title: Dissociation of the H3K36 demethylase Rph1 from chromatin mediates derepression of environmental stress-response genes under genotoxic stress in Saccharomyces cerevisiae.
abstract: Cells respond to environmental signals by altering gene expression through transcription factors. Rph1 is a histone demethylase containing a Jumonji C (JmjC) domain and belongs to the C(2)H(2) zinc-finger protein family. Here we investigate the regulatory network of Rph1 in yeast by expression microarray analysis. More than 75% of Rph1-regulated genes showed increased expression in the rph1-deletion mutant, suggesting that Rph1 is mainly a transcriptional repressor. The binding motif 5'-CCCCTWA-3', which resembles the stress response element, is overrepresented in the promoters of Rph1-repressed genes. A significant proportion of Rph1-regulated genes respond to DNA damage and environmental stress. Rph1 is a labile protein, and Rad53 negatively modulates Rph1 protein level. We find that the JmjN domain is important in maintaining protein stability and the repressive effect of Rph1. Rph1 is directly associated with the promoter region of targeted genes and dissociated from chromatin before transcriptional derepression on DNA damage and oxidative stress. Of interest, the master stress-activated regulator Msn2 also regulates a subset of Rph1-repressed genes under oxidative stress. Our findings confirm the regulatory role of Rph1 as a transcriptional repressor and reveal that Rph1 might be a regulatory node connecting different signaling pathways responding to environmental stresses.
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Liang
authors.forename: Long-Chi
authors.initials: LC
authors.lastname: Wang
authors.forename: Wan-Sheng
authors.initials: WS
authors.lastname: Lo
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics; D064447:Checkpoint Kinase 2 / Q000737:chemistry / Q000235:genetics; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D056466:Histone Demethylases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; C400296:RPH1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D056466:Histone Demethylases; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae