title: Maintenance of heterochromatin boundary and nucleosome composition at promoters by the Asf1 histone chaperone and SWR1-C chromatin remodeler in Saccharomyces cerevisiae.
abstract: Chromatin remodeling complexes cooperate to regulate gene promoters and to define chromatin neighborhoods. Here, we identified genetic and functional connections between two silencing-related chromatin factors in the maintenance of native heterochromatic structures and nucleosome composition at promoters. Building on a previously reported link between the histone chaperone Asf1 and the Yaf9 subunit of the SWR1-C chromatin remodeler, we found that ASF1 broadly interacted with genes encoding for SWR1-C subunits. Asf1 and Yaf9 were required for maintaining expression of heterochromatin-proximal genes and they worked cooperatively to prevent repression of telomere-proximal genes by limiting the spread of SIR complexes into nearby regions. Genome-wide Sir2 profiling, however, revealed that the cooperative heterochromatin regulation of Asf1 and SWR1-C occurred only on a subset of yeast telomeres. Extensive analyses demonstrated that formation of aberrant heterochromatin structures in the absence of ASF1 and YAF9 was not causal for the pronounced growth and transcriptional defects in cells lacking both these factors. Instead, genetic and molecular analysis revealed that H3K56 acetylation was required for efficient deposition of H2A.Z at subtelomeric and euchromatic gene promoters, pointing to a role for Asf1-dependent H3K56 acetylation in SWR1-C biology.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
authors.forename: Phoebe Y T
authors.initials: PY
authors.lastname: Lu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kobor
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D015966:Gene Expression Regulation, Fungal; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D016615:Telomere / Q000235:genetics
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D006570:Heterochromatin; D006657:Histones; C493530:Htz1 protein, S cerevisiae; D018832:Molecular Chaperones; D009707:Nucleosomes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae
keywords: Asf1 histone chaperone; H2A.Z histone variant; heterochromatin spread; transcription