Cell-cycle control of the establishment of mating-type silencing in <i>S. cerevisiae</i>

Lau, Anna F.; Blitzblau, Hannah G.; Bell, Stephen P.

doi:10.1101/gad.764102

Cited by 84 publications

(102 citation statements)

References 48 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significantly, degradation of Rad21 has been shown to be important for mating type silencing in S. cerevisiae (38). Recently, sumoylation of Swi6, Clr4, and Chp1 has been shown to be critical for stable silencing (50).…”

Section: Discussionmentioning

confidence: 99%

“…It would be interesting to identify the target/mediator of APC in silencing. Indeed, degradation of Cohesin has been shown to be important for silencing in S. cerevisiae (38). To check whether the lack of degradation of a putative target like Cdc13, Cut2, Rad21, or any other hitherto unknown target, resulting from an inefficient ubiquitylation, might be responsible for the silencing defect, we studied the effect of overexpression of ubiquitin gene in sng2-1, cut4-533, and cut9-665 mutants that exhibit silencing defect in the strain background mat1Msmto REII⌬ mat2::ura4, as shown in Fig.…”

Section: Defects In Centromeric Cohesin Recruitment and Chromosome Dymentioning

confidence: 99%

See 1 more Smart Citation

Interaction of APC/C-E3 Ligase with Swi6/HP1 and Clr4/Suv39 in Heterochromatin Assembly in Fission Yeast

Dubey¹,

Nakwal²,

Bisht³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Heterochromatin assembly in fission yeast is initiated by binding of Swi6/HP1 to the Lys-9-dimethylated H3 followed by spreading via cooperative recruitment of Swi6/HP1. Recruitment of Cohesin by Swi6/HP1 further stabilizes the heterochromatin structure and integrity. Subsequently, polyubiquitylation of Cut2 by anaphase-promoting complexcyclosome (APC/C)-ubiquitin-protein isopeptide ligase (E3 ligase) followed by degradation of Cut2 releases Cut1, which cleaves the Rad21 subunit of Cohesin, facilitating sister chromatid separation during mitosis. Here, we demonstrate a surprising role of APC/C in assembly of heterochromatin and silencing at mating type, centromere, and ribosomal DNA loci. Coincidentally with the loss of silencing, recruitment of Swi6, H3-Lys-9-Me2, and Clr4 at dg-dh repeats at cen1 and the K region of mat locus is abrogated in mutants cut4, cut9, and nuc2. Surprisingly, both Cut4 and Cut9 are also highly enriched at these regions in wild type and depleted in swi6⌬ mutant. Cut4 and Cut9 interact directly with Swi6/HP1 and Clr4, whereas the mutant Cut4 does not, suggesting that a direct physical interaction of APC subunits Cut4 and Cut9 with Swi6 and Clr4 is instrumental in heterochromatin assembly. The silencing defect in APC mutants is causally related to ubiquitylation activity of APC-E3 ligase. Like swi6 mutant, APC mutants are also defective in Cohesin recruitment and exhibit defects like lagging chromosomes, chromosome loss, and aberrant recombination in the mat region. In addition, APC mutants exhibit a bidirectional expression of dh repeats, suggesting a role in the RNA interference pathway. Thus, APC and heterochromatin proteins Swi6 and Clr4 play a mutually cooperative role in heterochromatin assembly, thereby ensuring chromosomal integrity, inheritance, and segregation during mitosis and meiosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Defects In Centromeric Cohesin Recruitment and Chromosome Dymentioning

confidence: 99%

Interaction of APC/C-E3 Ligase with Swi6/HP1 and Clr4/Suv39 in Heterochromatin Assembly in Fission Yeast

Dubey¹,

Nakwal²,

Bisht³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Loss of cohesion is essential to establish silencing at HMR, while loss of the Mcd1/Scc1 cohesin subunit allows silencing to be established prematurely (Lau et al 2002). In contrast, it was also observed that DNA replication factors needed to establish cohesion are also required for silencing at telomeres and the mating-type loci (Suter et al 2004).…”

Section: Cohesin and Yeast Gene Silencingmentioning

confidence: 99%

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

2006

View full text Add to dashboard Cite

The sister chromatid cohesion apparatus mediates physical pairing of duplicated chromosomes. This pairing is essential for appropriate distribution of chromosomes into the daughter cells upon cell division. Recent evidence shows that the cohesion apparatus, which is a significant structural component of chromosomes during interphase, also affects gene expression and development. The Cornelia de Lange (CdLS) and Roberts/SC phocomelia (RBS/SC) genetic syndromes in humans are caused by mutations affecting components of the cohesion apparatus. Studies in Drosophila suggest that effects on gene expression are most likely responsible for developmental alterations in CdLS. Effects on chromatid cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits.

show abstract

“…Interestingly, DNA replication and nuclear localization are not required for silencing establishment (17)(18)(19). Cell-cycle progression through M-phase, however, is required for silencing establishment, but progression through S-phase is required only at HMR and not at HML (5,20,21). Further, chromatin modifications influence the speed of the silencing establishment process.…”

mentioning

confidence: 99%

Symmetry, asymmetry, and kinetics of silencing establishment in Saccharomyces cerevisiae revealed by single-cell optical assays

Osborne

Hiraoka²,

Rine³

2011

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

View full text Add to dashboard Cite

In Saccharomyces cerevisiae, silent chromatin inhibits the expression of genes at the HML, HMR, and telomeric loci. When silent chromatin forms de novo, the rate of its establishment is influenced by different chromatin states. In particular, loss of the enzyme Dot1, an H3 K79 methyltransferase, leads to rapid silencing establishment. We tested whether silencing establishment was antagonized by H3 K79 methylation or by the Dot1 protein itself competing with Sir3 for binding sites on nucleosomes. To do so, we monitored fluorescence activity in cells containing a GFP gene within the HML locus during silencing establishment in a series of dot1 and histone mutant backgrounds. Silencing establishment rate was correlated with Dot1's enzymatic function rather than with the Dot1 protein itself. In addition, histone mutants that mimicked the conformation of unmethylated H3 K79 increased the rate of silencing establishment, indicating that the H3 K79 residue affected silencing independently of Dot1 abundance. Using fluorophore-based reporters, we confirmed that mother and daughter cells often silence in concert, but in instances where asymmetric silencing occurs, daughter cells established silencing earlier than their mothers. This noninvasive technique enabled us to demonstrate an asymmetry in silencing establishment of a key regulatory locus controlling cell fate.

show abstract

Cell-cycle control of the establishment of mating-type silencing in S. cerevisiae

Cited by 84 publications

References 48 publications

Interaction of APC/C-E3 Ligase with Swi6/HP1 and Clr4/Suv39 in Heterochromatin Assembly in Fission Yeast

Interaction of APC/C-E3 Ligase with Swi6/HP1 and Clr4/Suv39 in Heterochromatin Assembly in Fission Yeast

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

Symmetry, asymmetry, and kinetics of silencing establishment in Saccharomyces cerevisiae revealed by single-cell optical assays

Contact Info

Product

Resources

About