Inner nuclear membrane protein Ima1 is dispensable for intranuclear positioning of centromeres

Hiraoka, Yasushi; Maekawa, Hiromi; Asakawa, Haruhiko; Chikashige, Yuji; Kojidani, Tomoko; Osakada, Hiroko; Matsuda, Atsushi; Haraguchi, Tokuko

doi:10.1111/j.1365-2443.2011.01544.x

Cited by 64 publications

(92 citation statements)

References 65 publications

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“…5B). Cut11 is a nuclear membrane protein whose ortholog, Ndc1, is a component of the nuclear pore complex (West et al 1998;Brohawn et al 2009), while Lem2 is an inner nuclear membrane protein (Hiraoka et al 2011). We found that Dsh1-13myc localized at the nuclear periphery but rarely colocalized with the Cut11 foci and tended to localize more proximal to nucleoplasm than Cut11 (Fig.…”

Section: Binding Of Rdrc To Heterochromatin Requires Dsh1mentioning

confidence: 69%

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A novel RNAi protein, Dsh1, assembles RNAi machinery on chromatin to amplify heterochromatic siRNA

et al. 2012

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In fission yeast, siRNA is generated from pericentromeric noncoding RNA by the RNAi machinery. siRNA synthesis and heterochromatin formation are interdependent, forming a self-reinforcing loop on chromatin. In this system, siRNA is amplified by the RNA-dependent RNA polymerase complex (RDRC) and the endoribonuclease Dcr1, which synthesizes dsRNA and processes the dsRNA, respectively. The amplification is essential for stable heterochromatin formation. Here, a novel gene, dsh1 + (defect of the gene silencing at centromeric heterochromatin), is identified as an essential component of RNAi-directed heterochromatin assembly. Loss of dsh1 + abolishes normal RNAi function and heterochromatic gene silencing at pericentromeres. Dsh1 interacts with Dcr1 and RDRC and couples the reactions of both proteins to the effective production of siRNA in vivo. Dsh1 binds to heterochromatin in the absence of RDRC, while RDRC requires Dsh1 for its chromatin-binding activity, suggesting that Dsh1 recruits RDRC to chromatin. Immunofluorescence analysis shows that Dsh1 forms foci at the nuclear periphery, and some Dsh1 foci colocalize with Dcr1 and RDRC. Dsh1 is required for the colocalization of Dcr1 and RDRC. Moreover, loss of the nuclear periphery localization of Dsh1 abolishes Dsh1 function. Taken together, these results suggest that Dsh1 assembles the RNAi machinery on heterochromatin and forms a perinuclear compartment for amplification of heterochromatic siRNA.

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Section: Binding Of Rdrc To Heterochromatin Requires Dsh1mentioning

confidence: 69%

“…Since we observed one of the Dsh1 foci colocalized or closely localized with Cnp1 (Fig. 2D,E), and Lem2 was shown to localize to the spindle pole body (Hiraoka et al 2011), the colocalization of Dsh1 and Lem2 appeared to occur at the spindle pole body, where centromeric heterochromatin clustered.…”

Section: Binding Of Rdrc To Heterochromatin Requires Dsh1mentioning

confidence: 99%

A novel RNAi protein, Dsh1, assembles RNAi machinery on chromatin to amplify heterochromatic siRNA

et al. 2012

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“…This verifies IF data that show that Ima1 specifically binds to heterochromatic regions. However, Ima1 is dispensable for the tethering of centromeric DNA to the SPB region of the nuclear periphery (King et al 2008;Hiraoka et al 2011). Rather, the Ima1-interacting loci are enriched with the RNAi components, Dcr1 and Rdp1.…”

Section: Nuclear Organization In S Pombementioning

confidence: 99%

Epigenetic Regulation of Chromatin States inSchizosaccharomyces pombe

Allshire

Ekwall

2015

Cold Spring Harb Perspect Biol

177

191

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SUMMARYThis article discusses the advances made in epigenetic research using the model organism fission yeast Schizosaccharomyces pombe. S. pombe has been used for epigenetic research since the discovery of position effect variegation (PEV). This is a phenomenon in which a transgene inserted within heterochromatin is variably expressed, but can be stably inherited in subsequent cell generations. PEV occurs at centromeres, telomeres, ribosomal DNA (rDNA) loci, and mating-type regions of S. pombe chromosomes. Heterochromatin assembly in these regions requires enzymes that modify histones and the RNA interference (RNAi) machinery. One of the key histone-modifying enzymes is the lysine methyltransferase Clr4, which methylates histone H3 on lysine 9 (H3K9), a classic hallmark of heterochromatin. The kinetochore is assembled on specialized chromatin in which histone H3 is replaced by the variant CENP-A. Studies in fission yeast have contributed to our understanding of the establishment and maintenance of CENP-A chromatin and the epigenetic activation and inactivation of centromeres.Outline

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“…), which could explain the partial suppression of the silencing defect in these double mutants. In conclusion, whereas Lem2, Man1, and Ima1 may have overlapping roles in other pathways (Hiraoka et al 2011), heterochromatic silencing is exclusively mediated by Lem2.…”

Section: Ura4mentioning

confidence: 99%

“…Two INM proteins, Man1 and Ima1, have been reported to have overlapping functions with Lem2 in ensuring nuclear membrane integrity (Hiraoka et al 2011). In addition, Man1 was shown to associate with subtelomeric regions (Steglich et al 2012), which may suggest a role in telomeric silencing.…”

Section: Ura4mentioning

confidence: 99%

Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

et al. 2016

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Transcriptionally silent chromatin localizes to the nuclear periphery, which provides a special microenvironment for gene repression. A variety of nuclear membrane proteins interact with repressed chromatin, yet the functional role of these interactions remains poorly understood. Here, we show that, in Schizosaccharomyces pombe, the nuclear membrane protein Lem2 associates with chromatin and mediates silencing and heterochromatin localization. Unexpectedly, we found that these functions can be separated and assigned to different structural domains within Lem2, excluding a simple tethering mechanism. Chromatin association and tethering of centromeres to the periphery are mediated by the N-terminal LEM (LAP2-Emerin-MAN1) domain of Lem2, whereas telomere anchoring and heterochromatin silencing require exclusively its conserved C-terminal MSC (MAN1-Src1 C-terminal) domain. Particularly, silencing by Lem2 is epistatic with the Snf2/HDAC (histone deacetylase) repressor complex SHREC at telomeres, while its necessity can be bypassed by deleting Epe1, a JmjC protein with anti-silencing activity. Furthermore, we found that loss of Lem2 reduces heterochromatin association of SHREC, which is accompanied by increased binding of Epe1. This reveals a critical function of Lem2 in coordinating these antagonistic factors at heterochromatin. The distinct silencing and localization functions mediated by Lem2 suggest that these conserved LEM-containing proteins go beyond simple tethering to play active roles in perinuclear silencing.

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Inner nuclear membrane protein Ima1 is dispensable for intranuclear positioning of centromeres

Cited by 64 publications

References 65 publications

A novel RNAi protein, Dsh1, assembles RNAi machinery on chromatin to amplify heterochromatic siRNA

A novel RNAi protein, Dsh1, assembles RNAi machinery on chromatin to amplify heterochromatic siRNA

Epigenetic Regulation of Chromatin States inSchizosaccharomyces pombe

Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

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