The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast

Ivanova, Alla V.; Bonaduce, Michael J.; Ivanov, Sergey V.; Klar, Amar J. S.

doi:10.1038/566

Cited by 162 publications

(126 citation statements)

References 27 publications

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“…Previous studies have demonstrated that chromo domain-containing proteins, including Su(var)3-9 and its orthologs, localize to regions of chromatin that are transcriptionally silenced (1,22,39). Our own subnuclear localization of SUV39H1 to electron-dense nuclear foci supports the notion that SUV39H1 may associate with transcriptionally inactive chromatin.…”

Section: Sbf1 Physically Associates With the Set Domain Of Suv39h1supporting

confidence: 86%

“…The functions of such domains have been implicated in the epigenetic control of developmental gene expression in Drosophila (38), proper sister chromatid segregation during meiosis (11), and telomeric and centromeric silencing in yeast (22,35). The molecular mechanisms that regulate these and other properties of higher-order chromatin are essentially unknown.…”

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confidence: 99%

“…These and other SET domain proteins have been shown to either physically or indirectly associate with chromatin (1,7,40). In yeast, mutations in the SET domains of CLR4 and SET1 disrupt centromeric silencing in Schizosaccharomyces pombe and telomeric silencing in Saccharomyces cerevisiae, respectively (22,35). Although found in over 30 proteins from human, Drosophila, Caenorhabditis elegans and yeast, the molecular functions for SET domains are not known.…”

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confidence: 99%

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Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

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Mammalian SET domain-containing proteins define a distinctive class of chromatin-associated factors that are targets for growth control signals and oncogenic activation. SUV39H1, a mammalian ortholog of Drosophila Su(var)3-9, contains both SET and chromo domains, signature motifs for proteins that contribute to epigenetic control of gene expression through effects on the regional organization of chromatin structure. In this report we demonstrate that SUV39H1 represses transcription in a transient transcriptional assay when tethered to DNA through the GAL4 DNA binding domain. Under these conditions, SUV39H1 displays features of a long-range repressor capable of acting over several kilobases to silence basal promoters. A possible role in chromatin-mediated gene silencing is supported by the localization of exogenously expressed SUV39H1 to nuclear bodies with morphologic features suggestive of heterochromatin in interphase cells. In addition, we show that SUV39H1 is phosphorylated specifically at the G 1 /S cell cycle transition and when forcibly expressed suppresses cell growth. Growth suppression as well as the ability of SUV39H1 to form nuclear bodies and silence transcription are antagonized by the oncogenic antiphosphatase Sbf1 that when hyperexpressed interacts with the SET domain and stabilizes the phosphorylated form of SUV39H1. These studies suggest a phosphorylation-dependent mechanism for regulating the chromatin organizing activity of a mammalian su(var) protein and implicate the SET domain as a gatekeeper motif that integrates upstream signaling pathways to epigenetic regulation and growth control.The formation and propagation of higher-order chromatin states are dynamic processes that establish distinct domains that are either permissive or restrictive for transcription. The functions of such domains have been implicated in the epigenetic control of developmental gene expression in Drosophila (38), proper sister chromatid segregation during meiosis (11), and telomeric and centromeric silencing in yeast (22,35). The molecular mechanisms that regulate these and other properties of higher-order chromatin are essentially unknown.Genetic analyses in Drosophila and yeast have identified several genes that participate in the formation of euchromatin or heterochromatin states. Some of these encode proteins that contribute to either an enhancement [E(var)] or suppression [Su(var)] of position effect variegation (PEV) (42). PEV is a gene silencing mechanism that results from the spreading of heterochromatin, thus implicating E(var) and Su(var) proteins in the formation of euchromatic and heterochromatic domains, respectively. Several E(var) and Su(var) proteins share distinctive motifs that are important for their ability to organize chromatin domains. The Su(var)3-9 protein and its mammalian ortholog SUV39H1 are unique in being the only characterized PEV modifiers that share two of these consensus motifs, the chromo and SET domains (1, 50). Chromo domains are 40-amino-acid modular motifs that are implicated in...

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Section: Sbf1 Physically Associates With the Set Domain Of Suv39h1supporting

confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

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“…Concerning Suv(ar)3-9, inactivation of its homologue Clr4 by mutation in the yeast Schizosaccharomyces pombe relieves heterochromatin silencing at centromeres (Ivanova et al, 1998). Since HP1 is known to interact with Suv(ar)3-9 (Aagaard et al, 1999), it is reasonable to suppose that HP1 might be involved in the silencing function of Suv(ar)3-9.…”

Section: Spatio-temporal Chromatin Organization and Regulation Of Genmentioning

confidence: 99%

The Rb/chromatin connection and epigenetic control: opinion

Ferreira¹,

Naguibneva²,

Pritchard³

et al. 2001

Oncogene

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The balance between cell di erentiation and proliferation is regulated at the transcriptional level. In the cell cycle, the transition from G1 to S phase (G1/S transition) is of paramount importance in this regard. Indeed, it is only before this point that cells can be oriented toward the di erentiation pathway: beyond, cells progress into the cycle in an autonomous manner. The G1/S transition is orchestrated by the transcription factor E2F. E2F controls the expression of a group of checkpoint genes whose products are required either for the G1-to-S transition itself or for DNA replication (e.g. DNA polymerase a). E2F activity is repressed in growth-arrested cells and in early G1, and is activated at mid-to-late G1. E2F is controlled by the retinoblastoma tumor suppressor protein Rb. Rb represses E2F mainly by recruiting chromatin remodeling factors (histone deacetylases and SWI/SNF complexes), the DNA methyltransferase DNMT1, and a histone methyltransferase. This review will focus on the molecular mechanisms of E2F repression by Rb during the cell cycle and during cell-cycle exit by di erentiating cells. A model in which Rb irreversibly represses E2F-regulated genes in di erentiated cells by an epigenetic mechanism linked to heterochromatin, and involving histone H3 and promoter DNA methylation, is discussed. Oncogene (2001) 20, 3128 ± 3133.

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“…Heterochromatin proteins, in particular Swi6/HP1, aid in donor choice (5,9). Factors that affect Swi6 localization at the mat locus impair mating-type switching (17)(18)(19)(20)(21). Swi6 facilitates cell-type-specific spreading of a recombination-promoting complex (RPC) (18).…”

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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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The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast

Cited by 162 publications

References 27 publications

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

The Rb/chromatin connection and epigenetic control: opinion

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

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