title: The yeast Snt2 protein coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress.
abstract: Regulation of gene expression is a vital part of the cellular stress response, yet the full set of proteins that orchestrate this regulation remains unknown. Snt2 is a Saccharomyces cerevisiae protein whose function has not been well characterized that was recently shown to associate with Ecm5 and the Rpd3 deacetylase. Here, we confirm that Snt2, Ecm5, and Rpd3 physically associate. We then demonstrate that cells lacking Rpd3 or Snt2 are resistant to hydrogen peroxide (H2O2)-mediated oxidative stress and use chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to show that Snt2 and Ecm5 recruit Rpd3 to a small number of promoters and in response to H2O2, colocalize independently of Rpd3 to the promoters of stress response genes. By integrating ChIP-seq and expression analyses, we identify target genes that require Snt2 for proper expression after H2O2. Finally, we show that cells lacking Snt2 are also resistant to nutrient stress imparted by the TOR (target of rapamycin) pathway inhibitor rapamycin and identify a common set of genes targeted by Snt2 and Ecm5 in response to both H2O2 and rapamycin. Our results establish a function for Snt2 in regulating transcription in response to oxidative stress and suggest Snt2 may also function in multiple stress pathways.
authors.affiliation: Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, New York, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Baker
authors.forename: Beatrix M
authors.initials: BM
authors.lastname: Ueberheide
authors.forename: Scott
authors.initials: S
authors.lastname: Dewell
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015151:Immunoblotting; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020123:Sirolimus / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004268:DNA-Binding Proteins; C584400:Ecm5 protein, S cerevisiae; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; C577606:Snt2 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases; D020123:Sirolimus