title: Bypassing Sir2 and O-acetyl-ADP-ribose in transcriptional silencing.
abstract: The yeast Sir2/3/4 complex forms a heterochromatin-like structure that represses transcription. The proteins nucleate at silencers and spread distally, utilizing the Sir2 NAD(+)-dependent histone deacetylase activity and the affinity of Sir3/4 for deacetylated histone tails. A by-product of the Sir2 reaction, O-acetyl-ADP-ribose (OAADPr), is thought to aid spreading by binding one of the Sir proteins. We developed a protein chimera approach to reexamine the contributions of Sir2. We show that a Sir3 chimera-bearing Hos3, an unrelated NAD(+)-independent histone deacetylase, substitutes for Sir2 in silencing. Sir3-Hos3 operates within the Sir pathway, spreading while deacetylating histones. Moreover, the chimera represses HM loci in strains lacking all five OAADPr-producing deacetylases, indicating that OAADPr is not necessary for silencing. Repression by a Hos3 hybrid bearing the targeting motifs of Sir2 shows that targeting doesn't require the Sir2 reaction. Together, these data demonstrate that protein deacetylation is the only essential function of Sir2 in creating silenced chromatin.
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Chou
authors.forename: Yao-Cheng
authors.initials: YC
authors.lastname: Li
authors.forename: Marc R
authors.initials: MR
authors.lastname: Gartenberg
mesh_terms: D020868:Gene Silencing; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D038961:O-Acetyl-ADP-Ribose / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D038961:O-Acetyl-ADP-Ribose; D011993:Recombinant Fusion Proteins; C084122:SIR3 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases
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