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Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3–Rpd3 histone deacetylase
Author(s) -
ArévaloRodríguez Miguel,
Cardenas Maria E.,
Wu Xiaoyun,
Hanes Steven D.,
Heitman Joseph
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.14.3739
Subject(s) - biology , hdac11 , histone deacetylase , histone deacetylase 2 , histone deacetylase 5 , hdac4 , hdac10 , cyclophilin a , sap30 , gene silencing , hdac1 , histone , microbiology and biotechnology , genetics , gene
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.