Swc4 protects nucleosome free chromatin of telomeres, tRNA genes and rDNA loci to inhibit genome instability [ATAC-seq]

In the baker’s yeast Saccharomyces cerevisiae, Swc4, Yaf9, Arp4, and Act1 form a submodule shared by histone acetylation NuA4 complex and chromatin remodeling SWR1 complex (SWR1-C). Act1 and Arp4 are essential for cell survival. Deletion of SWC4, but not YAF9, results in severe growth defect, however, the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display mitotic defects in both faithful chromosome segregation and DNA ploidy, suggesting that the defects observed in swc4Δ cells are independent of the integrity of either NuA4 or SWR1-C. Additionally, loss of Swc4 function results in chromosomal breakage and spindle assembly check-point activation. Swc4 binds to telomeres, tRNA and rDNA regions in genome, which represent nucleosome free regions (NFRs) of chromatin. Notably, telomeres, tRNA genes and rDNA loci, in swc4Δ cells become unstable and are highly susceptible to recombination. Taking together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin from breakage to ensure genome integrity. ATAC-seq assays to examine the chromatin accessibility using hyperactive Tn5 transposase in logarithmic wide-type and swc4Δ cells