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Open AccessJournal ArticleDOI

Noncoding RNA and Polycomb recruitment

Neil Brockdorff
- 01 Apr 2013 - 
- Vol. 19, Iss: 4, pp 429-442
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TLDR
The evidence for and against this hypothesis for direct interaction between PRC2 proteins and the different ncRNAs are discussed, in the process highlighting alternative models and discussing experiments that will help to resolve existing discrepancies.
Abstract
A plethora of noncoding (nc) RNAs has been revealed through the application of high-throughput analysis of the transcriptome, and this has led to an intensive search for possible biological functions attributable to these transcripts. A major category of functional ncRNAs that has emerged is for those that are implicated in coordinate gene silencing, either in cis or in trans. The archetype for this class is the well-studied long ncRNA Xist which functions in cis to bring about transcriptional silencing of an entire X chromosome in female mammals. An important step in X chromosome inactivation is the recruitment of the Polycomb repressive complex PRC2 that mediates histone H3 lysine 27 methylation, a hallmark of the inactive X chromosome, and recent studies have suggested that this occurs as a consequence of PRC2 interacting directly with Xist RNA. Accordingly, other ncRNAs have been linked to PRC2 targeting either in cis or in trans, and here also the mechanism has been proposed to involve direct interaction between PRC2 proteins and the different ncRNAs. In this review, I discuss the evidence for and against this hypothesis, in the process highlighting alternative models and discussing experiments that, in the future, will help to resolve existing discrepancies.

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lincRNAs: genomics, evolution, and mechanisms.

TL;DR: This Review outlines the emerging understanding of lincRNAs in vertebrate animals, with emphases on how they are being identified and current conclusions and questions regarding their genomics, evolution and mechanisms of action.
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RNA-mediated epigenetic regulation of gene expression

TL;DR: These co-transcriptional silencing mechanisms form powerful RNA surveillance systems that detect and silence inappropriate transcription events, and provide a memory of these events via self-reinforcing epigenetic loops.
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Histone Deacetylase Inhibitors as Anticancer Drugs.

TL;DR: Different classes of HDAC inhibitors, mechanisms of their actions and novel results of preclinical and clinical studies are summarized, including the combination with other therapeutic modalities are discussed.
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Transcriptional regulation by Polycomb group proteins.

TL;DR: The current knowledge of the PRC complexes is discussed, how they are targeted to chromatin and how the high diversity of the PcG proteins allows these complexes to influence cell identity.
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Mechanisms of long noncoding RNA function in development and disease

TL;DR: Examples illustrating the versatility of lncRNAs in gene control, development and differentiation, as well as in human disease are discussed.
References
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Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

TL;DR: To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
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Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs

TL;DR: The transcriptional landscape of the four human HOX loci is characterized at five base pair resolution in 11 anatomic sites and 231 HOX ncRNAs are identified that extend known transcribed regions by more than 30 kilobases, suggesting transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance.
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Gene Action in the X -chromosome of the Mouse ( Mus musculus L.)

TL;DR: Ohno and Hauschka1 showed that in female mice one chromosome of mammary carcinoma cells and of normal diploid cells of the ovary, mammary gland and liver was heteropyKnotic and suggested that the so-called sex chromatin was composed of one heteropyknotic X-chromosome.
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Molecular Mechanisms of Long Noncoding RNAs

TL;DR: These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution.
Journal ArticleDOI

Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing

TL;DR: The purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex, is reported, and it is demonstrated that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27).
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