A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation.
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.
Lin
Yu-yi
YY
High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Qi
Yan
Y
Lu
Jin-ying
JY
Pan
Xuewen
X
Yuan
Daniel S
DS
Zhao
Yingming
Y
Bader
Joel S
JS
Boeke
Jef D
JD
D000107:Acetylation; D000123:Acetyltransferases; D016000:Cluster Analysis; D004260:DNA Repair; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology
D005656:Fungal Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C469780:Yng2 protein, S cerevisiae; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae; C499673:HDA1 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases