RNAi and Heterochromatin Assembly

Martienssen, Robert A.; Moazed, Danesh

doi:10.1101/cshperspect.a019323

Cited by 270 publications

(285 citation statements)

References 123 publications

(155 reference statements)

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“…Silent chromatin domains of Saccharomyces cerevisiae are epigenetically inherited and exhibit variegated expression under certain circumstances. In contrast to heterochromatin in Schizosaccharomyces pombe and higher eukaryotes, budding yeast silent chromatin lacks a number of hallmark characteristics including methylation of histones, heterochromatin protein 1 (HP1), and the participation of RNA interference (RNAi) (Martienssen and Moazed 2015). In essence, S. cerevisiae silent chromatin is a stripped-down version of heterochromatin found in other organisms.…”

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confidence: 99%

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD + -dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the "nuts and bolts" of silent chromatin and the processes that yield transcriptional silencing.

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The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

2016

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“…To amplify small RNAs, RITS recruits the RNA-dependent RNA Polymerase complex (RDRC), which synthesizes doublestranded RNA that is processed by Dicer into siRNAs. In addition, RITS recruits the H3K9 methyltransferase complex CLRC to chromatin, which leads to repressive histone 3 lysine 9 methylation (H3K9me), recruitment of HP1 proteins, and heterochromatin formation (Volpe et al 2002;Verdel et al 2004;Allshire and Ekwall 2015;Holoch and Moazed 2015;Martienssen and Moazed 2015;Zocco et al 2016).…”

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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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“…However, as with repeat density, piRNA sequence density by itself is also an insufficient predictor of transgene phenotypes ( Figure 6; Table S4), indicating that multiple conditions have to be met for stable heterochromatin to form, possibly including low levels of transcription coming from the transgene locus at the correct developmental time, when heterochromatin is being established. A model that depends on some transcription to achieve silencing, apparently by generating a transcript, which can hybridize with the available piRNAs to initiate silencing events, is well established in the yeast Schizosaccharomyces pombe (Martienssen and Moazed 2015). Mapping the insertion sites of variegating reporters recovered in our screen revealed that for both the P{T1} and the P{T4} transgenes the majority of the insertion sites are in regions of the genome previously described as supporting heterochromatin formation and PEV.…”

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confidence: 97%

Targeting of P-Element Reporters to Heterochromatic Domains by Transposable Element 1360 in Drosophila melanogaster

et al. 2015

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Heterochromatin is a common DNA packaging form employed by eukaryotes to constitutively silence transposable elements. Determining which sequences to package as heterochromatin is vital for an organism. Here, we use Drosophila melanogaster to study heterochromatin formation, exploiting position-effect variegation, a process whereby a transgene is silenced stochastically if inserted in proximity to heterochromatin, leading to a variegating phenotype. Previous studies identified the transposable element 1360 as a target for heterochromatin formation. We use transgene reporters with either one or four copies of 1360 to determine if increasing local repeat density can alter the fraction of the genome supporting heterochromatin formation. We find that including 1360 in the reporter increases the frequency with which variegating phenotypes are observed. This increase is due to a greater recovery of insertions at the telomereassociated sequences (50% of variegating inserts). In contrast to variegating insertions elsewhere, the phenotype of telomere-associated sequence insertions is largely independent of the presence of 1360 in the reporter. We find that variegating and fully expressed transgenes are located in different types of chromatin and that variegating reporters in the telomere-associated sequences differ from those in pericentric heterochromatin. Indeed, chromatin marks at the transgene insertion site can be used to predict the eye phenotype. Our analysis reveals that increasing the local repeat density (via the transgene reporter) does not enlarge the fraction of the genome supporting heterochromatin formation. Rather, additional copies of 1360 appear to target the reporter to the telomere-associated sequences with greater efficiency, thus leading to an increased recovery of variegating insertions. KEYWORDS heterochromatin; transposable elements; position-effect variegation; chromatin; Drosophila I N vivo regulation of gene expression occurs in the context of chromatin, the complex structure formed by DNA, histones, and a variety of associated proteins. Two basic types of chromatin were originally distinguished, euchromatin and heterochromatin, based on cytological staining behavior during the cell cycle (Heitz 1928). Euchromatin and heterochromatin differ in a number of characteristics, including biochemical makeup and their effect on the expression of transgene reporters. Euchromatin is generally accessible for transcription, contains the majority of the genes, and is characterized by biochemical marks associated with transcription, such as high levels of histone acetylation, transcriptional activators, and RNA polymerase II. In contrast, heterochromatin contains few genes and has a high repeat density. Heterochromatin is characterized by low levels of histone acetylation, high levels of histone 3 lysine 9 (H3K9) methylation, and the presence of "silencing" proteins such as heterochromatin protein 1 (HP1) (Beisel and Paro 2011). While this model of two basic chromatin types has been very successful...

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RNAi and Heterochromatin Assembly

Cited by 270 publications

References 123 publications

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Targeting of P-Element Reporters to Heterochromatic Domains by Transposable Element 1360 in Drosophila melanogaster

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