Nucleosome-free Region Dominates Histone Acetylation in Targeting SWR1 to Promoters for H2A.Z Replacement

Abstract

Summary The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to eukaryotic regulatory DNA. While the multi-subunit chromatin remodeler SWR1 is known to catalyze ATP-dependent deposition of H2A.Z, the mechanism of SWR1 recruitment to S. cerevisiae promoters has been unclear. A sensitive assay for competitive binding of di-nucleosome substrates revealed that SWR1 preferentially binds long nucleosome-free DNA and the adjoining nucleosome core particle, allowing discrimination of gene promoters over gene bodies. Analysis of mutants indicates that the conserved Swc2/YL1 subunit and the ATPase domain of Swr1 are mainly responsible for binding to substrate. SWR1 binding is enhanced on nucleosomes acetylated by the NuA4 histone acetyltransferase, but recognition of nucleosome-free and nucleosomal DNA is dominant over interaction with acetylated histones. Such hierarchical cooperation between DNA and histone signals expands the dynamic range of genetic switches, unifying classical gene regulation by DNA-binding factors with ATP-dependent nucleosome remodeling and post-translational histone modifications.

Regulation of microRNA-mediated developmental changes by the SWR1 chromatin remodeling complex in Arabidopsis thaliana

“…The ATP-dependent SWR1 chromatin remodeling complex (SWR1-C) catalyzes the replacement of H2A-H2B dimers with H2A.Z-H2B dimers in nucleosome structures, thus producing variant nucleosomes with dynamic properties (Mizuguchi et al, 2004;Luk et al, 2010). The H2A.Z-containing nucleosomes preferentially localize around transcription start sites and in the vicinity of the genes where SWR1-C is recruited, through the direct DNA binding of the SWR1 and SWC2, components of the complex (Raisner et al, 2005;Deal et al, 2007;Zilberman et al, 2008;Jin et al, 2009;Ranjan et al, 2013;Yen et al, 2013).…”

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

“…The Swr1 complex binds to acetylated histones in general to preferentially deposit H2A.Z at acetylated regions of the genome [55]. However, recent studies by Ranjan et al showed that recognition of a nucleosome-free region by the Swr1 complex was more efficient for its targeting to DNA than recognition of acetylated chromatin [56]. The link between histone acetylation and SWR1 targeting may also depend on the site of acetylation since hyperacetylation of H3K56 was found to antagonize binding of Swr1 complex and prevent H2A.Z deposition in yeast [57].…”

Maintenance of Heterochromatin Boundary and Nucleosome Composition at Promoters by the Asf1 Histone Chaperone and SWR1-C Chromatin Remodeler in Saccharomyces cerevisiae

“…Despite these strong correlations, the causal role of H2A.Z for gene expression is more nebulous as genome-wide expression studies found that loss of H2A.Z affects only a minority of genes in yeast (Meneghini et al 2003). In recent years, many studies have suggested that rather than affecting steady-state gene expression, H2A.Z may facilitate the induction of genes in response to changing environments (Adam et al 2001;Larochelle and Gaudreau 2003;Lemieux et al 2008;Halley et al 2010).H2A.Z is deposited into chromatin by SWR1-C, an ATPasedependent chromatin remodeling complex that recognizes the NFR and exchanges H2A-H2B dimers with H2A.Z-H2B dimers at the two flanking nucleosomes (Krogan et al 2003;Kobor et al 2004;Mizuguchi et al 2004;Ranjan et al 2013). Illustrative of the cross-talk between chromatin remodelers, SWR1-C and the NuA4 histone acetyltransferase (HAT) have interconnected activities converging on H2A.Z chromatin neighborhoods.…”

“…Illustrative of the cross-talk between chromatin remodelers, SWR1-C and the NuA4 histone acetyltransferase (HAT) have interconnected activities converging on H2A.Z chromatin neighborhoods. Acetylation of H4 lysine residues by NuA4 promotes the recruitment of SWR1-C for H2A.Z deposition, and subsequent acetylation of newly incorporated H2A.Z by NuA4 is required for gene activation and heterochromatin formation (Babiarz et al 2006;Durant and Pugh 2007;Altaf et al 2010;Ranjan et al 2013). The interplay between SWR1-C and NuA4 likely involves a module of four subunits that is shared between the two complexes (Lu et al 2009).…”

“…H2A.Z is deposited into chromatin by SWR1-C, an ATPasedependent chromatin remodeling complex that recognizes the NFR and exchanges H2A-H2B dimers with H2A.Z-H2B dimers at the two flanking nucleosomes (Krogan et al 2003;Kobor et al 2004;Mizuguchi et al 2004;Ranjan et al 2013). Illustrative of the cross-talk between chromatin remodelers, SWR1-C and the NuA4 histone acetyltransferase (HAT) have interconnected activities converging on H2A.Z chromatin neighborhoods.…”