ACF catalyses chromatosome movements in chromatin fibres

Abstract

Nucleosome-remodelling factors containing the ATPase ISWI, such as ACF, render DNA in chromatin accessible by promoting the sliding of histone octamers. Although the ATP-dependent repositioning of mononucleosomes is readily observable in vitro, it is unclear to which extent nucleosomes can be moved in physiological chromatin, where neighbouring nucleosomes, linker histones and the folding of the nucleosomal array restrict mobility. We assembled arrays consisting of 12 nucleosomes or 12 chromatosomes (nucleosomes plus linker histone) from defined components and subjected them to remodelling by ACF or the ATPase CHD1. Both factors increased the access to DNA in nucleosome arrays. ACF, but not CHD1, catalysed profound movements of nucleosomes throughout the array, suggesting different remodelling mechanisms. Linker histones inhibited remodelling by CHD1. Surprisingly, ACF catalysed significant repositioning of entire chromatosomes in chromatin containing saturating levels of linker histone H1. H1 inhibited the ATP-dependent generation of DNA accessibility by only about 50%. This first demonstration of catalysed chromatosome movements suggests that the bulk of interphase euchromatin may be rendered dynamic by dedicated nucleosome-remodelling factors.

Developmental role for ACF1-containing nucleosome remodellers in chromatin organisation

“…ACF consists only of ISWI and ACF1, whereas CHRAC additionally contains two small histone-fold subunits (Eberharter et al, 2001;Ito et al, 1997). In vitro, ACF can promote the assembly of regular arrays of nucleosomes or chromatosomes (Lusser et al, 2005), and can catalyse the movement of nucleosomes and chromatosomes in arrays (Eberharter et al, 2004;Maier et al, 2008). Biochemically, CHRAC and ACF have very similar properties (Hartlepp et al, 2005).…”

ATP-dependent chromatosome remodeling

“…We found that ACF or its ATPase ISWI alone were able to significantly increase the access to DNA packaged in these arrays, even if they were saturated with linker histones H1 or H5 (Maier et al, 2007). Moreover, ACF catalyzed the repositioning of entire chromatosomes within these arrays (Figure 1d,g).…”

“…In our assay, linker histones almost entirely inhibited the remodeling activity of CHD1, whereas ACF remained surprisingly active (Maier et al, 2007). Because the presence of H1 affects both chromatin assembly and remodeling activities of these enzymes in similar ways, the two processes might be mechanistically linked.…”

“…Modeling the structure of the globular domain of H5 onto the nucleosome has revealed that unlike H1, H5 has the propensity to form dimers when bound to chromatin, which might contribute to the observed enhanced condensation (Fan and Roberts, 2006). In vitro, H5 inhibits chromatin remodeling by ACF to a larger degree than H1, but not entirely (Maier et al, 2007).…”

Soft skills turned into hard facts: nucleosome remodelling at developmental switches

“…Nucleosome remodelling factors differ in their ability to remodel nucleosomes in the presence of the linker histone. Those machineries, such as the ISWI-containing ACF complex (Maier et al, 2008b), that are able to move nucleosomes together with associated H1 may be better called 'chromatin remodelling factors' (reviewed in Maier et al, 2008a). In this study we discuss how chromatin remodelling factors can affect the incorporation of linker histones during development, again using the Drosophila paradigm as an example.…”