Direct regulation of nucleosome density by the conserved AAA-ATPase Yta7

Lombardi, Laura M.; Ellahi, Aisha; Rine, Jasper

doi:10.1073/pnas.1116819108

Cited by 40 publications

(68 citation statements)

References 82 publications

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“…Rsc2 and Yta7 have been implicated in preventing heterochromatin spreading, and Yta7 can be detected near chromatin boundaries (Jambunathan et al 2005;Tackett et al 2005;Raisner and Madhani 2008). Although Rsc2 and Yta7 have roles in other processes such as DSB repair (Rsc2) and gene transcription (Yta7) (Kurat et al 2011;Lombardi et al 2011;Chambers et al 2012), it is tempting to speculate that mutations that reduce levels of either H3K79Me and H4K16Ac may suppress the phenotypes of hst3D hst4D cells in part by modulating the activity of Rsc2 and Yta7. The precise molecular mechanisms involved are currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Interplay Between Histone H3 Lysine 56 Deacetylation and Chromatin Modifiers in Response to DNA Damage

et al. 2015

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In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56Ac) is present in newly synthesized histones deposited throughout the genome during DNA replication. The sirtuins Hst3 and Hst4 deacetylate H3K56 after S phase, and virtually all histone H3 molecules are K56 acetylated throughout the cell cycle in hst3D hst4D mutants. Failure to deacetylate H3K56 causes thermosensitivity, spontaneous DNA damage, and sensitivity to replicative stress via molecular mechanisms that remain unclear. Here we demonstrate that unlike wild-type cells, hst3D hst4D cells are unable to complete genome duplication and accumulate persistent foci containing the homologous recombination protein Rad52 after exposure to genotoxic drugs during S phase. In response to replicative stress, cells lacking Hst3 and Hst4 also displayed intense foci containing the Rfa1 subunit of the single-stranded DNA binding protein complex RPA, as well as persistent activation of DNA damage-induced kinases. To investigate the basis of these phenotypes, we identified histone point mutations that modulate the temperature and genotoxic drug sensitivity of hst3D hst4D cells. We found that reducing the levels of histone H4 lysine 16 acetylation or H3 lysine 79 methylation partially suppresses these sensitivities and reduces spontaneous and genotoxin-induced activation of the DNA damage-response kinase Rad53 in hst3D hst4D cells. Our data further suggest that elevated DNA damage-induced signaling significantly contributes to the phenotypes of hst3D hst4D cells. Overall, these results outline a novel interplay between H3K56Ac, H3K79 methylation, and H4K16 acetylation in the cellular response to DNA damage.KEYWORDS DNA damage repair and checkpoint response; H3 lysine 56 acetylation; H3 lysine 79 methylation; H4 lysine 16 acetylation; chromatin structure C HROMATIN structure influences major DNA metabolic processes such as transcription, DNA replication, and DNA repair (Wurtele and Verreault 2006;Campos and Reinberg 2009). The basic building block of chromatin is the nucleosome core particle composed of 147 bp of DNA wrapped around the surface of a protein octamer consisting of two molecules each of histones H2A, H2B, H3, and H4. During DNA replication, preexisting (old) histones are segregated onto sister chromatids, while new histones are deposited onto replicated DNA in order to restore normal nucleosome density on nascent sister chromatids (Ransom et al. 2010;Li and Zhang 2012). In humans, newly synthesized histones H3 and H4 are acetylated on multiple residues within their N-terminal tails (Ruiz-Carrillo et al. 1975;Benson et al. 2006;Jasencakova et al. 2010) and then are deacetylated following their incorporation into chromatin (Jackson et al. 1976;

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Section: Discussionmentioning

confidence: 99%

Interplay Between Histone H3 Lysine 56 Deacetylation and Chromatin Modifiers in Response to DNA Damage

et al. 2015

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“…Subsequently, we conducted H3 ChIP analysis of these four genes in various mutants with defects in the catalytic subunits of remodeling complexes SWI/SNF (Snf2) or RSC (Sth1), Gcn5, cofactors required for H3K56 acetylation (Rtt109/Asf1), or histone chaperones Nap1 or yFACT (Spt16). We also examined mutant chaperones in the Hsp90 family (Hsp82/Hsc82), Hsp70 family (Ssa1/Ssa2), the Hsp40 cochaperone Ydj1 implicated in nucleosome eviction of GAL genes , and a mutant lacking chromatin-associated AAA-ATPase Yta7 (Gradolatto et al 2008;Lombardi et al 2011Lombardi et al , 2015. Aiming to identify mutations that impair H3 eviction without reducing Gcn4 binding, we conducted Gcn4 ChIP analysis in the same mutants.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide cooperation by HAT Gcn5, remodeler SWI/SNF, and chaperone Ydj1 in promoter nucleosome eviction and transcriptional activation

Qiu

Chereji

et al. 2015

Genome Res.

