Molecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler
The SWR1 chromatin remodeling complex (SRCAP in humans) is recruited to +1 nucleosomes downstream of transcription start sites of eukaryotic promoters, where it exchanges histone H2A for the specialized variant H2A.Z. Here we use cryo-EM to resolve the structural basis of the SWR1 interaction with free DNA, revealing a distinct open conformation of the Swr1 ATPase that enables sliding from accessible DNA to nucleosomes. A complete structural model of the SWR1-nucleosome complex illustrates critical structure-function roles for Swc2 and Swc3 subunits in oriented nucleosome engagement by SWR1. Moreover, an extended DNA-binding a -helix within the Swc3 subunit enables sensing of nucleosome linker length and is essential for SWR1 promoter-specific recruitment and activity. The previously unresolved N-SWR1 subcomplex forms a flexible extended structure enabling multivalent recognition of acetylated histone tails by reader domains to further direct SWR1 towards the +1 nucleosome. Altogether, our findings provide a generalizable mechanism for promoter-specific targeting of chromatin and transcription complexes. Overall design: Chromatin Immunoprecipitation DNA-sequencing with exonuclease treatment (ChIP-exo) for histone variant H2A.Z and chromatin remodeler Swr1 in S. Cerevisiae with genetic modifications in the SWR1 complex