# Mechanistic insights into histone recognition and H3K14 acetylation by the NuA3 histone acetyltransferase complex

## TL;DR

This study reveals how the NuA3 complex recognizes histones and acetylates H3K14 using cryo-EM structures.

## Contribution

The study provides the first structural insights into the NuA3 complex's histone recognition and acetylation mechanism.

## Key findings

- The NuA3 complex's histone tail-binding cleft is formed by Sas3 and Nto1 subunits.
- A hydrophobic region and polar interactions contribute to H3K14 acetylation specificity.
- Cryo-EM structures show how NuA3 binds acetyl-CoA and the histone H3 tail.

## Abstract

The NuA3 histone acetyltransferase complex in budding yeast, composed of six subunits, specifically acetylates lysine 14 on histone H3 (H3K14), thereby regulating various biological processes. Despite its importance, the structural basis and mechanism underlying histone tail recognition and substrate specificity of the NuA3 complex have remained elusive. Here we report cryo-electron microscopy structures of the NuA3 complex in its apo form, bound to acetyl-coenzyme A (acetyl-CoA), and in a complex with both the histone H3 tail and acetyl-CoA. Our structure shows that the histone tail-binding cleft of NuA3 is formed cooperatively by two subunits, the catalytic subunit Sas3 and the non-catalytic subunit Nto1. A hydrophobic part of the cleft engages the region preceding H3K14 (residues 9-12), while a network of polar interactions between the cleft and the backbone of H3 residues 12-15, particularly involving Gly13, contributes to substrate specificity.

The yeast NuA3 histone acetyltransferase complex catalyzes acetylation of histone H3 at lysine 14 (H3K14). Here, the authors present the cryo-EM structures of NuA3 in the apo state and bound to acetylcoenzyme A and the histone tail, illustrating the molecular basis of histone recognition and the mechanism of H3K14 acetylation.