Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32543371.
- Also identified by DOI 10.7554/eLife.56178 and PMC identifier 7338049.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Homo sapiens</i> 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.
Medical subject headings
- Adenylyl Imidodiphosphate
- Chromatin Assembly and Disassembly
- Mi-2 Nucleosome Remodeling and Deacetylase Complex
- Mutation
- Nucleosomes