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

Key Points The dynamic regulation of chromatin involves four subfamilies of ATP-dependent nucleosome-remodelling complexes: imitation switch (ISWI), chromodomain helicase DNA-binding (CHD), switch/sucrose non-fermentable (SWI/SNF) and INO80. Each subfamily is specialized to preferentially achieve particular chromatin outcomes: assembly, access or editing. Diversity in the protein composition of remodellers enables their specific interaction with particular transcription activators, repressors and histone modifications, which together specify targeting. Although diverse in protein composition, all remodellers have a similar ATPase 'motor' that translocates DNA from a common location within the nucleosome, which breaks histone–DNA contacts. The diverse specialized proteins and domains in each remodeller subfamily are also involved in detecting nucleosome epitopes, which differentially regulate the conserved ATPase–translocase motor to achieve the various chromatin-remodelling outcomes. We propose an 'hourglass' model of chromatin remodelling that involves convergence on a DNA translocation mechanism, which is preceded and followed by remodeller diversity, in terms of differential remodeller targeting and remodelling outcomes, respectively. Remodellers are emerging as 'smart' machines that are informed about whether or how to utilize DNA translocation to conduct chromatin remodelling. 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