Structural characterisation of chromatin remodelling intermediates supports linker DNA dependent product inhibition as a mechanism for nucleosome spacing
- University of Dundee, United Kingdom
Abstract
Previously we showed that Saccharomyces cerevisiae 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 nascent exit linker to approximately 15bp, 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.
Data availability
Cryo-EM density maps have been deposited in the EM Data Resource under accession codes EMD-53596 (nucleosome), EMD-53590 (Chd1-nucleosome complex I), EMD-53597 (Chd1-nucleosome complex II), EMD-53595 (Chd1-nucleosome complex III). The atomic coordinates have been deposited in the Protein Data Bank under accession codes PDB 9R5W (Nucleosome), PDB 9R5K (Chd1-complex I), and PDB 9R5S (Chd1-complex III).All other data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Ramasubramanian Sundaramoorthy
Funding
Medical Research Council (MR/S021647/1)
- Ramasubramanian Sundaramoorthy
- Tom Owen-Hughes
Wellcome Trust (097945)
- Ramasubramanian Sundaramoorthy
- Tom Owen-Hughes
European Molecular Biology Organization (ALTF 380-2015)
- Amanda L Hughes
Wellcome Trust (223816/Z/21/Z)
- Tom Owen-Hughes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2025, Hughes et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Structural characterisation of chromatin remodelling intermediates supports linker DNA dependent product inhibition as a mechanism for nucleosome spacing
eLife 14:e52513.
https://doi.org/10.7554/eLife.52513
