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  Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations

Farnung, L., Ochmann, M., & Cramer, P. (2020). Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations. eLife, 9: e56178. doi:10.7554/eLife.56178.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-96C6-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-96D4-1
Genre: Journal Article

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 Creators:
Farnung, L.1, Author              
Ochmann, M.1, Author              
Cramer, P.1, Author              
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1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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 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.

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Language(s): eng - English
 Dates: 2020-06-16
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.7554/eLife.56178
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Title: eLife
Source Genre: Journal
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Pages: 32 Volume / Issue: 9 Sequence Number: e56178 Start / End Page: - Identifier: -