The NuA4 Core Complex Acetylates Nucleosomal Histone H4 through a Double Recognition Mechanism

Xu, Peng; Li, Chengmin; Chen, Zhihong; Jiang, Shuangying; Fan, Shilong; Wang, Jiawei; Dai, Junbiao; Zhu, Ping; Chen, Zhucheng

doi:10.1016/j.molcel.2016.07.024

Cited by 69 publications

(80 citation statements)

References 69 publications

(98 reference statements)

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“…Most recently, the structure of the EPcA domain was solved in complex with the other piccolo-NuA4 subunits, and the first bypass mutant of EPL1 was identified using genetic suppression analysis that has been so powerful for the study of many critical proteins and biological processes (Hughes 2016; Prelich 1999; van Leeuwen et al 2017 ). These studies, building on earlier suppression of non-null alleles (Lin et al 2008), implicated Epl1 as being a critical Esa1 co-factor, and highlighted the importance of the physical Epl1-Esa1 interactions for acetyltransferase activity (Searle et al 2017; Xu et al 2016). …”

Section: Comparative Studies Between Model Organisms Promote Functionmentioning

confidence: 91%

“…Building on earlier work, recent, mutagenesis- and structure-based studies in S. cerevisiae have assigned function to many residues of Epl1 (Searle et al 2017; Xu et al 2016), promoting a great expansion in understanding the importance of specific residues and their corresponding roles. Similar studies in other organisms might prove fruitful.…”

Section: An Eye To the Futurementioning

confidence: 99%

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Critical genomic regulation mediated by Enhancer of Polycomb

Searle

Pillus

2017

Curr Genet

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Enhancer of Polycomb (EPC) was first identified for its contributions to development in Drosophila and was soon-thereafter purified as a subunit of the NuA4/TIP60 acetyltransferase complex. Since then, EPC has often been left in the shadows as an essential, yet non-catalytic subunit of NuA4/TIP60; however, its deep conservation and disease association make clear that it warrants additional attention. In fact, recent studies in yeast demonstrated that its Enhancer of Polycomb, Epl1, was just as important for gene expression and acetylation as is the catalytic subunit of NuA4. Despite its conservation, studies of EPC have often remained siloed between organisms. Here, our goal is to provide a cohesive view of the current state of the EPC literature as it stands among the major model organisms in which it has been studied. EPC is involved in multiple processes, beginning with its cardinal role in regulating global and targeted histone acetylation. EPC also frequently serves as an important interaction partner in these basic cellular functions, as well as in multicellular development, such as in hematopoiesis and skeletal muscle differentiation, and in human disease. Taken together, a unifying theme from these studies highlights EPC as a critical genomic regulator.

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Section: Comparative Studies Between Model Organisms Promote Functionmentioning

confidence: 91%

Section: An Eye To the Futurementioning

confidence: 99%

Critical genomic regulation mediated by Enhancer of Polycomb

Searle

Pillus

2017

Curr Genet

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“…Despite these advantages, identifying small NCP particles in vitreous ice can be challenging, and most cryo-EM NCP structures to date have been visualized with added mass, either from bulky post-transitional modifications (Wilson et al, 2016) or in complex with large protein assemblies (Maskell et al, 2015;Yamada et al, 2011;Xu et al, 2016). Chua and coworkers circumvented this problem by using a Volta phase plate, allowing increased contrast at low spatial frequencies and improved particle alignment (Chua et al, 2016).…”

Section: Visualizing Nucleosomes Under the Electron Microscopementioning

confidence: 99%

“…(a) PFV intasome-NCP structure (EMD entry 2992; Maskell et al, 2015). (b) NuA4 acetylase-NCP structure (EMD entry 9536; Xu et al, 2016). (c) 53BP1-NCP-ubme structure (EMD entry 8246; Wilson et al, 2016).…”

Section: Visualizing Nucleosomes Under the Electron Microscopementioning

confidence: 99%

Cryo-electron microscopy of chromatin biology

Wilson

Costa

2017

Acta Cryst Sect D Struct Biol

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The basic unit of chromatin, the nucleosome core particle (NCP), controls how DNA in eukaryotic cells is compacted, replicated and read. Since its discovery, biochemists have sought to understand how this protein-DNA complex can help to control so many diverse tasks. Recent electron-microscopy (EM) studies on NCP-containing assemblies have helped to describe important chromatin transactions at a molecular level. With the implementation of recent technical advances in single-particle EM, our understanding of how nucleosomes are recognized and read looks to take a leap forward. In this review, the authors highlight recent advances in the architectural understanding of chromatin biology elucidated by EM.

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“…Transcription-Associated 1 (TRA1) recruit reader subunits and transcription factors, greatly improving specificity of the acetyltransferase subunit Essential SAS2-related Acetyltransferase 1 (ESA1) towards histones H4, H2A and H2A.Z in the chromatin context [13][14][15][16] . Molecular studies in yeast and animals support critical roles for the NuA4-dependent histone acetylation in DNArepair and transcription 17,18 .…”

Section: Introductionmentioning

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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The NuA4 Core Complex Acetylates Nucleosomal Histone H4 through a Double Recognition Mechanism

Cited by 69 publications

References 69 publications

Critical genomic regulation mediated by Enhancer of Polycomb

Critical genomic regulation mediated by Enhancer of Polycomb

Cryo-electron microscopy of chromatin biology

Nuclear encoded photosynthesis genes are specifically controlled by the NuA4 complex

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