Structure and flexibility of the yeast NuA4 histone acetyltransferase complex

The NuA4 protein complex acetylates histones H4 and H2A to activate both transcription and DNA repair. We report the 3.1-Å resolution cryo-electron microscopy structure of the central hub of NuA4, which flexibly tethers the histone acetyltransferase (HAT) and Trimer Independent of NuA4 involved in T...

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Bibliographic Details
Published in:eLife 2022-10, Vol.11
Main Authors: Zukin, Stefan A, Marunde, Matthew R, Popova, Irina K, Soczek, Katarzyna M, Nogales, Eva, Patel, Avinash B
Format: Article
Language:English
Subjects:
Acetates
Acetylation
cryo-EM
Cryoelectron Microscopy
Data collection
DNA binding proteins
DNA repair
Electron microscopy
Gene expression
Genetic transcription
histone acetylation
Histone acetyltransferase
Histone Acetyltransferases - metabolism
histone modifications
Histones
Kinases
Life Sciences & Biomedicine - Other Topics
Mass spectrometry
Microscopy
Molecular weight
NuA4 protein
Nucleosomes
Nucleosomes - metabolism
Protein structure
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - metabolism
Scientific imaging
Structural Biology and Molecular Biophysics
Transcription factors
Trimers
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Summary:The NuA4 protein complex acetylates histones H4 and H2A to activate both transcription and DNA repair. We report the 3.1-Å resolution cryo-electron microscopy structure of the central hub of NuA4, which flexibly tethers the histone acetyltransferase (HAT) and Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (TINTIN) modules. The hub contains the large Tra1 subunit and a core that includes Swc4, Arp4, Act1, Eaf1, and the C-terminal region of Epl1. Eaf1 stands out as the primary scaffolding factor that interacts with the Tra1, Swc4, and Epl1 subunits and contributes the conserved HSA helix to the Arp module. Using nucleosome-binding assays, we find that the HAT module, which is anchored to the core through Epl1, recognizes H3K4me3 nucleosomes with hyperacetylated H3 tails, while the TINTIN module, anchored to the core via Eaf1, recognizes nucleosomes that have hyperacetylated H2A and H4 tails. Together with the known interaction of Tra1 with site-specific transcription factors, our data suggest a model in which Tra1 recruits NuA4 to specific genomic sites then allowing the flexible HAT and TINTIN modules to select nearby nucleosomes for acetylation.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.81400