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PreprintCited by 22Genomics and Chromatin DynamicsChromatin Remodeling and CancerNuclear Structure and Function

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Structure and Flexibility of the Yeast NuA4 Histone Acetyltransferase Complex

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Zukin, Stefan A., Marunde, Matthew R., Popova, Irina K., Nogales, Eva, Patel, Avinash B.·2022·eLife
DOI 10.1101/2022.06.24.497536PMC PMC9643008

Preprint — published as 10.7554/elife.81400 · Paper page

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Abstract

The NuA4 protein complex acetylates histones H4 and H2A to activate both transcription and DNA repair. We report the 3.0 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, Sw4 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.

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Metadata

Authors
Zukin, S. A., Marunde, M. R., Popova, I. K., Nogales, E., & Patel, A. B.
Affiliations
  • University of California, Berkeley (US)
  • EpiCypher (United States) (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Nogales, Eva
  • Patel, Avinash B.
ORCID
Venue
eLife
Publisher
openRxiv
Published
2022-06-25
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.1101/2022.06.24.497536
PMC
PMC9643008
OpenAlex
W4306871076
Cited by
22
References
1
Citations by year
2025: 6 · 2024: 9 · 2023: 6 · 2022: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, public-domain)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of General Medical Sciences (R44GM117683, T32GM008295, R44GM116584, R35GM127018)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
histone H4 acetylation, histone H3K4me3, Tra1, Arp4, nucleosome recognition, nucleosome acetylation, transcriptional activation, DNA repair, Saccharomyces cerevisiae, protein complex structure, protein flexibility
MeSH terms
Acetylation, Nucleosomes, Saccharomyces cerevisiae, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins, Histone Acetyltransferases

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