Gene silencing articles within Nature

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  • Article
    | Open Access

    Experiments in mice show that designed epigenome editors that contain domains of transcriptional repressors can enable stable epigenetic silencing of Pcsk9, a gene with a role in cholesterol homeostasis, without inducing DNA breaks.

    • Martino Alfredo Cappelluti
    • , Valeria Mollica Poeta
    •  & Angelo Lombardo

  • Article
    | Open Access

    A study describes the molecular basis of sexual development of Toxoplasma gondii entirely in vitro, demonstrating the role and interaction of AP2XII-1 and AP2XI-2 in the developmental program of this protozoan parasite.

    • Ana Vera Antunes
    • , Martina Shahinas
    •  & Mohamed-Ali Hakimi

  • Article |

    A high throughput recruitment assay testing the transcriptional activity of more than 100,000 protein fragments tiling across most human chromatin regulators and transcription factors maps the locations and strengths of activation, repression and bifunctional domains, and identifies the sequences necessary for these functions.

    • Nicole DelRosso
    • , Josh Tycko
    •  & Lacramioara Bintu

  • Article
    | Open Access

    The structures of single COOLAIR RNA isoforms change in abundance and shape in response to external conditions; structural mutation of these isoforms altered FLC expression and flowering time, consistent with a regulatory role of the COOLAIR structure in FLC transcription.

    • Minglei Yang
    • , Pan Zhu
    •  & Yiliang Ding

  • Article |

    Following global DNA demethylation, mouse gonadal primordial germ cells undergo remodelling of repressive chromatin modifications, resulting in a sex-specific signature that is required to safeguard the transcriptional program.

    • Tien-Chi Huang
    • , Yi-Fang Wang
    •  & Petra Hajkova

  • Article
    | Open Access

    In Arabidopsis thaliana, downregulation of the floral repressor FLC in response to cold occurs through a mechanism in which the FLC activator FRIGIDA is sequestered into biomolecular condensates away from the FLC promoter.

    • Pan Zhu
    • , Clare Lister
    •  & Caroline Dean

  • Article |

    Fission yeast grown in sublethal levels of caffeine develop heterochromatin-dependent epimutations conferring unstable heritable gene silencing that conveys resistance to caffeine, while remaining genetically wild type.

    • Sito Torres-Garcia
    • , Imtiyaz Yaseen
    •  & Robin C. Allshire

  • Article |

    The DNA modification N6-methyladenine regulates gene expression during mouse trophoblast development by depositing at the boundaries of active chromatin and preventing its spread by antagonizing the chromatin organizer SATB1.

    • Zheng Li
    • , Shuai Zhao
    •  & Andrew Z. Xiao

  • Article |

    In Caenorhabditis elegans, the ribonucleotidyltransferase RDE-3 adds alternating uridine and guanosine ribonucleotides to the 3′ termini of RNAs, a key step in RNA interference and thus epigenetic inheritance in the C. elegans germline.

    • Aditi Shukla
    • , Jenny Yan
    •  & Scott Kennedy

  • Article |

    ZNFX-1 and WAGO-4 localize to germ granules in early Caenorhabditis elegans embryogenesis and later separate to form independent liquid-like droplets, and the temporal and spatial ordering of these droplets may help cells to organize complex RNA processing pathways.

    • Gang Wan
    • , Brandon D. Fields
    •  & Scott Kennedy

  • Letter |

    The fission yeast is shown to have a mechanism to prevent small RNAs from inducing heterochromatin and epigenetic gene silencing; this protective model involves the highly conserved Paf1 complex, which is known to promote transcription and processing of pre-mRNA, and protects protein-coding genes from unwanted silencing by spurious transcripts.

    • Katarzyna Maria Kowalik
    • , Yukiko Shimada
    •  & Marc Bühler

  • Letter |

    The RING finger protein TRIM37 is encoded by a gene that is amplified in certain breast cancers, but its function is unknown; here, it is shown to mono-ubiquitinate histone H2A and repress gene expression, and to function as a breast cancer oncoprotein.

