SIR Proteins and the Assembly of Silent Chromatin in Budding Yeast

Kueng, Stephanie; Oppikofer, Mariano; Gasser, Susan M.

doi:10.1146/annurev-genet-021313-173730

Cited by 119 publications

(122 citation statements)

References 256 publications

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“…Similarly, RNAi knockdown of the transcription facilitating histone chaperone suppressor of ty 16 (TbSPT16) or the SWI2/SNF2-related chromatin-remodeling protein TbISWI or deletion of histone deacetylase sirtuin 2-related protein 1 (TbSIR2RP1) each increases transcription near the promoter but not the VSG gene of silent ESs (12)(13)(14). These results indicate that the control of ES transcription involves telomeric silencing (15), which entails the functions and interactions of multiple proteins and chromatin remodeling (16,17), but importantly, what regulates these processes is unknown.…”

mentioning

confidence: 97%

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Cestari

Stuart

2015

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

143

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African trypanosomes evade clearance by host antibodies by periodically changing their variant surface glycoprotein (VSG) coat. They transcribe only one VSG gene at a time from 1 of about 20 telomeric expression sites (ESs). They undergo antigenic variation by switching transcription between telomeric ESs or by recombination of the VSG gene expressed. We show that the inositol phosphate (IP) pathway controls transcription of telomeric ESs and VSG antigenic switching in Trypanosoma brucei. Conditional knockdown of phosphatidylinositol 5-kinase (TbPIP5K) or phosphatidylinositol 5-phosphatase (TbPIP5-Pase) or overexpression of phospholipase C (TbPLC) derepresses numerous silent ESs in T. brucei bloodstream forms. The derepression is specific to telomeric ESs, and it coincides with an increase in the number of colocalizing telomeric and RNA polymerase I foci in the nucleus. Monoallelic VSG transcription resumes after reexpression of TbPIP5K; however, most of the resultant cells switched the VSG gene expressed. TbPIP5K, TbPLC, their substrates, and products localize to the plasma membrane, whereas TbPIP5Pase localizes to the nucleus proximal to telomeres. TbPIP5Pase associates with repressor/activator protein 1 (TbRAP1), and their telomeric silencing function is altered by TbPIP5K knockdown. These results show that specific steps in the IP pathway control ES transcription and antigenic switching in T. brucei by epigenetic regulation of telomere silencing.O nly one of the ∼20 telomeric expression sites (ESs) is transcribed at a time in Trypanosoma brucei in the mammalian infectious stage bloodstream (BF) or metacyclic forms (MFs), whereas no ES is transcribed in the insect stage procyclic forms (PFs) (1). Each ES contains 1 telomeric variant surface glycoprotein (VSG) gene, whose expression confers a distinct cellular antigenic type and up to 12 expression site-associated genes (ESAGs) whose functions are incompletely understood ( Fig. 1A) (2-4). The parasites evade immune clearance by periodically changing antigenic type by switching transcription between ESs or by ES recombination with the ∼2,500 non-ES VSG genes and pseudogenes (5, 6). ESs are transcribed by RNA polymerase I (Pol I), which initiates at the single promoter at all ESs but terminates within a few kilobases except at one fully transcribed ES (7,8).RNAi knockdown of expression of the nuclear protein TbRAP1 that interacts with the TTAGGG-binding factor (TbTRF) or of the nuclear lamina protein 1 (TbNUP1) or deletion of the histonelysine N-methyltransferase DOT1B (TbDOT1B) alleles each results in transcription of silent ESs (9-11). Similarly, RNAi knockdown of the transcription facilitating histone chaperone suppressor of ty 16 (TbSPT16) or the SWI2/SNF2-related chromatin-remodeling protein TbISWI or deletion of histone deacetylase sirtuin 2-related protein 1 (TbSIR2RP1) each increases transcription near the promoter but not the VSG gene of silent . These results indicate that the control of ES transcription involves telomeric silencing (15), which entails...

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mentioning

confidence: 97%

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Cestari

Stuart

2015

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

143

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“…The silent HML and HMR loci are flanked by the sequences to which Silent Information Regulator (SIR) proteins are recruited (Figure 1a) [26]. These histone-modifying proteins do not recognize specific DNA sequences by themselves.…”

Section: Heterochromatin Formation and Transcription Regulationmentioning

confidence: 99%

“…These histone-modifying proteins do not recognize specific DNA sequences by themselves. Therefore, the recruitment of the SIR proteins to the boundaries of the silent loci requires additional DNA-binding proteins, such as Abf1, Rap1, and ORC [26]. ORC1 plays a key role in this process (Figure 1a).…”

Section: Heterochromatin Formation and Transcription Regulationmentioning

confidence: 99%

Nonreplicative functions of the origin recognition complex

Popova

Brechalov

Георгиева

et al. 2018

Nucleus

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Origin recognition complex (ORC), a heteromeric six-subunit complex, is the central component of the eukaryotic pre-replication complex. Recent data from yeast, frogs, flies and mammals present compelling evidence that ORC and its individual subunits have nonreplicative functions as well. The majority of these functions, such as heterochromatin formation, chromosome condensation, and segregation are dependent on ORC-DNA interactions. Furthermore, ORC is involved in the control of cell division via its participation in centrosome duplication and cytokinesis. Recent findings have also demonstrated a direct interaction between ORC and mRNPs and highlighted an essential role of ORC in mRNA nuclear export. Along with the growth of evolutionary complexity of organisms, ORC complex functions become more elaborate and new functions of the ORC sub-complexes and individual subunits have emerged.

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“…In the budding yeast Saccharomyces cerevisiae, the 32 telomeres of haploid cells cluster into three to eight foci, which are usually enriched at the nuclear periphery under wild-type conditions (Kueng et al, 2013;Wellinger and Zakian, 2012). The telomere anchoring to the periphery is mediated by two redundant pathways; interactions between Sir4, a telomere-associated protein, and Esc1 and Mps3, inner nuclear membrane proteins, or between Yku80 and telomerase and Mps3 (Taddei et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Sphingolipids regulate telomere clustering by affecting transcriptional levels of genes involved in telomere homeostasis

Ikeda

Muneoka

Murakami

et al. 2015

Journal of Cell Science

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In eukaryotic organisms, including mammals, nematodes and yeasts, the ends of chromosomes, telomeres are clustered at the nuclear periphery. Telomere clustering is assumed to be functionally important because proper organization of chromosomes is necessary for proper genome function and stability. However, the mechanisms and physiological roles of telomere clustering remain poorly understood. In this study, we demonstrate a role for sphingolipids in telomere clustering in the budding yeast Saccharomyces cerevisiae. Because abnormal sphingolipid metabolism causes downregulation of expression levels of genes involved in telomere organization, sphingolipids appear to control telomere clustering at the transcriptional level. In addition, the data presented here provide evidence that telomere clustering is required to protect chromosome ends from DNA-damage checkpoint signaling. As sphingolipids are found in all eukaryotes, we speculate that sphingolipid-based regulation of telomere clustering and the protective role of telomere clusters in maintaining genome stability might be conserved in eukaryotes.

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SIR Proteins and the Assembly of Silent Chromatin in Budding Yeast

Cited by 119 publications

References 256 publications

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes

Nonreplicative functions of the origin recognition complex

Sphingolipids regulate telomere clustering by affecting transcriptional levels of genes involved in telomere homeostasis

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