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Molecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler

Affiliations
  • 1Department of Biology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: rklouder@jhu.edu.
  • 2Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 3Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
  • 4Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
  • 5Department of Chemistry, University of Konstanz, Konstanz, Germany; Department of Biology, University of Konstanz, Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
  • 6Department of Biology, University of Konstanz, Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
  • 7Department of Biology, Johns Hopkins University, Baltimore, MD, USA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: wuc@jhu.edu.

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October 2, 2024

Abstract

The SWR1 chromatin remodeling complex 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 cryoelectron microscopy (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 roles for Swc2 and Swc3 subunits in oriented nucleosome engagement by SWR1. Moreover, an extended DNA-binding α 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 toward the +1 nucleosome. Altogether, our findings provide a generalizable mechanism for promoter-specific targeting of chromatin and transcription complexes.

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