Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations
- Max Planck Institute for Biophysical Chemistry, Germany
Abstract
Chromatin remodelling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.
Data availability
The cryo-EM reconstructions and final models were deposited with the Electron Microscopy Data Base (accession codes EMD-10058 and EMD-10059) and with the Protein Data Bank (accession code 6RYR and 6RYU). The raw image data and corresponding WARP sessions have been deposited to EMPIAR (EMPIAR-10411).
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Nucleosome-CHD4 complex structure (single CHD4 copy)Electron Microscopy Data Base, EMDB-10058.
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Nucleosome-CHD4 complex structure (two CHD4 copies)Electron Microscopy Data Base, EMDB-10059.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SFB1064)
- Patrick Cramer
Deutsche Forschungsgemeinschaft (SFB860)
- Patrick Cramer
European Research Council (693023)
- Patrick Cramer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Farnung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations
eLife 9:e56178.
https://doi.org/10.7554/eLife.56178
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