The silencing factor Sir3 clusters together the ends of yeast chromosomes, Ruault et al. report.
Yeast telomeres gather into distinct subcompartments near the nuclear periphery, thereby concentrating the gene-silencing factors that bind them. This improves the silencing of genes lying near chromosome ends, while avoiding inappropriate repression of genes located elsewhere in the genome. Silencing may in turn regulate clustering, because deleting components of the Sir2–Sir3–Sir4 silencing complex disrupts telomere organization.
Ruault et al. overexpressed individual subunits of the Sir2–Sir3–Sir4 complex to investigate which of them was responsible for aggregating telomeres. Sir3 overexpression bunched telomeres into larger foci than those found in wild-type cells and repressed genes in subtelomeric regions more stably. Silencing wasn't required for telomere clustering to occur, however. Overexpression of a Sir3 mutant lacking silencing activity still induced large telomere clusters, even in the absence of Sir2 and Sir4. But deleting the telomeric protein Rap1 blocked the Sir3 mutant's recruitment to chromosome ends and prevented it from inducing telomere hyperclustering.
Because Sir3 can oligomerize with itself, Ruault et al. think that neighboring telomeres are held together by arrays of the protein at chromosome ends. Mammalian telomeres normally don't cluster, but different chromatin proteins may act similarly to organize other parts of the genome.
Although silencing isn't required for clustering, Sir3’s involvement in both processes ensures that telomere organization and function are tightly linked. Senior author Angela Taddei now wants to investigate whether environmental changes that affect gene silencing also regulate telomere aggregation.
