Functional Divergence between Histone Deacetylases in Fission Yeast by Distinct Cellular Localization and In Vivo Specificity

• DOI: 10.1128/mcb.22.7.2170-2181.2002
• Publication Date: 2002-07-27T09:58:35Z
• Authors: Pernilla Bjerling; Rebecca A. Silver...; Geneviève Thon; Amy Caudy; Shiv Grewal; Karl Ekwall
• Keywords: Heterochromatin protein 1; Schizosaccharomyces; Euchromatin

Histone deacetylases (HDACs) are important for gene regulation and the maintenance of heterochromatin in eukaryotes.Schizosaccharomyces pombe was used as a model system to investigate functional divergence within this conserved enzyme family.S. has three HDACs encoded by hda1 ؉ , clr3 clr6 genes.Strains mutated these genes have previously been shown display strikingly different phenotypes when assayed viability, chromosome loss, silencing.Here, differences substrate binding pocket identify Clr6 Hda1 class I HDACs, while Clr3 belongs II family.Furthermore, were subcellular localization patterns.Hda1 localized cytoplasm, most resided throughout nucleus.Finally, exclusively on chromosomes spotted pattern.Interestingly, Clr3, only HDAC present nucleolus, required ribosomal DNA (rDNA) silencing.Clr3 presumably acts directly heterochromatin, since it colocalized with centromere, mating-type region, rDNA visualized situ hybridization.In addition, could be cross-linked mat3 chromatin immunoprecipitation experiments.Western analysis bulk histone preparations indicated that (class I) had generally low level activity vivo high broad specificity, whereas II) displayed its main acetylated lysine 14 H3.Thus, distinct functions S. likely explained their cellular specificities.