Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex-Reference-Cited by-同舟云学术

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

Published:2024-08-23 Issue:6711 Volume:385 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Yang Zhenlin¹²^ORCID,Mameri Amel³^ORCID,Cattoglio Claudia²⁴^ORCID,Lachance Catherine³^ORCID,Florez Ariza Alfredo Jose¹⁵^ORCID,Luo Jie⁶^ORCID,Humbert Jonathan³^ORCID,Sudarshan Deepthi³^ORCID,Banerjea Arul⁴^ORCID,Galloy Maxime³^ORCID,Fradet-Turcotte Amélie³^ORCID,Lambert Jean-Philippe⁷^ORCID,Ranish Jeff A.⁶^ORCID,Côté Jacques³^ORCID,Nogales Eva¹²⁴⁸^ORCID

Affiliation:

1. California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.

2. Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.

3. St-Patrick Research Group in Basic Oncology, Oncology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.

4. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

5. Biophysics Graduate Group, University of California, Berkeley, CA, USA.

6. Institute for Systems Biology, Seattle, WA, USA.

7. Endocrinology Division of the CHU de Québec-Université Laval Research Center, Laval University Cancer Research Center, Quebec City, QC, Canada.

8. Molecular Biophysics and Integrative Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adl5816

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