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

ABSTRACT: 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.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE215374 | GEO | 2022/10/14

REPOSITORIES: GEO

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

Project description: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.

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Swc4 protects chromatin against genome instability and aneuploidy

Project description: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, spindle assembly check-point activation and significant increase of the Rfa1 foci and γ-H2A levels. Notably, both telomeres and rDNA loci in swc4Δ cells become unstable and are highly susceptible to recombination. Mechanistically, Swc4 interacts with chromatin likely through hypoacetylated histone H4. Taking together, we conclude that the chromatin associated Swc4 protects chromatin from breakage to ensure genome integrity.

2021-11-07 | GSE188281 | GEO

Swc4 protects nucleosome-free rDNA, tDNA and telomere loci to inhibit genome instability

Project description:In the baker’s yeast Saccharomyces cerevisiae, NuA4 and SWR1-C, two multisubunit complexes, are involved in histone acetylation and chromatin remodeling, respectively. Eaf1 is the assembly platform subunit of NuA4, Swr1 is the assembly platform and catalytic subunit of SWR1-C, while Swc4, Yaf9, Arp4 and Act1 form a functional module, and is present in both NuA4 and SWR1 complexes. ACT1 and ARP4 are essential for cell survival. Deletion of SWC4, but not YAF9, EAF1 or SWR1 results in a severe growth defect, but the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display defects in DNA ploidy and chromosome segregation, suggesting that the defects observed in swc4Δ cells are independent of NuA4 or SWR1-C integrity. Swc4 is enriched in the nucleosome-free regions (NFRs) of the genome, including characteristic regions of RDN5s, tDNAs and telomeres, independently of Yaf9, Eaf1 or Swr1. In particular, rDNA, tDNA and telomere loci are more unstable and prone to recombination in the swc4Δ cells than in wild-type cells. Taken together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin of rDNA, tDNA and telomere loci to ensure genome integrity.

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Distribution of Arp4 in G2/M phase

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Distribution of Arp4 in G2/M phase

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Gene expression data of Arabidopsis thaliana yaf9a yaf9b double mutant seedlings

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Nucleosome free DNA- and acetyl histone-binding components recruit SWR1 to yeast promoters for H2A.Z replacement

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