Remodelling without a power stroke.

DNA within eukaryotic organisms is packaged into chromatin, which helps organization and compaction of the genetic material in the limited space within the nucleus. However, for efficient transcription, nucleosome positioning must be dynamically regulated, either allowing access to the transcription machinery or to block spurious gene expression [1]. Nucleosomes are inherently stable structures, with multiple contacts between DNA and the histone octamer. To perturb nucleosomes, eukaryotes have molecular machines called chromatin remodellers. These bind to DNA and the octamer core and harness the energy of ATP hydrolysis to disrupt DNA–histone contacts [2]. Swi/Snf-like chromatin remodellers slide or evict nucleosomes exposing DNA segments, which allows binding by transcription factors [2,3]. By contrast the ISWI and CHD family of remodellers slide and space nucleo somes to form ordered nucleosomal arrays that are refractory to transcription [2,3]. Nucleosomes are made up of a histone octamer core, with the DNA wrapped oneand-three-quarter turns around it. DNA enters the nucleosome through a distinct entry site and extrudes out of the exit site (Fig 1). Unlike Snf2, ISWI and CHD remodellers contain accessory DNA-binding domains, HANDSANT SLIDE, at their carboxyl termini, in addition to the conserved helicase domain [2,3]. The helicase domain of ISWI and CHD enzymes binds to nucleosomal DNA at super helical location2 (SHL2), a region that is two helical turns away from the centre of the nucleosome (dyad axis), whereas the DNAbinding domain contacts super helical location 7 (SHL7) near the DNA entry site (Fig 1). Single-molecule studies show that remodelling ensues when the helicase domain bound to SHL2, uses ATP hydrolysis to translocate DNA in 1 bp increments [4]. These steps of translocation allow 7 bp to extrude from the exit site, simultaneously resulting in a strain on the nucleosomal DNA. For movement of DNA into the nucleosome, it has been hypothesized that an ATPase-dependent power stroke generates force between the helicase and DNA-binding domains, which allows entry of 3 bp of DNA into the nucleosome and releases the strain on the DNA (Fig 1A). Subsequent exit of DNA happens in 3 bp increments that are coupled with entry of DNA of similar length. However, studies have shown that the introduction of nicks or singlestranded gaps, which work to release strain on the nucleosomal DNA, does not significantly affect remodelling [5]. Also, deleting or mutating the DNA-binding domain of these proteins only partly reduces remodelling [6]. These observations argue against a strict requirement for a power stroke.