Histone H3 specific acetyltransferases are essential for cell cycle progression

Howe, LeAnn; Auston, Darryl A.; Grant, Patrick A.; John, Sam; Cook, Richard G.; Workman, Jerry L.; Pillus, Lorraine

doi:10.1101/gad.931401

Cited by 209 publications

(214 citation statements)

References 71 publications

(89 reference statements)

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“…The Esa1 H4 HAT is also essential for yeast cell viability (40,41). The cell cycle delays we observe here upon mutation of H3 Ser 10 and loss of GCN5 are highly reminiscent of those observed in our previous studies (21,34) and those observed by Howe et al (39) upon loss of GCN5 and SAS3. One simple explanation is that the lowered acetylation of Lys 9 that occurs upon Ser 10 mutation becomes critical upon loss of other acetylation events mediated by Gcn5.…”

Section: Discussionsupporting

confidence: 73%

See 1 more Smart Citation

Site-specific Loss of Acetylation upon Phosphorylation of Histone H3

Edmondson¹,

Davie²,

Zhou³

et al. 2002

Journal of Biological Chemistry

101

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Post-translational modification of histones is a central aspect of gene regulation. Emerging data indicate that modification at one site can influence modification of a second site. As one example, histone H3 phosphorylation at serine 10 (Ser 10 ) facilitates acetylation of lysine 14 (Lys 14 ) by Gcn5 in vitro (1, 2). In vivo, phosphorylation of H3 precedes acetylation at certain promoters. Whether H3 phosphorylation globally affects acetylation, or whether it affects all acetylation sites in H3 equally, is not known. We have taken a genetic approach to this question by mutating Ser 10 in H3 to fix either a negative or a neutral charge at this position, followed by analysis of the acetylation states of the mutant histones using site-specific antibodies. Surprisingly, we find that conversion of Ser 10 to glutamate (S10E) or aspartate (S10D) causes almost complete loss of H3 acetylation at lysine 9 (Lys 9 ) in vivo. Acetylation of Lys 9 is also significantly reduced in cells bearing mutations in the Glc7 phosphatase that increase H3 phosphorylation levels. Mutation of Ser 10 in H3 and the concomitant loss of Lys 9 acetylation has minimal effects on expression of a Gcn5-dependent reporter gene. However, synergistic growth defects are observed upon loss of GCN5 in cells bearing H3 Ser 10 mutations that are reminiscent of delays in G 2 /M progression caused by combined loss of GCN5 and acetylation site mutations. Together these results demonstrate that H3 phosphorylation directly causes sitespecific and opposite changes in acetylation levels of two residues within this histone, Lys 9 and Lys 14 , and they highlight the importance of these histone modifications to normal cell functions.

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Section: Discussionsupporting

confidence: 73%

“…These studies indicated that a certain threshold of acetylation events is required for normal cell cycle progression. Consistent with this idea, concomitant loss of the genes encoding the Gcn5 and Sas3 H3 HAT activities is lethal in yeast (39). The Esa1 H4 HAT is also essential for yeast cell viability (40,41).…”

Section: Discussionsupporting

confidence: 64%

Site-specific Loss of Acetylation upon Phosphorylation of Histone H3

Edmondson¹,

Davie²,

Zhou³

et al. 2002

Journal of Biological Chemistry

101

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“…These observations suggest that RSC is not dedicated to cell cycle regulation, although we cannot exclude the possibility that G 2 /M arrest is caused by defective expression of a key G 2 /M-specific gene(s). Interestingly, mutations in histone tails or in other chromatin-modifying activities (e.g., histone acetylases), arrest cells at the G 2 /M transition or slow progression through G 2 /M (Megee et al 1990;Morgan et al 1991;Zhang et al 1998;Clarke et al 1999;Howe et al 2001). …”

Section: Rsc1 and Rsc2 Forms Of The Rsc Complex Associate With Commonmentioning

confidence: 99%

Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex

Ng¹,

Robert²,

Young³

et al. 2002

Genes Dev.

254

292

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Genome-wide location analysis indicates that the yeast nucleosome-remodeling complex RSC has ∼700 physiological targets and that the Rsc1 and Rsc2 isoforms of the complex behave indistinguishably. RSC is associated with numerous tRNA promoters, suggesting that the complex is recruited by the RNA polymerase III transcription machinery. At RNA polymerase II promoters, RSC specifically targets several gene classes, including histones, small nucleolar RNAs, the nitrogen discrimination pathway, nonfermentative carbohydrate metabolism, and mitochondrial function. At the histone HTA1/HTB1 promoter, RSC recruitment requires the Hir1 and Hir2 corepressors, and it is associated with transcriptional inactivity. In contrast, RSC binds to promoters involved in carbohydrate metabolism in response to transcriptional activation, but prior to association of the Pol II machinery. Therefore, the RSC complex is generally recruited to Pol III promoters and it is specifically recruited to Pol II promoters by transcriptional activators and repressors.

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“…As deletion of no single subunit defining modules or complexes recapitulated the synthetic lethality of gas1 gcn5 at 30°, it is likely that Gcn5 catalytic activity itself is the critical factor in the interaction with Gas1, as is observed for the gcn5 sas3 synthetic lethality (Howe et al 2001).…”

Section: Resultsmentioning

confidence: 99%

“…Gcn5 and Sas3 share nucleosomal H3 targets (reviewed in Lafon et al 2007) and deletion of both GCN5 and SAS3 is synthetically lethal (Howe et al 2001). Further, both Gcn5 and Sas3 are recruited to similar genomic regions (Rosaleny et al 2007).…”

mentioning

confidence: 99%

Unexpected Function of the Glucanosyltransferase Gas1 in the DNA Damage Response Linked to Histone H3 Acetyltransferases in Saccharomyces cerevisiae

Eustice

Pillus

2014

Genetics

Self Cite

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Chromatin organization and structure are crucial for transcriptional regulation, DNA replication, and damage repair. Although initially characterized in remodeling cell wall glucans, the b-1,3-glucanosyltransferase Gas1 was recently discovered to regulate transcriptional silencing in a manner separable from its activity at the cell wall. However, the function of Gas1 in modulating chromatin remains largely unexplored. Our genetic characterization revealed that GAS1 had critical interactions with genes encoding the histone H3 lysine acetyltransferases Gcn5 and Sas3. Specifically, whereas the gas1 gcn5 double mutant was synthetically lethal, deletion of both GAS1 and SAS3 restored silencing in Saccharomyces cerevisiae. The loss of GAS1 also led to broad DNA damage sensitivity with reduced Rad53 phosphorylation and defective cell cycle checkpoint activation following exposure to select genotoxins. Deletion of SAS3 in the gas1 background restored both Rad53 phosphorylation and checkpoint activation following exposure to genotoxins that trigger the DNA replication checkpoint. Our analysis thus uncovers previously unsuspected functions for both Gas1 and Sas3 in DNA damage response and cell cycle regulation.

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Histone H3 specific acetyltransferases are essential for cell cycle progression

Cited by 209 publications

References 71 publications

Site-specific Loss of Acetylation upon Phosphorylation of Histone H3

Site-specific Loss of Acetylation upon Phosphorylation of Histone H3

Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex

Unexpected Function of the Glucanosyltransferase Gas1 in the DNA Damage Response Linked to Histone H3 Acetyltransferases in Saccharomyces cerevisiae

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