The proper connection between shelterin components is required for telomeric heterochromatin assembly

Wang, Jiyong; Cohen, Allison; Letian, Anudari; Tadeo, Xavier; Moresco, James J.; Liu, Jinqiang; Yates, John R.; Qiao, Feng; Jia, Songtao

doi:10.1101/gad.266718.115

Cited by 50 publications

(76 citation statements)

References 66 publications

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“…The Shelterin complex recruits CLRC and SHREC to the telomeres, from where they spread to maintain subtelomeric heterochromatin (Kanoh et al 2005;Sugiyama et al 2007;Wang et al 2016). In caf1Δdcr1Δ cells, Taz1, a DNA binding protein of the Shelterin complex, is still recruited to the telomeric repeats (Supplemental Fig.…”

Section: Heterochromatin Is Lost At Transcribed Regionsmentioning

confidence: 99%

“…At those loci, heterochromatin maintenance is RNAi independent, but RNAi is required to establish heterochromatin (Kanoh et al 2005;Hansen et al 2006;Allshire and Ekwall 2015). At subtelomeres, the Shelterin complex binds telomeres and recruits the CLRC methyltransferase and the SHREC deacetylase complexes to maintain heterochromatin (Kanoh et al 2005;Hansen et al 2006;Sugiyama et al 2007;Motamedi et al 2008;Tadeo et al 2013;Wang et al 2016). At the mat locus, the cenH element shares homology with the centromeric repeats and is essential for RNAi-mediated heterochromatin establishment .…”

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confidence: 99%

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Accumulation of RNA on chromatin disrupts heterochromatic silencing

Brönner¹,

Salvi²,

Zocco³

et al. 2017

Genome Res.

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Long noncoding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics, and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe that heterochromatin is lost at transcribed regions in the absence of RNA degradation. We show that heterochromatic RNAs are retained on chromatin, form DNA: RNA hybrids, and need to be degraded by the Ccr4-Not complex or RNAi to maintain heterochromatic silencing. The Ccr4-Not complex is localized to chromatin independently of H3K9me and degrades chromatin-associated transcripts, which is required for transcriptional silencing. Overexpression of heterochromatic RNA, but not euchromatic RNA, leads to chromatin localization and loss of silencing of a distant ade6 reporter in wild-type cells. Our results demonstrate that chromatin-bound RNAs disrupt heterochromatin organization and need to be degraded in a process of heterochromatin formation.

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Section: Heterochromatin Is Lost At Transcribed Regionsmentioning

confidence: 99%

mentioning

confidence: 99%

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Brönner¹,

Salvi²,

Zocco³

et al. 2017

Genome Res.

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Section: Editorialmentioning

confidence: 99%

“…The shelterin complex can recruit the histone H3K9 methyltransferase The Epigenetic Trends in Telomere Research complex CLRC to establish subtelomeric heterochromatin. And the proper connection of shelterin components, which allows CLRC to skip telomeric repeats to internal regions, is also required for the subtelomeric heterochromatin assembly [5].Another characteristic of telomeric chromatin is lower acetylation of histones H3 and H4 at both telomeric and subtelomeric regions [6]. In addition, unlike the telomere TTAGGG sequence, subtelomeric DNA contains CpG dinucleotides heavily methylated by DNA methyltransferases DNMT1, DNMT3a and DNMT3b.…”

