Practice question

Telomeric position effect in budding yeast involves Sir complex spreading from chromosome ends inward silencing subtelomeric genes. Rap1 protein binds TG1-3 telomere repeats recruiting Sir4 which interacts with Sir2 histone deacetylase. Sir2 deacetylates adjacent nucleosomal H4K16 and H3K9, generating high-affinity binding site for Sir3 chromodomain interacting with deacetylated tails, recruiting additional Sir2-Sir4 complexes iteratively propagating heterochromatin several kilobases. This histone deacetylation dependent polymerization requires continuous Sir2 NAD-dependent activity, blocked by boundary elements or acetyltransferases. Disruption of deacetylation restores acetylation evicting Sir proteins activating normally silent loci, illustrating requirement for histone deacetylation in spreading and maintenance of telomeric heterochromatin inheritance.