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

Three families of prolyl isomerases have been identified: cyclophilins, FK5 06-binding proteins (FKBPs) and parvulins, All 12 cyclophilins and FKBPs ar e 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 enz ymatic activity is required for suppression. These results indicate that cy clophilin A and Ess1 function in parallel pathways and act on common target s by a mechanism that requires prolyl isomerization, Using genetic and bioc hemical approaches, we found that one of these targets is the Sin3-Rpd3 his tone deacetylase complex, and that cyclophilin A increases and Ess1 decreas es disruption of gene silencing by this complex. We show that conditions th at favor acetylation over deacetylation suppress ess1 mutations. Our findin gs support a model in which Ess1 and cyclophilin A modulate the activity of the Sin3-Rpd3 complex, and excess histone deacetylation causes mitotic arr est in ess1 mutants.