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confidence: 99%

The Epigenetic Trends in Telomere Research

Wang¹

2017

J Clin Epigenet

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EditorialThe aging of organisms starts from a single cell at the molecular level. It includes changes related to telomere shortening, cell senescence and epigenetic modifications variation. These processes can accumulate over the lifespan. Research studies show that epigenetic signaling contributes to aging, human disease, and tumorigenesis. Epigenetic DNA modifications involve changes in the gene activity but not in the DNA sequence. An epigenome consists of modifications to the DNA and histone proteins without the changes in the DNA sequence itself. On the other hand, mounting evidence describes the great impact of telomeres on dynamics of aging, longevity, human health, and the development of many genetic diseases [1].Telomeres are the protective heterochromatic nucleoprotein structures capping the physical ends of linear eukaryotic chromosomes and play a key role in preserving genomic stability. They consist of telomeric repeat DNA, lots of specialized proteins, and RNA. Telomeric DNA is composed of dsRNA repeats followed by a single-stranded overhang and has been suggested to form nonnucleosomal structures. The basic function of telomeres is to separate natural chromosome ends from unrepaired doublestranded DNA breaks and to protect the coding parts of the genome from the loss due to the incomplete replication of the distal region of the lagging DNA strand.Telomere chromatin and the adjacent subtelomeric regions in mammals are organized in nucleosomes similar to the rest of chromosomal DNA, but with a shorter nucleosomal spacing. Telomeric chromatin shares some characteristics with pericentromeric heterochromatin in terms of sequence organization and epigenetic marks. Human telomeres are exclusively repetitive sequences whereas subtelomeres contain less organized degenerative repeats and various other sequences and include a low density of genes [2]. Depending on their length, telomeres have the ability to silence the transcription of nearby genes, through a variegation based phenomenon known as 'telomere position effect' (TPE) [3,4]. Mammalian telomeres and subtelomeres carry features of heterochromatin in that they contain HP1 proteins and heterochromatin-typical histone marks including H4K20me3 and H3K9me3. The repeat elements at subtelomere can initiate heterochromatin through an RNAimediated pathway. In addition, the telomere-binding protein complex shelterin also initiates heterochromatin at telomeres. The shelterin complex can recruit the histone H3K9 methyltransferase The Epigenetic Trends in Telomere Research complex CLRC to establish subtelomeric heterochromatin. And the proper connection of shelterin components, which allows CLRC to skip telomeric repeats to internal regions, is also required for the subtelomeric heterochromatin assembly [5].Another characteristic of telomeric chromatin is lower acetylation of histones H3 and H4 at both telomeric and subtelomeric regions [6]. In addition, unlike the telomere TTAGGG sequence, subtelomeric DNA contains CpG dinucleotides heavily methylated by DNA me...

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“…One is the telomere-binding protein complex called shelterin; the other is the RNAi machinery, which acts at the centromere-homologous (cenH) sequence (the template of siRNA) within the tlh1/2 + genes in the subtelomeres. After a methyltransferase, Clr4, methylates H3K9 and an HP1 homolog, Swi6, is recruited to the telomere-proximal sites, the heterochromatin spreads out around the subtelomeric homologous regions, presumably via the association of Swi6 with itself and Clr4 (Hall et al, 2002;Cam et al, 2005;Kanoh et al, 2005;Wang et al, 2016) (Fig. 3A).…”

Section: Introductionmentioning

confidence: 99%

Unexpected roles of a shugoshin protein at subtelomeres

Kanoh

2017

Genes Genet. Syst.

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A chromosome is composed of structurally and functionally distinct domains. Telomeres, which are located at the ends of linear chromosomes, play crucial roles in genome stability. Although substantial knowledge of telomeres has been accumulated, the regulation and function of subtelomeres, which are the domains adjacent to telomeres, remain largely unknown. In this review, I describe recent discoveries about the multiple roles of a shugoshin family protein, Sgo2, which is localized at centromeres in mitosis and contributes to precise chromosome segregation, in defining chromatin structure and functions of the subtelomeres in fission yeast. Sgo2 becomes enriched at the subtelomeres, particularly during G 2 phase, and is essential for the formation of a highly condensed subtelomeric chromatin body called the knob. Furthermore, Sgo2 maintains the expression levels of subtelomeric genes and the timing of DNA replication at subtelomeric late origins.

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The proper connection between shelterin components is required for telomeric heterochromatin assembly

Cited by 50 publications

References 66 publications

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Accumulation of RNA on chromatin disrupts heterochromatic silencing

The Epigenetic Trends in Telomere Research

Unexpected roles of a shugoshin protein at subtelomeres

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