title: Genome-wide analysis of functional sirtuin chromatin targets in yeast.
abstract: BACKGROUND
  The sirtuins are a conserved family of NAD⁺-dependent histone/protein deacetylases that regulate numerous cellular processes, including heterochromatin formation and transcription. Multiple sirtuins are encoded by each eukaryotic genome, raising the possibility of cooperativity or functional overlap. The scope and variety of chromatin binding sites of the sirtuins in any specific organism remain unclear.
  
  
  RESULTS
  Here we utilize the ChIP-seq technique to identify and functionally characterize the genome-wide targets of the sirtuins, Sir2, Hst1 to Hst4, and the DNA binding partner of Hst1, Sum 1, in Saccharomyces cerevisiae. Unexpectedly, Sir2, Hst1 and Sum1, but not the other sirtuins, exhibit co-enrichment at several classes of chromatin targets. These include telomeric repeat clusters, tRNA genes, and surprisingly, the open reading frames (ORFs) of multiple highly expressed RNA polymerase II-transcribed genes that function in processes such as fermentation, glycolysis, and translation. Repression of these target genes during the diauxic shift is specifically dependent on Sir2/Hst1/Sum1 binding to the ORF and sufficiently high intracellular NAD⁺ concentrations. Sir2 recruitment to the ORFs is independent of the canonical SIR complex and surprisingly requires Sum1. The shared Sir2/Hst1/Sum1 targets also significantly overlap with condensin and cohesin binding sites, where Sir2, Hst1, and Sum1 were found to be important for condensin and cohesin deposition, suggesting a possible mechanistic link between metabolism and chromatin architecture during the diauxic shift.
  
  
  CONCLUSIONS
  This study demonstrates the existence of overlap in sirtuin function, and advances our understanding of conserved sirtuin-regulated functions, including the regulation of glycolytic gene expression and condensin loading.
authors.forename: Mingguang
authors.initials: M
authors.lastname: Li
authors.forename: Veena
authors.initials: V
authors.lastname: Valsakumar
authors.forename: Kunal
authors.initials: K
authors.lastname: Poorey
authors.forename: Stefan
authors.initials: S
authors.lastname: Bekiranov
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Smith
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016681:Genome, Fungal; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D000097722:Cohesins; C100925:SUM1 protein, S cerevisiae; C108312:condensin complexes; C103934:HST1 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae