Epigenetics in Saccharomyces cerevisiae

Saccharomyces cerevisiae provides a well-studied model system for heritable silent chromatin, in which a nonhistone protein complex-the SIR complex-represses genes by spreading in a sequence-independent manner, much like heterochromatin in higher eukaryotes. The ability to study mutations in histones and to screen genome-wide for mutations that impair silencing has yielded an unparalleled depth of detail about this system. Recent advances in the biochemistry and structural biology of the SIR-chromatin complex bring us much closer to a molecular understanding of how Sir3 selectively recognizes the deacetylated histone H4 tail and demethylated histone H3 core. The existence of appropriate mutants has also shown how components of the silencing machinery affect physiological processes beyond transcriptional repression. Outline 1 The genetic and molecular tools of yeast 2 The life cycle of yeast 3 Yeast heterochromatin is present at the silent HM mating loci and at telomeres 4 Sir protein structure and evolutionary conservation 5 Silent chromatin is distinguished by a repressive structure that spreads through the entire domain 6 Distinct steps in heterochromatin assembly 7 The crucial role of histone H4K16 acetylation and its deacetylation by Sir2 8 Barrier functions: Histone modifications restrict Sir complex spreading 9 A role for the H3 amino-terminal tail in higherorder chromatin structures 10 Trans-interaction of telomeres, and perinuclear attachment of heterochromatin 11 Telomere looping 12 Variable repression at natural subtelomeric domains 13 Inheritance of epigenetic states 14 Other functions of Sir proteins and silent chromatin 15