A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation

High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Genes & Development (Impact Factor: 12.64). 09/2008; 22(15):2062-74. DOI: 10.1101/gad.1679508
Source: PubMed

ABSTRACT Histone acetylation and deacetylation are among the principal mechanisms by which chromatin is regulated during transcription, DNA silencing, and DNA repair. We analyzed patterns of genetic interactions uncovered during comprehensive genome-wide analyses in yeast to probe how histone acetyltransferase (HAT) and histone deacetylase (HDAC) protein complexes interact. The genetic interaction data unveil an underappreciated role of HDACs in maintaining cellular viability, and led us to show that deacetylation of the histone variant Htz1p at Lys 14 is mediated by Hda1p. Studies of the essential nucleosome acetyltransferase of H4 (NuA4) revealed acetylation-dependent protein stabilization of Yng2p, a potential nonhistone substrate of NuA4 and Rpd3C, and led to a new functional organization model for this critical complex. We also found that DNA double-stranded breaks (DSBs) result in local recruitment of the NuA4 complex, followed by an elaborate NuA4 remodeling process concomitant with Rpd3p recruitment and histone deacetylation. These new characterizations of the HDA and NuA4 complexes demonstrate how systematic analyses of genetic interactions may help illuminate the mechanisms of intricate cellular processes.

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Available from: Joel S Bader, Dec 16, 2014
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    • "See also Table S3. both Rad57 and Rad5 are required for SCR (Figure 4B), in agreement with previous reports (Mozlin et al., 2008; Zhang and Lawrence, 2005). Interestingly , SCR rates were not decreased in the hst1Dhos2Dsir2D mutant but rather were slightly increased (Figure 4B). "
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    Molecular Cell 08/2014; 55(6). DOI:10.1016/j.molcel.2014.07.007 · 14.46 Impact Factor
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    • "E-MAP was also used to map GIs in different yeast species such as Schizosaccharomyces pombe (Ryan et al., 2012). Among the other high-throughput methods to discover GIs in yeast, diploid-based synthetic lethality analysis with microarrays (dSLAM), uses a library of barcoded mutants and barcode microarrays to measure the relative abundance of each barcoded double mutants in pooled populations to identify digenic SSL interactions (Pan et al., 2006; Lin et al., 2008). Optical density measurements (St Onge et al., 2007), biomass quantification analysis termed flux balance analysis (FBA) (Segre et al., 2005), quantitative phenotype (Drees et al., 2005) and gene expression data (Van Driessche et al., 2005) have also been employed to map GIs in specific biological processes. "
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