Reference: Hughes AL, et al. (2025) Structural characterisation of chromatin remodelling intermediates supports linker DNA dependent product inhibition as a mechanism for nucleosome spacing. Elife 14

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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.

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Journal Article
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Hughes AL, Sundaramoorthy R, Owen-Hughes T
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