GCN5-dependent histone H3 acetylation and RPD3-dependent histone H4 deacetylation have distinct, opposing effects on IME2 transcription, during meiosis and during vegetative growth, in budding yeast

Diploid yeast undergo meiosis under certain conditions of nutrient limitati on, which trigger a transcriptional cascade involving two key regulatory ge nes. IME1 is a positive activator of IME2, which activates downstream genes . We report that Gcn5, a histone H3 acetylase, plays a central role in init iation of meiosis via effects on IME2 expression. An allele, gcn5-21, was i solated as a mutant defective in spore formation. gcn5-21 fails to carry ou t meiotic DNA replication, recombination, or meiotic divisions. This mutant also fails to induce IME2 transcription; IME1 transcription, however, is e ssentially normal. Further investigation shows that during wild-type meiosi s the IME2 promoter undergoes an increase in the level of bound acetylated histone H3, This increase is contemporaneous with meiotic induction of IME2 transcription and is absent in gcn5-21, In contrast, the RPD3 gene, which encodes a histone H4 deacetylase and is known to be required for repression of basal IME2 transcription in growing yeast cells, is not involved in ind uction of IME2 transcription or IME2 histone acetlyation during meiosis, Th ese and other results suggest that Gcn5 and Rpd3 play distinct roles, modul ating transcription initiation in opposite directions under two different c ellular conditions. These roles are implemented via opposing effects of the two gene products on acetylation of two different histones, Finally, we fi nd that gcn5 and rpd3 single mutants are not defective in meiosis if acetat e is absent and respiration is promoted by a metabolically unrelated carbon source. Perhaps intracellular acetate levels regulate meiosis by controlli ng histone acetylation patterns.