nadal, Eulàlia, Zapater, Meritxell, Alepuz, Paula M, Sumoy, Lauro, Mas, Glòria
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Fungal; Genes, Fungal - genetics; Genetics; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Hog1 protein; Humanities and Social Sciences; letter; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; multidisciplinary; Mutation - genetics; Oligonucleotide Array Sequence Analysis; Osmotic Pressure; Promoter Regions, Genetic - genetics; Protein Binding; Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; Ribonucleic acid; RNA; RNA Polymerase II - metabolism; Rpd3 protein; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Transcription Factors - genetics; Transcription Factors - metabolism; Yeasts
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02258

Regulation of gene expression by mitogen-activated protein kinases (MAPKs) is essential for proper cell adaptation to extracellular stimuli. Exposure of yeast cells to high osmolarity results in rapid activation of the MAPK Hog1, which coordinates the transcriptional programme required for cell survival on osmostress. The mechanisms by which Hog1 and MAPKs in general regulate gene expression are not completely understood, although Hog1 can modify some transcription factors. Here we propose that Hog1 induces gene expression by a mechanism that involves recruiting a specific histone deacetylase complex to the promoters of genes regulated by osmostress. Cells lacking the Rpd3-Sin3 histone deacetylase complex are sensitive to high osmolarity and show compromised expression of osmostress genes. Hog1 interacts physically with Rpd3 in vivo and in vitro and, on stress, targets the deacetylase to specific osmostress-responsive genes. Binding of the Rpd3-Sin3 complex to specific promoters leads to histone deacetylation, entry of RNA polymerase II and induction of gene expression. Together, our data indicate that targeting of the Rpd3 histone deacetylase to osmoresponsive promoters by the MAPK Hog1 is required to induce gene expression on stress.