Eaf1 Links the NuA4 Histone Acetyltransferase Complex to Htz1 Incorporation and Regulation of Purine Biosynthesis

Cheng, Xue; Auger, Andréanne; Altaf, Mohammed; Drouin, Simon; Paquet, Éric R.; Utley, Rhea T.; Robert, François; Côté, Jacques

doi:10.1128/ec.00004-15

Cited by 15 publications

(20 citation statements)

References 50 publications

(85 reference statements)

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“…Upregulated genes common to previous eaf1 Δ transcriptome studies and our sec14-1 ts eaf1 Δ transcriptome included the stress response genes ( DDR2 , HSP12 , HSP26 ) (Lindstrom et al 2006; Cheng et al 2015). Together, these results indicate that deletion of EAF1 in the sec14-1 ts background impacts the transcriptome similar to what has been previously reported for NuA4 mutants in the wild-type background.…”

Section: Resultsmentioning

confidence: 99%

NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis inSaccharomyces cerevisiae

Dacquay

Flint

Butcher

et al. 2017

G3 Genes|Genomes|Genetics

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Actively proliferating cells constantly monitor and readjust their metabolic pathways to ensure the replenishment of phospholipids necessary for membrane biogenesis and intracellular trafficking. In Saccharomyces cerevisiae, multiple studies have suggested that the lysine acetyltransferase complex NuA4 plays a role in phospholipid homeostasis. For one, NuA4 mutants induce the expression of the inositol-3-phosphate synthase gene, INO1, which leads to excessive accumulation of inositol, a key metabolite used for phospholipid biosynthesis. Additionally, NuA4 mutants also display negative genetic interactions with sec14-1ts, a mutant of a lipid-binding gene responsible for phospholipid remodeling of the Golgi. Here, using a combination of genetics and transcriptional profiling, we explore the connections between NuA4, inositol, and Sec14. Surprisingly, we found that NuA4 mutants did not suppress but rather exacerbated the growth defects of sec14-1ts under inositol-depleted conditions. Transcriptome studies reveal that while loss of the NuA4 subunit EAF1 in sec14-1ts does derepress INO1 expression, it does not derepress all inositol/choline-responsive phospholipid genes, suggesting that the impact of Eaf1 on phospholipid homeostasis extends beyond inositol biosynthesis. In fact, we find that NuA4 mutants have impaired lipid droplet levels and through genetic and chemical approaches, we determine that the genetic interaction between sec14-1ts and NuA4 mutants potentially reflects a role for NuA4 in fatty acid biosynthesis. Altogether, our work identifies a new role for NuA4 in phospholipid homeostasis.

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Section: Resultsmentioning

confidence: 99%

NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis inSaccharomyces cerevisiae

Dacquay

Flint

Butcher

et al. 2017

G3 Genes|Genomes|Genetics

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“…While the NuA4 complex was first demonstrated to be recruited to specific gene promoters, where it locally acetylates nucleosomal histones (9,14,15,18), more recent studies have shown that NuA4 is also present on actively transcribed coding sequences (open reading frames [ORFs]) (19,20). Its enrichment at promoters correlates with an increase of histone acetylation and chromatin relaxation, allowing access to DNA for the transcription machinery, and its targeting to promoters is thought to be mediated by transcription activators (13,15,21,31). However, NuA4 harbors several subunits carrying PTM-binding motifs (Fig.…”

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confidence: 99%

“…NuA4 acetylates lysines on the N-terminal tails of H4, H2A, and H2AZ (Htz1) histones (7,(9)(10)(11)(12), and its histone acetyltransferase (HAT) activity is important for the regulation of gene transcription (13)(14)(15)(16)(17)(18)(19)(20)(21) and also for the cellular response to DNA dam-age, recombination, and DNA double-strand break repair (22)(23)(24)(25)(26)(27). More recently, NuA4 was also shown to regulate life span and autophagy through its ability to acetylate nonhistone proteins (28)(29)(30).…”

