The structure of chromatin occludes much of the underlying DNA sequence. Accordingly, processes that impinge on DNA sequence, including the transcription of RNAs and the recombination, repair and replication of DNA, use histone chaperones and histone post-translational modifiers to overcome this barrier. Fpr3 and Fpr4 are yeast histone chaperones that also contain C-terminal FKBP histone prolyl isomerase domains. How these nuclear enzymes are used to regulate chromatin in vivo has not been well resolved.
Using reporter genes integrated throughout the yeast genome, as well as RNA-Seq, we find that Fpr3 and Fpr4 co-operate to establish a defined transcriptionally-silent chromatin domain within the rDNA locus. To obtain a global view of Fpr3 and Fpr4 function, we performed modified synthetic genetic interaction screens to query which biological processes are sensitive to these enzymes. These experiments revealed a synthetic lethality between Fpr4 and components of the RNA exosome; a complex that functions to degrade aberrant RNA transcripts. Together our results demonstrate that nuclear FKBPs and the RNA exosome co-operate to down-regulate RNAs generated from rDNA spacers. They also suggest that nuclear prolyl isomerases are particularly important at organizing rDNA chromatin. Finally, the effects of some chromatin modifiers on RNA expression may be masked by RNA exosome action.