The Chromodomain Protein Swi6: A Key Component at Fission Yeast Centromeres

Ekwall, Karl; Javerzat, Jean‐Paul; Lorentz, Axel; Schmidt, Henning; Cranston, Gwen; Allshire, Robin C.

doi:10.1126/science.7660126

Cited by 290 publications

(236 citation statements)

References 23 publications

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“…We also employed fluorescence microscopy to determine the effect of epe1 genotype on nuclear localization of Swi6-ECFP ( Figure 1B). Consistent with previous observations (Ekwall et al 1995), Swi6-ECFP was localized in epe1 1 cells (AP938) to a small number of distinct foci at heterochromatic domains. Fluorescent foci were also visible in cells of an epe1Tura4 1 mutant (AP940) and in cells that overexpress epe1 1 (AP944).…”

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confidence: 79%

Interaction of Epe1 With the Heterochromatin Assembly Pathway inSchizosaccharomyces pombe

et al. 2007

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Epe1 is a JmjC domain protein that antagonizes heterochromatization in Schizosaccharomyces pombe. Related JmjC domain proteins catalyze a histone demethylation reaction that depends on Fe(II) and a-ketoglutarate. However, no detectable demethylase activity is associated with Epe1, and its JmjC domain lacks conservation of Fe(II)-binding residues. We report that Swi6 recruits Epe1 to heterochromatin and that overexpression of epe1 1 , like mutations in silencing genes or overexpression of swi6 1 , upregulates expression of certain genes. A significant overlap was observed between the lists of genes that are upregulated by overexpression of epe1 1 and those that are upregulated by mutations in histone deacetylase genes. However, most of the common genes are not regulated by Clr4 histone methyltransferase. This suggests that Epe1 interacts with the heterochromatin assembly pathway at the stage of histone deacetylation. Mutational inactivation of Epe1 downregulates $12% of S. pombe genes, and the list of these genes overlaps significantly with the lists of genes that are upregulated by mutations in silencing genes and genes that are hyperacetylated at their promoter regions in clr6-1 mutants. We propose that an interplay between the repressive HDACs activity and Epe1 helps to regulate gene expression in S. pombe.

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confidence: 79%

Interaction of Epe1 With the Heterochromatin Assembly Pathway inSchizosaccharomyces pombe

et al. 2007

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“…swi2Δ, Swi2-myc, and abp1Δ have been described previously (18,41). Mutant swi6 strains used in this study contain the missense swi6-115 (W269R) allele that causes severe reduction in Swi6 protein levels (48).…”

Section: Methodsmentioning

confidence: 99%

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination

Matsuda

Sugioka-Sugiyama

Mizuguchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Schizosaccharomyces pombe cells switch mating type by replacing genetic information at the expressed mat1 locus with sequences copied from mat2-P or mat3-M silent donor loci. The choice of donor locus is dictated by cell type, such that mat2 is the preferred donor in M cells and mat3 is the preferred donor in P cells. Donor choice involves a recombination-promoting complex (RPC) containing Swi2 and Swi5. In P cells, the RPC localizes to a specific DNA element located adjacent to mat3, but in M cells it spreads across the silent mating-type region, including mat2-P. This differential distribution of the RPC regulates nonrandom choice of donors. However, celltype-specific differences in RPC localization are not understood. Here we show that the mat1-M-encoded factor Mc, which shares structural and functional similarities with the male sex-determining factor SRY, is highly enriched at the swi2 and swi5 loci and promotes elevated levels of RPC components. Loss of Mc reduces Swi2 and Swi5 to levels comparable to those in P cells and disrupts RPC spreading across the mat2/3 region. Mc also localizes to loci expressed preferentially in M cells and to retrotransposon LTRs. We demonstrate that Mc localization at LTRs and at swi2 requires Abp1, a homolog of transposon-derived CENP-B protein and that loss of Abp1 impairs Swi2 protein expression and the donor choice mechanism. These results suggest that Mc modulates levels of recombination factors, which is important for mating-type donor selection and for the biased gene conversion observed during meiosis, where M cells serve as preferential donors of genetic information. (1) and mating-type switching in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe (2-5). In these distantly related yeast species, cells alternate between two distinct mating-type alleles by copying genetic information from one of the two silent donor loci to the active mating-type locus via highly orchestrated recombination processes (6-8).The mating-type region of S. pombe contains three linked locimat1, mat2, and mat3-located on chromosome 2. In wild-type homothallic strains, designated h 90 , mat2 is located ∼17 kb centromere-distal to mat1, whereas mat3 is separated from mat2 by an 11-kb interval ( Fig. 1) (8, 9). The mating type of a haploid cell is determined by the presence of P or M information at mat1 (8). Each allele consists of two divergently transcribed genes (10). mat1-P contains the Pc and Pi genes, and mat1-M contains the Mc and Mi genes. mat2 and mat3 contain the same genetic information as mat1-P and mat1-M, respectively, but are maintained in a silent state. These silent mating-type cassettes are embedded in a 20-kb heterochromatin domain surrounded by inverted repeat (IR-R and IR-

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“…Immunofluorescence studies were performed as described previously (Ahmed et al 2004) with TAT-1 antibody to a-tubulin (a kind gift of Keith Gull) and DAPI staining to visualize nuclei. For determining the percentage of cells with lagging chromosomes, cells were grown at 18°and cells with elongated anaphase spindles as visualized with TAT-1 antibody were counted (Ekwall et al 1995). The number of cells in anaphase with more than two DAPI staining spots were counted as having lagging chromosomes.…”

Section: Methodsmentioning

confidence: 99%

Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability inSchizosaccharomyces pombe

Ahmed¹,

Dul²,

Qiu

et al. 2007

Genetics

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As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage.

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The Chromodomain Protein Swi6: A Key Component at Fission Yeast Centromeres

Cited by 290 publications

References 23 publications

Interaction of Epe1 With the Heterochromatin Assembly Pathway inSchizosaccharomyces pombe

Interaction of Epe1 With the Heterochromatin Assembly Pathway inSchizosaccharomyces pombe

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination

Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability inSchizosaccharomyces pombe

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