Journal article

Publication year: 2020

Pages: 108450-

Journal: Cell Reports

Volume number: 33

Issue number: 9

ISSN: 2211-1247

Open access status: Gold

DOI Link: https://doi.org/10.1016/j.celrep.2020.108450

Publisher: Cell Press

Abstract: 
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.

Harvard Citation style: Low, J., Silva, A., Tabar, M., Torrado, M., Webb, S., Parker, B., et al. (2020) The Nucleosome Remodeling and Deacetylase Complex Has an Asymmetric, Dynamic, and Modular Architecture, Cell Reports, 33(9), p. 108450. https://doi.org/10.1016/j.celrep.2020.108450

APA Citation style: Low, J., Silva, A., Tabar, M., Torrado, M., Webb, S., Parker, B., Sana, M., Smits, C., Schmidberger, J., Brillault, L., Jackman, M., Williams, D., Blobel, G., Hake, S., Shepherd, N., Landsberg, M., & Mackay, J. (2020). The Nucleosome Remodeling and Deacetylase Complex Has an Asymmetric, Dynamic, and Modular Architecture. Cell Reports. 33(9), 108450. https://doi.org/10.1016/j.celrep.2020.108450