Show Notes
Shi W et al., Mechanistic insights into histone recognition and H3K14 acetylation by the NuA3 histone acetyltransferase complex - Cryo-EM structures of the yeast NuA3 complex show a composite histone tail binding cleft formed by Sas3 and Nto1 that dictates selective acetylation of H3K14. Key terms: NuA3, Sas3, Nto1, H3K14 acetylation, cryo-EM.
Study Highlights:
The six-subunit NuA3 complex was purified and shown to acetylate H3K14 preferentially on H3K4- or H3K36-trimethylated substrates. Cryo-EM maps of the apo, acetyl-CoA-bound, and acetyl-CoA plus H3 tail-bound states were determined at 3.7 Å, 3.1 Å, and 3.2 Å resolution, respectively. The H3 tail binding cleft is formed cooperatively by the catalytic Sas3 MYST domain and the Nto1 PZP region, with a hydrophobic pocket engaging H3 residues 9–12 and a network of polar contacts around Gly13–Ala15 that confer site specificity. Mutations predicted to disrupt contacts (L369R, N354A, E452Q) impair or abolish HAT activity in vitro and reduce H3K14 acetylation in yeast. Binding of acetyl-CoA induces conformational shifts in a histone-engaging loop and a CoA-engaging helix that likely position catalytic residues for transfer
Conclusion:
The structures define how cooperative recognition by Sas3 and Nto1 and local conformational changes confer high specificity for H3K14 acetylation and suggest conservation of this recognition mode in human homologs
Music:
Enjoy the music based on this article at the end of the episode.
First author:
Shi W
Journal:
Mechanistic insights into histone recognition and H3K14 acetylation by the NuA3 histone acetyltransferase complex
DOI:
10.1038/s41467-025-67049-0
Reference:
Shi W., Zhao L., Wang Y., Zhang Y., Liu S., Wang Y., Kornberg R. D., Zhang H. Mechanistic insights into histone recognition and H3K14 acetylation by the NuA3 histone acetyltransferase complex. Nat Commun (2025). https://doi.org/10.1038/s41467-025-67049-0
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-19.
QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript's coverage of NuA3 structure-function findings: complex composition, cooperative histone tail binding cleft, acetyl-CoA–induced conformational priming, substrate specificity with Gly13, mutational evidence (L369R, N354A, E452Q), recruitment marks (H3K4me3/H3K36me3), and cross-species conservation
- transcript topics: NuA3 subunit composition; Cooperative H3 tail binding cleft formed by Sas3 and Nto1; Acetyl-CoA binding and conformational priming; Substrate specificity and Gly13 determinant; Mutational effects: L369R, N354A, E452Q; Recruitment marks: H3K4me3 and H3K36me3
QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0
Metadata Audited:
- article_doi
- article_title
- article_journal
- license
Factual Items Audited:
- NuA3 is a six-subunit histone acetyltransferase complex (Sas3, Nto1, Yng1, Eaf6, Taf14, Pdp3).
- NuA3 acetylates histone H3K14 and recruitment depends on pre-existing marks H3K4me3 and H3K36me3.
- A deep histone tail binding cleft is formed cooperatively by Sas3 and Nto1, yielding site specificity for H3K14.
- Acetyl-CoA binding to Sas3 primes the complex by repositioning the histone-engaging loop and the CoA-engaging helix to facilitate tail docking.
- Gly13 preceding K14 acts as a critical determinant; G13R mutation reduces or abolishes HAT activity.
- Mutations L369R and N354A disrupt histone-tail interactions; E452Q abolishes catalytic activity.
QC result: Pass.
