Subtelomeric gene silencing in Saccharomyces cerevisiae . (A) Spreading of histone deacetylation away from the telomere. Rap1 proteins associate with the telomere repeats and recruit Sir2/Sir3/Sir4 proteins. Sir2p is an enzyme that deacetylates the histones in the adjacent nucleosome. More Sir2/Sir3/Sir4 proteins are recruited by the now deacetylated nucleosome (dark octamer) to eventually spread histone deacetylation to the next nucleosome (depicted by the curved arrow above the nucleosomes). Histone deacetylation and silent information regulator (SIR) proteins can spread several kilobases away from the telomeres. (B) Subtelomeric cis-elements in S. cerevisiae. Repetitive core X and Y’ elements contain dormant origins of DNA replication (ACS, it binds origin recognition complex, ORC), internal telomeric sequences (ITS, they bind Rap1 proteins), chromatin boundaries (depicted by B, and subtelomeric anti-silencing regions (STARs). (C) Chromatin boundaries restrict the spreading of histone deacetylation and prevent the silencing of telomere-distal genes (red arrows). (D) ITS and ACS are protosilencers, which extend the spreading of SIR proteins or confer telomere-dependent silencing of genes (white arrows) beyond an active subtelomeric gene (red arrow). A hypothetical STAR and a chromatin boundary contribute to the maintenance of the active gene. ORC, origin recognition complex; SIR, silent information regulator.