Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes

Nucleosome-remodelling complexes can slide or eject histones, or incorporate histone variants, but they share an ATPase–translocase 'motor' and a common DNA translocation mechanism. In a unifying 'hourglass' model of remodeller function, the different remodeller subfamilies use different modules for targeting to nucleosomes but converge on a DNA translocation mechanism and then diverge again to achieve various outcomes. Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase–translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation. We propose the 'hourglass' model of remodeller function, in which each remodeller subfamily utilizes diverse specialized proteins and protein domains to assist in nucleosome targeting or to differentially detect nucleosome epitopes. These modules converge to regulate a common DNA translocation mechanism, to inform the conserved ATPase 'motor' on whether and how to apply DNA translocation, which together achieve the various outcomes of chromatin remodelling: nucleosome assembly, chromatin access and nucleosome editing.