    • Sanchita Bhatnagar
    • , Claude Gazin
    •  & Michael R. Green

  • Letter |

    The transcriptions of frq sense and antisense RNAs are mutually inhibitory and form a double negative feedback loop required for robust and sustained circadian rhythmicity: antisense transcription inhibits sense expression by causing chromatin modifications and premature transcription termination.

    • Zhihong Xue
    • , Qiaohong Ye
    •  & Yi Liu

  • Letter |

    The human fungal pathogen Mucor circinelloides develops spontaneous resistance to an antifungal drug both through mutation and through a newly identified epigenetic RNA-mediated pathway; RNA interference is spontaneously triggered to silence the fkbA gene, giving rise to drug-resistant epimutants that revert to being drug-sensitive once again when grown in the absence of drug.

    • Silvia Calo
    • , Cecelia Shertz-Wall
    •  & Joseph Heitman

  • Article |

    This study uses zinc-finger nucleases to target an inducible XIST transgene into chromosome 21 from trisomic Down’s syndrome pluripotent stem cells; the XIST RNA coats one copy of chromosome 21 and triggers whole chromosome silencing, suggesting the potential of this approach for studying chromosomal disorders such as Down’s syndrome and for research into gene therapies.

    • Jun Jiang
    • , Yuanchun Jing
    •  & Jeanne B. Lawrence

  • Letter |

    The Polycomb repressive complex 1 (PRC1) is found to have important gene-dosage-dependent and sex-specific roles in primordial germ cell (PGC) development, including the maintenance of high levels of Oct4 and Nanog and ensuring the proper timing of meiosis through the suppression of retinoic acid signalling in female PGCs.

    • Shihori Yokobayashi
    • , Ching-Yeu Liang
    •  & Antoine H. F. M. Peters

  • Letter |

    In the fission yeast Schizosaccharomyces pombe RNA interference (RNAi) machinery promotes heterochromatin assembly and silencing of centromeric repeats; here it is shown that RNAi participates in silencing other genomic regions, such as sexual differentiation genes and retrotransposons, and this process is regulated by developmental and environmental signals.

    • Soichiro Yamanaka
    • , Sameet Mehta
    •  & Shiv I. S. Grewal

  • Letter |

    Nuclear-retained transcripts containing expanded repeats are shown to be sensitive to antisense silencing, and in a transgenic mouse model of myotonic dystrophy type 1, systemic administration of ASOs causes a rapid knockdown of the toxic RNA in skeletal muscle, correcting some hallmark features of the disease.

    • Thurman M. Wheeler
    • , Andrew J. Leger
    •  & Charles A. Thornton

  • Letter |

    The histone modification H3K9me3, the histone methyltransferase SUV39H1 and the H3K9me3-binding protein HP1α participate in maintaining the silent state of the two canonical T helper 1 cell signature genes (which encode interferon-γ and T-bet), ensuring T helper 2 lineage stability in vitro and in vivo; targeting this pathway has the potential to reduce asthma-related pathology.

    • Rhys S. Allan
    • , Elina Zueva
    •  & Sebastian Amigorena

  • News & Views |

    Mutations in the maternal copy of the UBE3A gene cause a neurodevelopmental disorder known as Angelman syndrome. Drugs that activate the normally silenced paternal copy of this gene may be of therapeutic value. See Letter p.185

    • Arthur L. Beaudet

  • Article |

    Adenovirus E1B-55k targets transcription factor p53 for degradation and is thought to be critical for p53 inactivation during adenovirus replication. Indeed, mutant viruses lacking E1B-55k have been tested as viral cancer therapies selective for p53-positive tumours. These authors find another adenoviral protein, E4-ORF3, to inactivate p53 independently of E1B-55k by means of a chromatin-silencing mechanism that prevents access of p53 to its DNA target sites.

