Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast

Eukaryotic genomes are packaged into nucleosomes, which are thought to repr ess gene expression generally(1-3), Repression is particularly evident at y east telomeres, where genes within the telomeric heterochromatin appear to be silenced by the histone-binding silent information regulator (SIR) compl ex (Sir2, Sir3, Sir4) and Rap1 (refs 4-10). Here, to investigate how nucleo somes and silencing factors influence global gene expression, we use high-d ensity arrays to study the effects of depleting nucleosomal histones and si lencing factors in yeast. Reducing nucleosome content by depleting histone H4 caused increased expression of 15% of genes and reduced expression of 10 % of genes, hut it had little effect on expression of the majority (75%) of yeast genes, Telomere-proximal genes were found to be de-repressed over re gions extending 20 kilobases from the telomeres, well beyond the extent of Sir protein binding(11,12) and the effects of loss of Sir function, These r esults indicate that histones make Sir-independent contributions to telomer ic silencing, and that the role of histones located elsewhere in chromosome s is gene specific rather than generally repressive.