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

The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to eukaryotic regulatory DNA. Whereas the multisubunit 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 dinucleosome 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 adenosine triphosphatase 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 posttranslational histone modifications. [Display omitted] •SWR1 recognizes universal nucleosome-free architecture at gene promoters•DNA binding is dominant over histone acetylation for SWR1 targeting•Swc2 subunit is responsible for DNA recognition in addition to H2A.Z binding•NFR length correlates with SWR1 occupancy in vivo The chromatin-remodeling complex SWR1 recognizes both the nucleosome-free region and histone acetylation at gene promoters. Such hierarchical cooperation between DNA and histone signals unifies classical mechanisms of gene control by DNA-binding transcription factors with ATP-dependent nucleosome remodeling and posttranslational histone modifications.