title: SIR-nucleosome interactions: structure-function relationships in yeast silent chromatin.
abstract: Discrete regions of the eukaryotic genome assume a heritable chromatin structure that is refractory to gene expression, referred to as heterochromatin or "silent" chromatin. Constitutively silent chromatin is found in subtelomeric domains in a number of species, ranging from yeast to man. In addition, chromatin-dependent repression of mating type loci occurs in both budding and fission yeasts, to enable sexual reproduction. The silencing of chromatin in budding yeast is characterized by an assembly of Silent Information Regulatory (SIR) proteins-Sir2, Sir3 and Sir4-with unmodified nucleosomes. Silencing requires the lysine deacetylase activity of Sir2, extensive contacts between Sir3 and the nucleosome, as well as interactions among the SIR proteins, to generate the Sir2-3-4 or SIR complex. Results from recent structural and reconstitution studies suggest an updated model for the ordered assembly and organization of SIR-dependent silent chromatin in yeast. Moreover, studies of subtelomeric gene expression reveal the importance of subtelomeric silent chromatin in the regulation of genes other than the silent mating type loci. This review covers recent advances in this field.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Mariano
authors.initials: M
authors.lastname: Oppikofer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kueng
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D000818:Animals; D002843:Chromatin / Q000201:enzymology / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000201:enzymology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D037761:Sirtuins / Q000378:metabolism*; D015003:Yeasts / Q000201:enzymology* / Q000235:genetics
chemical_list: D002843:Chromatin; D005656:Fungal Proteins; D006657:Histones; D009707:Nucleosomes; D037761:Sirtuins
keywords: ChIP; EM; Gene silencing; HAT; HM; HMT; Histone post-translational modification; MALS; NAD; NCP; Nicotinamide Adenine Dinucleotide; O-AADPR; O-acetyl-ADP-ribose; PEV; PTM; Position Effect Variegation; SIR; SPR; Silent Information Regulator; Sir2; Sir3; Sir4; Surface Plasmon Resonance; TPE; TSS; Telomere; Telomere Position Effect; Transcriptional Start Site; aa; amino acid; base pairs; bp; chromatin immunoprecipitation; electron microscopy; histone acetyl transferase; histone methyl-transferase; homothallic mating-type loci; multi-angle light scattering; nucleosome core particle; post-translational modification