Structural characterisation of chromatin remodelling intermediates supports linker DNA-dependent product inhibition as a mechanism for nucleosome spacing
Year: 2025
Type: article
Abstract: Chd1 chromatin remodelling enzyme associates with nucleosomes oriented towards the longer linker (Sundaramoorthy et al., 2018) (1). Here, we report a series of structures of Chd1 bound to nucleosomes during ongoing ATP-dependent repositioning. Combining these with biochemical experiments and existing literature, we propose a model in which Chd1 first associates oriented to sample putative entry DNA. In an ATP-dependent reaction, the enzyme then redistributes to the opposite side of the nucleosome, where it subsequently adopts a conformation productive for DNA translocation. Once this active complex extends the nascent exit linker to approximately 15 bp, it is sensed by the Chd1 DNA binding domain, resulting in conversion to a product-inhibited state. These observations provide a mechanistic basis for the action of a molecular ruler element in nucleosome spacing.
Source: eLife
DOI: 10.7554/elife.52513
Institution: University of Dundee
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Theory of Gamma-Ray Bursts and relativistic collisionless shocks, Supporting transnational mobility within the European life sciences by cofunding of the EMBO Fellowship Programme, G562890076, Wellcome Trust Technology Platform, G7999040392, G8601990786, Establishment of Cryo-EM screening facility at University of Dundee, Structure and function of chromatin remodelling ATPase's and their dysfunction in in human disease.
OpenAlex ID: W7117149954