Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex

• 成果类型: Article
• 署名作者: Yang, Zhenlin; Mameri, Amel; Cattoglio, Claudia; Lachance, Catherine; Florez Ariza, Alfredo Jose; Luo, Jie; Humbert, Jonathan; Sudarshan, Deepthi; Banerjea, Arul; Galloy, Maxime; Fradet-Turcotte, Amelie; Lambert, Jean-Philippe; Ranish, Jeff A.; Cote, Jacques; Nogales, Eva
• 署名单位: University of California System; University of California Berkeley; University of California System; University of California Berkeley; Howard Hughes Medical Institute; Laval University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Institute for Systems Biology (ISB); Laval University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9171
• DOI: 10.1126/science.adl5816
• 发表日期: 2024-08-23
• 关键词: histone variant h2a.z; cryo-em; embryonic stem; tip60 complex; RECOGNITION; transcription; acetylation; myc; architecture; deposition

摘要

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.