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confidence: 99%

Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome

Steunou

Cramet

Rossetto

et al. 2016

Molecular and Cellular Biology

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e Recognition of histone marks by reader modules is thought to be at the heart of epigenetic mechanisms. These protein domains are considered to function by targeting regulators to chromosomal loci carrying specific histone modifications. This is important for proper gene regulation as well as propagation of epigenetic information. The NuA4 acetyltransferase complex contains two of these reader modules, an H3K4me3-specific plant homeodomain (PHD) within the Yng2 subunit and an H3K36me2/3-specific chromodomain in the Eaf3 subunit. While each domain showed a close functional interaction with the respective histone mark that it recognizes, at the biochemical level, genetic level (as assessed with epistatic miniarray profile screens), and phenotypic level, cells with the combined loss of both readers showed greatly enhanced phenotypes. Chromatin immunoprecipitation coupled with next-generation sequencing experiments demonstrated that the Yng2 PHD specifically directs H4 acetylation near the transcription start site of highly expressed genes, while Eaf3 is important downstream on the body of the genes. Strikingly, the recruitment of the NuA4 complex to these loci was not significantly affected. Furthermore, RNA polymerase II occupancy was decreased only under conditions where both PHD and chromodomains were lost, generally in the second half of the gene coding regions. Altogether, these results argue that methylated histone reader modules in NuA4 are not responsible for its recruitment to the promoter or coding regions but, rather, are required to orient its acetyltransferase catalytic site to the methylated histone 3-bearing nucleosomes in the surrounding chromatin, cooperating to allow proper transition from transcription initiation to elongation. Chromatin is a dynamic nucleoprotein structure that compacts the long DNA molecule into the small nuclear space, simultaneously creating a mechanism to regulate DNA access to machineries implicated in essential nuclear processes, namely, transcription, DNA replication, DNA repair, and meiotic recombination. Modulation of the chromatin structure is highly regulated by four broad classes of nuclear factors: chromatin remodelers, histone chaperones, histone variants, and histone modifiers. These players essentially target nucleosomes, basic units of chromatin consisting of 146 bp of DNA wrapped around an octamer of histone proteins. Histone modifiers catalyze posttranslational modifications (PTM), including acetylation, phosphorylation, and methylation, that can directly affect DNA-histone contacts (e.g., acetylation) and/or create a binding platform for PTM readers (1, 2). These readers correspond to proteins/complexes containing distinct domains/modules that can bind specific modified histone residues. Such motifs include bromodomains that recognize acetylated residues; chromodomains (CHD); PWWP, Tudor, and MBT domains for methylated residues; BRCT, BIR, and 14-3-3 domains for phosphorylated histones; and plant homeodomain (PHD) fingers that can bind different modification...

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“…In yeast, certain groups of genes show high NuA4-dependence. These are mostly genes involved in translation and other anabolic processes 18,33,40,47,48 . Consistently, NuA4-defficient yeast strains are hypersensitive to rapamycin which inhibits growth-promoting TOR signaling 14 .…”

Section: Discussionmentioning

confidence: 99%

Nuclear encoded photosynthesis genes are specifically controlled by the NuA4 complex

Bieluszewski

Sura

Bieluszewska

et al. 2019

Preprint

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NuA4, an essential histone acetyltransferase complex, is required for efficient transcription in eukaryotes. Using genome editing, genomic approaches and biochemical assays, we characterized plant homologues of two key components of this complex, EPL1 and EAF1 in Arabidopsis thaliana. Surprisingly, we found that loss of AtEPL1, which is necessary for enzymatic activity of NuA4, is not lethal. Contrary to yeast, mutants lacking AtEAF1, responsible for complex targeting, display severe pleiotropic phenotype which copies that of Atepl1. Atepl1 and Ateaf1 mutants grow slowly, contain reduced chlorophyll levels and small chloroplasts. We provide evidence that these alterations are not caused by incapacitation of GLK transcription factors, the major regulators of chloroplast development. Using ChIP-seq we show that H4 acetylation levels are dramatically reduced in the chromatin of the Atepl1 mutant, while H3 acetylation remains mostly unchanged. We use our data to define NuA4-dependent genes and show that chloroplast-related genes are significantly overrepresented in this group, consistent with the pale-green phenotypes of the mutants. We propose that NuA4 was adopted in plants to control nuclear-encoded photosynthesis genes.

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Eaf1 Links the NuA4 Histone Acetyltransferase Complex to Htz1 Incorporation and Regulation of Purine Biosynthesis

Cited by 15 publications

References 50 publications

NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis inSaccharomyces cerevisiae

NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis inSaccharomyces cerevisiae

Combined Action of Histone Reader Modules Regulates NuA4 Local Acetyltransferase Function but Not Its Recruitment on the Genome

Nuclear encoded photosynthesis genes are specifically controlled by the NuA4 complex

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