Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.
Publication Title
Science
Document Type
Article
Publication Date
8-23-2024
Keywords
Humans; Acetylation; Adaptor Proteins, Signal Transducing; Chromatin Assembly and Disassembly; Cryoelectron Microscopy; DNA-Binding Proteins; Histones; Lysine Acetyltransferase 5; Nuclear Proteins; Nucleosomes; Protein Domains; Transcription Factors
Abstract
The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4, H2A, and H2A.Z to regulate gene expression and maintain genome stability. Our cryo-electron microscopy studies show that, within the NuA4/TIP60 complex, the E1A binding protein P400 (EP400) subunit serves as a scaffold holding the different functional modules in specific positions, creating a distinct arrangement of the actin-related protein (ARP) module. EP400 interacts with the transformation/transcription domain-associated protein (TRRAP) subunit by using a footprint that overlaps with that of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
Specialty/Research Institute
Institute for Systems Biology
DOI
10.1126/science.adl5816
