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-Structure paper
Title | Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations. |
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Journal, issue, pages | Elife, Vol. 9, Year 2020 |
Publish date | Jun 16, 2020 |
Authors | Lucas Farnung / Moritz Ochmann / Patrick Cramer / |
PubMed 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 ...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 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. |
External links | Elife / PubMed:32543371 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.1 - 4.0 Å |
Structure data | EMDB-10058, PDB-6ryr: EMDB-10059, PDB-6ryu: |
Chemicals | ChemComp-ANP: ChemComp-MG: ChemComp-ZN: |
Source |
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Keywords | TRANSCRIPTION / Complex / ATPase / chromatin / nucleosome / CHD family |