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XB-ART-57826
Elife 2020 Jun 16;9. doi: 10.7554/eLife.56178.
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Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations.

Farnung L , Ochmann M , Cramer P .


Abstract
Chromatin remodeling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodeling 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 remodeling. 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.

PubMed ID: 32543371
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: chd1 chd2 chd3 chd4 chd5 chd6 chd7 chd8 h2ac21 h2bc21 pnp smarca4 vwa1
GO keywords: chromatin remodeling [+]

OMIMs: SIFRIM-HITZ-WEISS SYNDROME; SIHIWES

Article Images: [+] show captions
References [+] :
Afonine, Real-space refinement in PHENIX for cryo-EM and crystallography. 2018, Pubmed