Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance

Buscaino, Alessia; Lejeune, Erwan; Audergon, Pauline N. C. B.; Hamilton, Georgina L.; Pidoux, Alison L.; Allshire, Robin C.

doi:10.1038/emboj.2013.72

Cited by 71 publications

(119 citation statements)

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“…3C; Sadaie et al 2004). The histone deacetylases Clr3 and Sir2 function cooperatively with RNAi to establish heterochromatin at pericentric repeats, and H3K9me2 is completely abolished in clr3D dcr1D and sir2D dcr1D cells (Yamada et al 2005;Alper et al 2013;Buscaino et al 2013;Marina et al 2013). The results that poz1D dcr1D cells maintained preexisting heterochromatin but failed to establish heterochromatin de novo suggest that the residual H3K9me in dcr1D cells is necessary for poz1D dcr1D cells to maintain pericentric heterochromatin.…”

Section: Bypassing Rnai Requires Rnai-independent Heterochromatin Assmentioning

confidence: 67%

“…However, even at pericentric regions, H3K9me and Swi6 are still present in RNAi mutants, albeit at lower levels, suggesting the existence of RNAi-independent mechanisms to establish heterochromatin (Sadaie et al 2004). These pathways involve the Clr3 and Sir2 histone deacetylases since H3K9me levels are further reduced from pericentric regions in clr3D dcr1D and sir2D dcr1D cells, although Sir2 seems to function in a separate pathway from Clr3 (Yamada et al 2005;Alper et al 2013;Buscaino et al 2013;Marina et al 2013).…”

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confidence: 99%

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Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

et al. 2013

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The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causes pericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterin components restores pericentric heterochromatin and its functions in RNAi mutants. We further isolated a separation-of-function mutant of Poz1 and revealed that defective telomere silencing, but not telomere length control, is critical for bypassing RNAi. Further analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi mutants releases heterochromatin protein Swi6, which is redistributed to pericentric regions through RNAiindependent heterochromatin assembly pathways. Given the high mobility of Swi6 protein and that increased levels of Swi6 facilitates heterochromatin spreading as well as ectopic heterochromatin assembly, our results suggest that constitutive heterochromatin domains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatin formation.

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Section: Bypassing Rnai Requires Rnai-independent Heterochromatin Assmentioning

confidence: 67%

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confidence: 99%

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

et al. 2013

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“…In addition, the chromodomain protein HP1 binds methylated H3K9. This type of heterochromatin is best characterized in Schizosaccharomyces pombe, where heterochromatin is established in part through siRNA-presenting Argonaute proteins (19) and is maintained by histone deacetylases, such as Sir2 and Clr3 (20,21).…”

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Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin

Kapoor

Zhu

Froyd

et al. 2015

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

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Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeast Candida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4-4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin in C. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and a URA3 reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin.centromere | heterochromatin | Candida | CSE4 | Sir2

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“…The interaction between small RNAs and chromatin remodeling factors is reciprocal. For example, heterochromatin is highly enriched for histone H3 lysine 9 trimethylation (H3K9me3), which is known to be involved in transcriptional gene silencing [80]. In Schizosaccharomyces pombe, not only can RNAi direct deposition of H3K9me3 marks on specific gene targets, the deposited histone mark can also facilitate new rounds of RNAi machinery recruitment, thus engaging a sustainable and self-reinforcing feedforward loop [81,82].…”

Section: Mechanisms That Enable Long-lasting Rnaimentioning

confidence: 99%

Guest list or black list: heritable small RNAs as immunogenic memories

Rechavi

2014

Trends in Cell Biology

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Small RNA-mediated gene silencing plays a pivotal role in genome immunity by recognizing and eliminating viruses and transposons which otherwise may colonize the genome. However, this can be challenging since individual genomic parasites are highly diverse, and employ multiple immune evasion techniques. In this review, I discuss a new theory proposing that the integrity of the germline is maintained by transgenerationally-transmitted RNA "memories" that record ancestral gene expression patterns, and delineate "Self" from "Foreign" sequences. To maintain such recollection two tactics are employed in parallel: "black listing" of invading nucleic acids, and "guest listing" of endogenous genes. Studies in a number of organisms have shown that this memorization is used by the next generation small RNAs to act as "Inherited Vaccines" that ambush invading elements, or as "Inherited Licenses" that grant the transcription of autogenous sequences. KeywordsSmall RNA; Transgenerational Inheritance; Inherited Immunity; Self Vs. Non-Self; "Inherited Vaccines" Overview of transgenerational inheritanceEvolution progresses through an interplay between two major forces, selection and variation. Since the formulation of the Modern Synthesis the theory holds that the environment is limited in its contribution to the evolutionary course of action -it affects selection, but not the degree of variation [1,2]. However, recent discoveries in epigenetics suggest that the environment may influence variability as well [1]. If the parental environment is predictive of the conditions that the progeny will face (often for sessile or short-lived organisms), epigenetic responses can change the output of the encoded genetic information in an adaptive manner [3]. For example, the water flea Daphnia changes its normal developmental course and develops a "helmet" that protects it from predators, if it is born to a mother that survived a similar attack [4].Correspondence to: odedrechavi@gmail.com. Over the years, controversy surrounded the study of environmentally affected transgenerational inheritance. Today, an improved understanding of epigenetic mechanisms at the molecular level has provided a logical background to explain how, heretically, an adaptive acquired trait could become heritable [5]. Several epigenetic mechanisms could regulate the expression of relevant genes during transgenerational inheritance including DNA methylation, histone modification, and transmission of regulatory RNAs. Moreover, in many organisms, these pathways appear to be interconnected [5][6][7][8]. Europe PMC Funders GroupThis review will concentrate on recent discoveries that establish a role for small RNAs in transgenerational transmission of acquired defense. Furthermore, exciting examples of RNA-mediated non-Mendelian genetic effects will be discussed, along with their possible implications for the study of evolution and immunology. RNA-mediated gene silencing and inheritanceSince the original discovery that small RNAs derived from exogenously-provided dou...

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Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance

Cited by 71 publications

References 69 publications

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin

Guest list or black list: heritable small RNAs as immunogenic memories

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