The Nucleosome Remodeling and Deacetylase Complex Has an Asymmetric, Dynamic, and Modular Architecture.

Autor:	Low JKK; School of Life and Environmental Sciences, University of Sydney, NSW, Australia. Electronic address: jason.low@sydney.edu.au., Silva APG; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Sharifi Tabar M; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Torrado M; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Webb SR; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Parker BL; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Sana M; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Smits C; Sydney, NSW, Australia., Schmidberger JW; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Brillault L; School of Chemistry and Molecular Biosciences, University of Queensland, QLD, Australia., Jackman MJ; School of Chemistry and Molecular Biosciences, University of Queensland, QLD, Australia., Williams DC Jr; Dept of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA., Blobel GA; The Division of Hematology, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Hake SB; Institute for Genetics, FB08 Biology, Justus-Liebig-University Giessen, Giessen, Germany., Shepherd NE; School of Life and Environmental Sciences, University of Sydney, NSW, Australia., Landsberg MJ; School of Chemistry and Molecular Biosciences, University of Queensland, QLD, Australia. Electronic address: m.landsberg@uq.edu.au., Mackay JP; School of Life and Environmental Sciences, University of Sydney, NSW, Australia. Electronic address: joel.mackay@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Dec 01; Vol. 33 (9), pp. 108450.
DOI:	10.1016/j.celrep.2020.108450
Abstrakt:	The nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native mammalian NuRD complex, combining quantitative mass spectrometry, cross-linking, protein biochemistry, and electron microscopy to define the architecture of the complex. NuRD is built from a 2:2:4 (MTA, HDAC, and RBBP) deacetylase module and a 1:1:1 (MBD, GATAD2, and Chromodomain-Helicase-DNA-binding [CHD]) remodeling module, and the complex displays considerable structural dynamics. The enigmatic GATAD2 controls the asymmetry of the complex and directly recruits the CHD remodeler. The MTA-MBD interaction acts as a point of functional switching, with the transcriptional regulator PWWP2A competing with MBD for binding to the MTA-HDAC-RBBP subcomplex. Overall, our data address the long-running controversy over NuRD stoichiometry, provide imaging of the mammalian NuRD complex, and establish the biochemical mechanism by which PWWP2A can regulate NuRD composition. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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