title: H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast.
abstract: The histone variant H2A.Z is a universal mark of gene promoters, enhancers, and regulatory elements in eukaryotic chromatin. The chromatin remodeler SWR1 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement reaction, evicting histone H2A-H2B from the canonical nucleosome and depositing the H2A.Z-H2B dimer. Binding of both substrates, the canonical nucleosome and the H2A.Z-H2B dimer, is essential for activation of SWR1. We found that SWR1 primarily recognizes key residues within the α2 helix in the histone-fold of nucleosomal histone H2A, a region not previously known to influence remodeler activity. Moreover, SWR1 interacts preferentially with nucleosomal DNA at superhelix location 2 on the nucleosome face distal to its linker-binding site. Our findings provide new molecular insights on recognition of the canonical nucleosome by a chromatin remodeler and have implications for ATP-driven mechanisms of histone eviction and deposition.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Anand
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Gaku
authors.initials: G
authors.lastname: Mizuguchi
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Debbie
authors.initials: D
authors.lastname: Wei
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Carl
authors.initials: C
authors.lastname: Wu
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae
keywords: H2A.Z; S. cerevisiae; biochemistry; chromatin remodeler; chromosomes; genes; nucleosome