Global regulation of heterochromatin spreading by Leo1

Verrier, Laure; Taglini, Francesca; Barrales, Ramón R.; Webb, Shaun; Urano, Takeshi; Braun, Sigurd; Bayne, Elizabeth H.

doi:10.1098/rsob.150045

Cited by 45 publications

(63 citation statements)

References 84 publications

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“…Our data show that RNA localization on chromatin is not sufficient to initiate RNAi-mediated heterochromatin formation. This indicates that mutations in the Paf1 complex, which promote establishment of ectopic RNAi-dependent heterochromatin, interfere with chromatin functions of the Paf1 complex rather than RNA release from chromatin (Sadeghi et al 2015;Verrier et al 2015).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Brönner¹,

Salvi²,

Zocco³

et al. 2017

Genome Res.

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“…Studies in metazoans and in fission yeast have also advanced our understanding of previously characterized Paf1C functions, such as the maintenance of heterochromatin and the regulation of alternative cleavage and polyadenylation of mRNAs [18–21]. Furthermore, several new Paf1C-regulated histone modifications have been described that illuminate our understanding of the role that Paf1C plays in modulating chromatin structure [21, 22].…”

Section: The Multifunctional Paf1 Complexmentioning

confidence: 99%

Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation

Oss

Cucinotta

Arndt

2017

Trends in Biochemical Sciences

140

130

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The conserved, multifunctional Paf1 complex (Paf1C) regulates all stages of the RNA polymerase II transcription cycle. In this review, we examine a diverse set of recent studies from various organisms that build on foundational studies in budding yeast. These studies identify new roles for Paf1C in the control of gene expression and the regulation of chromatin structure. In exploring these advances, we find that Paf1C’s various functions, such as the regulation of promoter-proximal pausing and development in higher eukaryotes, are complex and context-dependent. As more becomes known about the role of Paf1C in human disease, interest in the molecular mechanisms underpinning Paf1C function will continue to increase.

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“…Large-scale crosses by SGA were performed as described previously (Verrier et al 2015) using the Bioneer haploid deletion mutant library (version 3.0) and an imr1L(NcoI)::ura4 reporter strain that harbors an hphMX marker 2 kb upstream for selection. For analysis of the SGA data and epistasis calculation, see Supplemental Fig.…”

Section: Sga Analysesmentioning

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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Global regulation of heterochromatin spreading by Leo1

Cited by 45 publications

References 84 publications

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Accumulation of RNA on chromatin disrupts heterochromatic silencing

Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation

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

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