    • Conrado Soria
    • , Fanny E. Estermann
    •  & Clodagh C. O’Shea

  • Letter |

    A diploid organism has two copies of each gene, one inherited from each parent. The expression levels of the two alleles can be biased by dominant/recessive relationships. In Brassica, self-incompatibility in pollen is determined by dominance relationships between the two alleles of the gene SP11; the recessive allele is methylated and hence silenced. Here it is shown that such methylation is controlled by a small non-coding RNA encoded in the flanking region of the dominant allele.

    • Yoshiaki Tarutani
    • , Hiroshi Shiba
    •  & Seiji Takayama

  • Letter |

    The ability of retrotransposons to mobilize and insert into genes presents a challenge to a cell needing to maintain its genomic integrity. These authors have studied retrotransposition in embryonic carcinoma-derived cells. On insertion into DNA, the retrotransposon is quickly silenced, but the retrotransposon-specificity of this process implies that multiple silencing mechanisms may exist. Once cells differentiate, the ability to silence newly introduced retrotransposons is lost but previously inactivated retrotransposons remain inactive.

    • Jose L. Garcia-Perez
    • , Maria Morell
    •  & John V. Moran

  • Letter |

    Polycomb group (PcG) proteins are transcriptional repressors that modify chromatin and regulate important developmental genes. One PcG-associated, chromatin-modifying activity is an enzyme that ubiquitinates histone H2A of chromatin. Here, a fruitfly PcG complex that is associated with H2A deubiquitination, and thereby with gene repression, is identified. PcG-mediated gene silencing might thus involve a dynamic balance between ubiquitination and deubiquitination of H2A.

    • Johanna C. Scheuermann
    • , Andrés Gaytán de Ayala Alonso
    •  & Jürg Müller

  • Article |

    Induced pluripotent stem cells (iPSCs) are generated by the enforced expression of particular transcription factors in somatic cells. The extent to which such cells are equivalent to embryonic stem (ES) cells is an open question. Here, genetically identical mouse ES cells and iPSCs have been compared; the overall expression patterns of messenger RNAs and microRNAs are the same, with the exception of a few transcripts encoded within an imprinted gene cluster on chromosome 12qF1.

    • Matthias Stadtfeld
    • , Effie Apostolou
    •  & Konrad Hochedlinger

  • News |

    Tiny particles carrying short strands of RNA can interfere with protein production in tumours.

    • Janet Fang

  • Letter |

    Female gametes in flowering plants develop from a meiotic division of a precursor cell followed by mitotic divisions of one of the resulting haploid cells to yield the gametophyte. Here, ARGONAUTE 9 (AGO9) — a protein involved in RNA interference — is identified as a factor required for specification of the gametophyte. AGO9 is found not in the cell destined to be the gametophyte, but in the neighbouring companion cells, suggesting that it functions in a non-cell-autonomous manner.

    • Vianey Olmedo-Monfil
    • , Noé Durán-Figueroa
    •  & Jean-Philippe Vielle-Calzada

  • Letter |

    Endogenous retroviruses (ERVs) are widely dispersed in mammalian genomes, and are silenced in somatic cells by DNA methylation. Here, an ERV silencing pathway independent of DNA methylation is shown to operate in embryonic stem cells. The pathway involves the histone H3K9 methyltransferase ESET and might be important for ERV silencing during the stages in embryogenesis when DNA methylation is reprogrammed.

    • Toshiyuki Matsui
    • , Danny Leung
    •  & Yoichi Shinkai

  • Letter |

    Much of the mammalian genome is derived from retroelements, a significant proportion of which are endogenous retroviruses (ERVs). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation, but the initiators of this process are largely unknown. Here, deletion of KAP1 is shown to lead to a marked upregulation of a range of ERVs in mouse embryonic stem cells and in early embryos.

    • Helen M. Rowe
    • , Johan Jakobsson
    •  & Didier Trono

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