title: Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase.
abstract: 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.
authors.affiliation: Departments of Genetics, Pharmacology and Cancer Biology, Microbiology and Medicine, The Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arévalo-Rodríguez
authors.forename: M E
authors.initials: ME
authors.lastname: Cardenas
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: S D
authors.initials: SD
authors.lastname: Hanes
authors.forename: J
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000107:Acetylation; D004275:DNA, Ribosomal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004795:Enzyme Stability; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D020104:Immunophilins / Q000235:genetics / Q000502:physiology; D008938:Mitosis; D008954:Models, Biological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C102098:CTH1 protein, S cerevisiae; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012319:RNA Polymerase II; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases; C491869:SAP30 protein, S cerevisiae; D022021:Tacrolimus Binding Proteins; C000606845:ESS1 protein, S cerevisiae; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase