Structure and flexibility of the yeast NuA4 histone acetyltransferase complex
Stefan A Zukin,
Matthew R Marunde,
Irina K Popova,
Katarzyna M Soczek,
Eva Nogales,
Avinash B Patel
Affiliations
Stefan A Zukin
College of Chemistry, University of California, Berkeley, Berkeley, United States
Matthew R Marunde
EpiCypher, Inc, Research Triangle Park, Durham, United States
Irina K Popova
EpiCypher, Inc, Research Triangle Park, Durham, United States
Katarzyna M Soczek
California Institute for Quantitative Biology, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cellular Biology, University of California, Berkeley, United States; Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States
California Institute for Quantitative Biology, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cellular Biology, University of California, Berkeley, United States; Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
California Institute for Quantitative Biology, University of California, Berkeley, Berkeley, United States; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States; Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States
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.
