title: Global analysis of SUMO chain function reveals multiple roles in chromatin regulation.
abstract: Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich resource strongly implicates SUMO chains in the regulation of chromatin. Indeed, using several different approaches, we demonstrate that SUMO chains are required for the maintenance of normal higher-order chromatin structure and transcriptional repression of environmental stress response genes in budding yeast.
authors.affiliation: Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Tharan
authors.initials: T
authors.lastname: Srikumar
authors.forename: Megan C
authors.initials: MC
authors.lastname: Lewicki
authors.forename: Michael
authors.initials: M
authors.lastname: Costanzo
authors.forename: Johnny M
authors.initials: JM
authors.lastname: Tkach
authors.forename: Harm
authors.initials: H
authors.lastname: van Bakel
authors.forename: Kyle
authors.initials: K
authors.lastname: Tsui
authors.forename: Erica S
authors.initials: ES
authors.lastname: Johnson
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Andrews
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation / Q000502:physiology*
chemical_list: D002843:Chromatin; D012331:RNA, Fungal; D012333:RNA, Messenger; C099362:SMT3 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins
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