Structure and flexibility of the yeast NuA4 histone acetyltransferase complex
Abstract
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 HAT and 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 suggests 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.
Data availability
The cryo-EM maps and coordinate models have been deposited in the Electron Microscopy Data Bank with the accession codes EMD-28575 (NuA4 full), EMD-28563 (NuA4 core), EMD-28565 (NuA4 Tra1-FATKIN), EMD-28566 (Tra1-HEAT), EMD-28568 (Tra1-HEAT-top), EMD-28569 (Tra1-HEAT-middle), EMD-28567 (Tra1-HEAT-bottom) and in the Protein Data Bank with the accession codes PDB-8ESC (NuA4). Plasmids for HAT and TINTIN expression have been made available through Addgene (Catalog #193325 (S.c. NuA4 HAT) and #193326 (S.c NuA4 TINTIN)).
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Structure of the Yeast NuA4 Histone Acetyltransferase ComplexRCSB Protein Data Bank, 8ESC.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28575.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28563.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28565.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28566.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28568.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28569.
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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase ComplexElectron Microscopy Data Bank, EMD-28567.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R35-GM127018)
- Stefan A Zukin
- Eva Nogales
- Avinash B Patel
National Institute of General Medical Sciences (R44GM117683)
- Matthew R Marunde
- Irina K Popova
National Institute of General Medical Sciences (R44GM116584)
- Matthew R Marunde
- Irina K Popova
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Volker Dötsch, Goethe University, Germany
Version history
- Preprint posted: June 25, 2022 (view preprint)
- Received: June 25, 2022
- Accepted: October 17, 2022
- Accepted Manuscript published: October 20, 2022 (version 1)
- Version of Record published: November 8, 2022 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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