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Dissociation of the H3K36 demethylase Rph1 from chromatin mediates derepression of environmental stress-response genes under genotoxic stress in Saccharomyces cerevisiae.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2013 Oct; Vol. 24 (20), pp. 3251-62. Date of Electronic Publication: 2013 Aug 28. - Publication Year :
- 2013
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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.
- Subjects :
- Cell Cycle Proteins chemistry
Cell Cycle Proteins genetics
Checkpoint Kinase 2 chemistry
Checkpoint Kinase 2 genetics
Chromatin genetics
Chromatin metabolism
Gene Expression Regulation, Fungal
Gene Regulatory Networks
Histone Demethylases chemistry
Histone Demethylases metabolism
Histones chemistry
Histones genetics
Histones metabolism
Promoter Regions, Genetic
Protein Binding
Repressor Proteins chemistry
Repressor Proteins metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins chemistry
Saccharomyces cerevisiae Proteins metabolism
Signal Transduction
Chromatin chemistry
DNA Damage genetics
Histone Demethylases genetics
Repressor Proteins genetics
Saccharomyces cerevisiae Proteins genetics
Stress, Physiological genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1939-4586
- Volume :
- 24
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 23985319
- Full Text :
- https://doi.org/10.1091/mbc.E12-11-0820