title: Exploring the yeast acetylome using functional genomics.
abstract: Lysine acetylation is a dynamic posttranslational modification with a well-defined role in regulating histones. The impact of acetylation on other cellular functions remains relatively uncharacterized. We explored the budding yeast acetylome with a functional genomics approach, assessing the effects of gene overexpression in the absence of lysine deacetylases (KDACs). We generated a network of 463 synthetic dosage lethal (SDL) interactions involving class I and II KDACs, revealing many cellular pathways regulated by different KDACs. A biochemical survey of genes interacting with the KDAC RPD3 identified 72 proteins acetylated in vivo. In-depth analysis of one of these proteins, Swi4, revealed a role for acetylation in G1-specific gene expression. Acetylation of Swi4 regulates interaction with its partner Swi6, both components of the SBF transcription factor. This study expands our view of the yeast acetylome, demonstrates the utility of functional genomic screens for exploring enzymatic pathways, and provides functional information that can be mined for future studies.
authors.affiliation: Department of Molecular Genetics, The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada.
authors.forename: Supipi
authors.initials: S
authors.lastname: Kaluarachchi Duffy
authors.forename: Helena
authors.initials: H
authors.lastname: Friesen
authors.forename: Anastasia
authors.initials: A
authors.lastname: Baryshnikova
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lambert
authors.forename: Yolanda T
authors.initials: YT
authors.lastname: Chong
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D023281:Genomics; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C062214:SWI4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases