title: Swc2 is a widely conserved H2AZ-binding module essential for ATP-dependent histone exchange.
abstract: The histone variant H2AZ is incorporated preferentially at specific locations in chromatin to modulate chromosome functions. In Saccharomyces cerevisiae, deposition of histone H2AZ is mediated by the multiprotein SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Here, we define interactions between SWR1 components and H2AZ, revealing a link between the ATPase domain of Swr1 and three subunits required for the binding of H2AZ. We discovered that Swc2 binds directly to and is essential for transfer of H2AZ. Swc6 and Arp6 are necessary for the association of Swc2 and for nucleosome binding, whereas other subunits, Swc5 and Yaf9, are required for H2AZ transfer but neither H2AZ nor nucleosome binding. Finally, the C-terminal alpha-helix of H2AZ is crucial for its recognition by SWR1. These findings provide insight on the initial events of histone exchange.
authors.affiliation: Laboratory of Molecular Cell Biology, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Building 37, Room 6068, Bethesda, Maryland 20892-4255, USA.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Wu
authors.forename: Samar
authors.initials: S
authors.lastname: Alami
authors.forename: Edward
authors.initials: E
authors.lastname: Luk
authors.forename: Chwen-Huey
authors.initials: CH
authors.lastname: Wu
authors.forename: Subhojit
authors.initials: S
authors.lastname: Sen
authors.forename: Gaku
authors.initials: G
authors.lastname: Mizuguchi
authors.forename: Debbie
authors.initials: D
authors.lastname: Wei
authors.forename: Carl
authors.initials: C
authors.lastname: Wu
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; C493530:Htz1 protein, S cerevisiae; D009707:Nucleosomes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae