title: The Schizosaccharomyces pombe JmjC-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains.
abstract: Eukaryotic genomes are repetitively packaged into chromatin by nucleosomes, however they are regulated by the differences between nucleosomes, which establish various chromatin states. Local chromatin cues direct the inheritance and propagation of chromatin status via self-reinforcing epigenetic mechanisms. Replication-independent histone exchange could potentially perturb chromatin status if histone exchange chaperones, such as Swr1C, loaded histone variants into wrong sites. Here we show that in Schizosaccharomyces pombe, like Saccharomyces cerevisiae, Swr1C is required for loading H2A.Z into specific sites, including the promoters of lowly expressed genes. However S. pombe Swr1C has an extra subunit, Msc1, which is a JumonjiC-domain protein of the Lid/Jarid1 family. Deletion of Msc1 did not disrupt the S. pombe Swr1C or its ability to bind and load H2A.Z into euchromatin, however H2A.Z was ectopically found in the inner centromere and in subtelomeric chromatin. Normally this subtelomeric region not only lacks H2A.Z but also shows uniformly lower levels of H3K4me2, H4K5, and K12 acetylation than euchromatin and disproportionately contains the most lowly expressed genes during vegetative growth, including many meiotic-specific genes. Genes within and adjacent to subtelomeric chromatin become overexpressed in the absence of either Msc1, Swr1, or paradoxically H2A.Z itself. We also show that H2A.Z is N-terminally acetylated before, and lysine acetylated after, loading into chromatin and that it physically associates with the Nap1 histone chaperone. However, we find a negative correlation between the genomic distributions of H2A.Z and Nap1/Hrp1/Hrp3, suggesting that the Nap1 chaperones remove H2A.Z from chromatin. These data describe H2A.Z action in S. pombe and identify a new mode of chromatin surveillance and maintenance based on negative regulation of histone variant misincorporation.
authors.affiliation: Genomics, BioInnovationsZentrum, Technische Universität Dresden, Dresden, Germany.
authors.forename: Luke
authors.initials: L
authors.lastname: Buchanan
authors.forename: Mickaël
authors.initials: M
authors.lastname: Durand-Dubief
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.forename: Cagri
authors.initials: C
authors.lastname: Sakalar
authors.forename: Brian
authors.initials: B
authors.lastname: Wilhelm
authors.forename: Annelie
authors.initials: A
authors.lastname: Strålfors
authors.forename: Anna
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Rein
authors.initials: R
authors.lastname: Aasland
authors.forename: Andrej
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
authors.forename: A
authors.initials: A
authors.lastname: Francis Stewart
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D022004:Chromosome Structures / Q000378:metabolism*; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D021122:Protein Subunits; D040901:Proteomics / Q000379:methods*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D006657:Histones; D018832:Molecular Chaperones; C486643:Msc1 protein, S pombe; C530617:Nap1 protein, S pombe; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C077020:histone H2A.F-Z; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae; D008239:Lysine