Transcriptional repression by the histone tails in budding yeast is mediated by Rpd3, Tup1-Ssn6, and Bur6/NC2

Chromatin-mediated transcriptional regulation is modulated by post-translational modifications of the core histones, particularly the H3 and H4 unstructured amino termini, or "tails". In budding yeast, the H3 and H4 tails can be deacetylated by Rpd3 to repress specific target genes, and hypoacetylated histones can facilitate recruitment of the Tup1-Ssn6 complex to effect gene repression. However, the extent to which these mechanisms are used to effect repression by the histone tails, and whether other factors similarly collaborate with the tails to facilitate gene repression, has not been determined. Here, a chromatin modifier compendium of 170 gene expression profiles from yeast strains mutated for chromatin-related genes was used to query the effect of the corresponding mutations on gene cohorts repressed by the histone H3 and H4 tails and/or by Rpd3. The resulting analysis reveals that repression of nearly all of the genes repressed by the histone tails requires Rpd3 and/or the Tup1-Ssn6 complex. Repression by Rpd3 occurs via the Rpd3-L complex, and TFIID-dominated genes are underrepresented among genes repressed by mutations or deletions of the H3 or H4 tails, in accord with previous work. In addition, Bur6, the yeast homolog of human NC2α, is required for repression at ∼50 % of genes repressed by the H3 or H4 tail. These results illuminate genome-wide repression mechanisms utilized by the histone tails in yeast and raise new questions regarding the role of Bur6 in histone tail-mediated repression and whether parallels exist in metazoan cells.