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Genetic dissection of the redundant and divergent functions of histone chaperone paralogs in yeast

By Neda Savic, Shawn P. Shortill, Misha Bilenky, David Dilworth, Martin Hirst, Christopher J Nelson

Posted 24 Mar 2019
bioRxiv DOI: 10.1101/586347

Gene duplications increase organismal robustness by providing freedom for gene divergence or by increasing gene dosage. The yeast histone chaperones Fpr3 and Fpr4 are paralogs that can assemble nucleosomes in vitro, however the genomic locations they target and their functional relationship is poorly understood. We refined the yeast synthetic genetic array (SGA) approach to enable the functional dissection of gene paralogs. Applying this method to Fpr3 and Fpr4 uncovered their redundant and divergent functions: while Fpr3 is uniquely involved in chromosome segregation, Fpr3 and Fpr4 are generally redundant for regulation of gene expression and transcriptional processivity. We find that the TRAMP5 RNA exosome is essential Δfpr3Δfpr4 yeast and leveraged this information to find Fpr3/4 target loci. Amongst these are the non-transcribed spacers of ribosomal DNA where either paralog is sufficient to establish chromatin that is both transcriptionally silent and refractory to recombination. These data provide evidence that Fpr3 and Fpr4 have shared chromatin-centric functions, especially at nucleolar rDNA. However, their distinct genetic interaction profiles show they also have evolved separate functions outside of the nucleolus.

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