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Chaperones, nucleosome remodeling complexes, and histone acetyltransferases have been implicated in nucleosome disassembly at promoters of particular yeast genes, but whether these cofactors function ubiquitously, as well as the impact of nucleosome eviction on transcription genome-wide, is poorly understood. We used chromatin immunoprecipitation of histone H3 and RNA polymerase II (Pol II) in mutants lacking single or multiple cofactors to address these issues for about 200 genes belonging to the Gcn4 transcriptome, of which about 70 exhibit marked reductions in H3 promoter occupancy on induction by amino acid starvation. Examining four target genes in a panel of mutants indicated that SWI/SNF, Gcn5, the Hsp70 cochaperone Ydj1, and chromatin-associated factor Yta7 are required downstream from Gcn4 binding, whereas Asf1/Rtt109, Nap1, RSC, and H2AZ are dispensable for robust H3 eviction in otherwise wild-type cells. Using ChIP-seq to interrogate all 70 exemplar genes in single, double, and triple mutants implicated Gcn5, Snf2, and Ydj1 in H3 eviction at most, but not all, Gcn4 target promoters, with Gcn5 generally playing the greatest role and Ydj1 the least. Remarkably, these three cofactors cooperate similarly in H3 eviction at virtually all yeast promoters. Defective H3 eviction in cofactor mutants was coupled with reduced Pol II occupancies for the Gcn4 transcriptome and the most highly expressed uninduced genes, but the relative Pol II levels at most genes were unaffected or even elevated. These findings indicate that nucleosome eviction is crucial for robust transcription of highly expressed genes but that other steps in gene activation are more rate-limiting for most other yeast genes.

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“…Yta7 is a putative ATP-dependent remodeling protein containing a bromodomain that binds preferentially to the tail domain of H3 (Gradolatto et al 2009). However, Yta7 has little effect on histone mRNA levels, and its activities are not confined to the histone genes: it has direct effects on many inducible genes (Lombardi et al 2011). It has been proposed that Yta7 acts post-translationally, probably by regulating the amount of H3 in chromatin (Lombardi et al 2011).…”

Section: Mechanisms Of Histone Gene Regulationmentioning

confidence: 99%

Regulation of Histone Gene Expression in Budding Yeast

Eriksson¹,

Ganguli²,

Nagarajavel³

et al. 2012

Genetics

116

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We discuss the regulation of the histone genes of the budding yeast Saccharomyces cerevisiae. These include genes encoding the major core histones (H3, H4, H2A, and H2B), histone H1 (HHO1), H2AZ (HTZ1), and centromeric H3 (CSE4). Histone production is regulated during the cell cycle because the cell must replicate both its DNA during S phase and its chromatin. Consequently, the histone genes are activated in late G1 to provide sufficient core histones to assemble the replicated genome into chromatin. The major core histone genes are subject to both positive and negative regulation. The primary control system is positive, mediated by the histone gene-specific transcription activator, Spt10, through the histone upstream activating sequences (UAS) elements, with help from the major G1/S-phase activators, SBF (Swi4 cell cycle box binding factor) and perhaps MBF (MluI cell cycle box binding factor). Spt10 binds specifically to the histone UAS elements and contains a putative histone acetyltransferase domain. The negative system involves negative regulatory elements in the histone promoters, the RSC chromatin-remodeling complex, various histone chaperones [the histone regulatory (HIR) complex, Asf1, and Rtt106], and putative sequence-specific factors. The SWI/SNF chromatin-remodeling complex links the positive and negative systems. We propose that the negative system is a damping system that modulates the amount of transcription activated by Spt10 and SBF. We hypothesize that the negative system mediates negative feedback on the histone genes by histone proteins through the level of saturation of histone chaperones with histone. Thus, the negative system could communicate the degree of nucleosome assembly during DNA replication and the need to shut down the activating system under replication-stress conditions. We also discuss post-transcriptional regulation and dosage compensation of the histone genes.

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Direct regulation of nucleosome density by the conserved AAA-ATPase Yta7

Cited by 40 publications

References 82 publications

Interplay Between Histone H3 Lysine 56 Deacetylation and Chromatin Modifiers in Response to DNA Damage

Interplay Between Histone H3 Lysine 56 Deacetylation and Chromatin Modifiers in Response to DNA Damage

Genome-wide cooperation by HAT Gcn5, remodeler SWI/SNF, and chaperone Ydj1 in promoter nucleosome eviction and transcriptional activation

Regulation of Histone Gene Expression in Budding Yeast

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