| Title: |
Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex. |
| Authors: |
Yang, Zhenlin; Mameri, Amel; Cattoglio, Claudia; Lachance, Catherine; Florez Ariza, Alfredo Jose; Luo, Jie; Humbert, Jonathan; Sudarshan, Deepthi; Banerjea, Arul; Galloy, Maxime; Fradet-Turcotte, Amélie; Lambert, Jean-Philippe; Ranish, Jeff A; Côté, Jacques; Nogales, Eva |
| Source: |
Articles, Abstracts, and Reports |
| Publisher Information: |
Providence Digital Commons |
| Publication Year: |
2024 |
| Collection: |
Providence St. Joseph Health Digital Commons |
| Subject Terms: |
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; Systems Biology |
| Description: |
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. |
| Document Type: |
text |
| Language: |
unknown |
| Relation: |
https://digitalcommons.providence.org/publications/9091; https://pubmed.ncbi.nlm.nih.gov/39088653/ |
| DOI: |
10.1126/science.adl5816 |
| Availability: |
https://digitalcommons.providence.org/publications/9091; https://doi.org/10.1126/science.adl5816; https://pubmed.ncbi.nlm.nih.gov/39088653/ |
| Accession Number: |
edsbas.E47D2874 |
| Database: |
BASE |