Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase.

Three families of prolyl isomerases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are dispensable for growth in yeast, whereas the one parvulin homolog, Ess1, is essential. We report here that cyclophilin A becomes essential when Ess1 function is compromised. We also show that ...
overexpression of cyclophilin A suppresses ess1 conditional and null mutations, and that cyclophilin A enzymatic activity is required for suppression. These results indicate that cyclophilin A and Ess1 function in parallel pathways and act on common targets by a mechanism that requires prolyl isomerization. Using genetic and biochemical approaches, we found that one of these targets is the Sin3-Rpd3 histone deacetylase complex, and that cyclophilin A increases and Ess1 decreases disruption of gene silencing by this complex. We show that conditions that favor acetylation over deacetylation suppress ess1 mutations. Our findings support a model in which Ess1 and cyclophilin A modulate the activity of the Sin3-Rpd3 complex, and excess histone deacetylation causes mitotic arrest in ess1 mutants.
Mesh Terms:
Acetylation, DNA, Ribosomal, DNA-Binding Proteins, Enzyme Stability, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Fungal, Gene Silencing, Genes, Fungal, Genes, Lethal, Histone Deacetylase Inhibitors, Histone Deacetylases, Immunophilins, Mitosis, Models, Biological, Peptidylprolyl Isomerase, RNA Polymerase II, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Suppression, Genetic, Tacrolimus Binding Proteins, Transcription Factors
EMBO J.
Date: Jul. 17, 2000
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