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PMID:10899127

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Citation

Arévalo-Rodríguez, M, Cardenas, ME, Wu, X, Hanes, SD and Heitman, J (2000) Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase. EMBO J. 19:3739-49

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.

Links

PubMed PMC313981 Online version:10.1093/emboj/19.14.3739

Keywords

Acetylation; DNA, Ribosomal/genetics; DNA-Binding Proteins/metabolism; Enzyme Stability; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Fungal; Gene Silencing; Genes, Fungal/genetics; Genes, Lethal/genetics; Histone Deacetylase Inhibitors; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Immunophilins/genetics; Immunophilins/physiology; Mitosis; Models, Biological; Peptidylprolyl Isomerase/genetics; Peptidylprolyl Isomerase/metabolism; RNA Polymerase II/metabolism; Repressor Proteins; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins; Suppression, Genetic; Tacrolimus Binding Proteins; Transcription Factors/antagonists & inhibitors; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:ESS1

located_in

GO:0005634: nucleus

ECO:0000305: curator inference used in manual assertion

GO:0031064
GO:2000749

C

Seeded From UniProt

complete

YEAST:ESS1

involved_in

GO:2000749: positive regulation of rDNA heterochromatin assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:ESS1

involved_in

GO:0031064: negative regulation of histone deacetylation

ECO:0000353: physical interaction evidence used in manual assertion

SGD:S000004876
SGD:S000005274

P

Seeded From UniProt

complete

YEAST:ESS1

involved_in

GO:0031064: negative regulation of histone deacetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:ESS1

part_of

GO:0005634: nucleus

ECO:0000305: curator inference used in manual assertion

GO:0031064
GO:2000749

C

Seeded From UniProt

complete

YEAST:ESS1

involved_in

GO:2000749: positive regulation of chromatin silencing at rDNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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