Gene silencing articles within Nature Communications

Featured

  • Article
    | Open Access

    Argonaute proteins are loaded with small RNAs to confer target RNA specificity and proper gene silencing. Here, the authors establish that HRDE-2 recruits the unloaded nuclear Argonaute HRDE-1 to germ granules to facilitate correct small RNA loading.

    • Shihui Chen
    •  & Carolyn M. Phillips
  • Article
    | Open Access

    Through a genetic screen, the authors find that the cohesin regulator PDS5A is required for Polycomb target gene silencing. Derepression upon cohesin dysregulation is linked to loss of Polycomb loops without change in repressive chromatin domains.

    • Daniel Bsteh
    • , Hagar F. Moussa
    •  & Oliver Bell
  • Article
    | Open Access

    Small cell lung cancers (SCLC) have often inactivating mutations in RB1. In this study, the authors demonstrate that RB1 loss mediates low expression of YAP1 in SCLC tumors ultimately promoting metastasis and they propose to use benzamide family HDAC inhibitors to induce YAP1 expression for prevention of metastases.

    • Zhengming Wu
    • , Junhui Su
    •  & Kun-Liang Guan
  • Article
    | Open Access

    It has generally been considered that MOM1, a transcriptional silencing factor in plants, mediated silencing is independent or downstream of DNA methylation. Here, the authors show that MOM1 complex recruits the RdDM machinery through MORC6 to establish de novo DNA methylation in Arabidopsis.

    • Zheng Li
    • , Ming Wang
    •  & Steven E. Jacobsen
  • Article
    | Open Access

    The molecular mechanisms underlying androgen production in prostate cancer remain to be explored. Here, the authors reveal an epigenetic mark, K130Ac on H2A, following dual-phosphorylation on SREBP1 promoting de novo androgen synthesis to overcome the pharmacological inhibition of androgen synthesis.

    • Thanh Nguyen
    • , Dhivya Sridaran
    •  & Nupam P. Mahajan
  • Article
    | Open Access

    Delineating the specific role of Polycomb Repressive Complex 2 (PRC2) in various cancer systems is desirable as inhibitors for EZH2 inhibitors are approved for some cancers. Here the authors show haplo- and full-insufficiency of EZH2 drive divergent phenotypes in lung cancer. 3D tumoroids recapitulate transcriptional profiles, including FOXP2 derepression, and drug responses of in vivo tumors.

    • Fan Chen
    • , Aria L. Byrd
    •  & Christine Fillmore Brainson
  • Article
    | Open Access

    Here the authors show that a Polycomb Repressive Complex 1 (PRC1) containing PCGF1 prevents excessive loading of transcriptional activators and chromatin remodelers on nascent DNA, allowing proper deposition of nucleosomes immediately after the passage of the DNA replication fork to optimize downstream chromatin configurations in hematopoietic stem and progenitor cells (HSPCs).

    • Junichiro Takano
    • , Shinsuke Ito
    •  & Tomokatsu Ikawa
  • Article
    | Open Access

    Cold-induced silencing of Arabidopsis FLC requires the binding of VAL1 to an intronic motif. Here, the authors show that ASAP and PRC1, two interacting partner complexes of VAL1, mediate co-transcriptional repression and chromatin modulation to effectively co-ordinate different steps in FLC silencing.

    • Pawel Mikulski
    • , Philip Wolff
    •  & Caroline Dean
  • Article
    | Open Access

    In humans, the ovarian reserve is maintained over decades by meiotic arrest of oocytes. Here the authors show that Polycomb Repressive Complex 1 (PRC1)-mediated epigenetic programming is essential for formation of ovarian reserve and thus female reproductive lifespan.

    • Mengwen Hu
    • , Yu-Han Yeh
    •  & Satoshi H. Namekawa
  • Article
    | Open Access

    Cell fate commitment involves transcription factor activity and changes in chromatin architecture. Here the authors show that CAF-1 maintains lineage fidelity by controlling chromatin accessibility at specific sites; suppressing CAF-1 triggers differentiation of myeloid stem and progenitor cells into a mixed lineage state.

    • Reuben Franklin
    • , Yiming Guo
    •  & Sihem Cheloufi
  • Article
    | Open Access

    The ability to predict epigenetic regulation is an important challenge in biology. Here the authors describe heterochromatin nanodomains (HNDs) and compare four different types of H3K9me2/3-marked HNDs in mouse embryonic stem cells. They further develop a computational framework to predict genome-wide HND maps from DNA sequence and protein concentrations, at single-nucleotide resolution.

    • Graeme J. Thorn
    • , Christopher T. Clarkson
    •  & Vladimir B. Teif
  • Article
    | Open Access

    Female embryonic stem cells (ESCs) are the ideal model to study X chromosome inactivation (XCI) establishment; however, these cells are challenging to keep in culture. Here the authors create fluorescent ‘Xmas’ reporter mice as a renewable source of ESCs and show nucleosome remodelers Smarcc1 and Smarca4 create a nucleosome-free promoter region prior to the establishment of silencing.

    • Andrew Keniry
    • , Natasha Jansz
    •  & Marnie E. Blewitt
  • Article
    | Open Access

    The human silencing hub (HUSH) complex, which includes TASOR, deposits repressive marks on HIV proviruses, resulting in gene repression. Here, Matkovic et al. show that TASOR interacts with RNA Polymerase II, predominantly under its elongating state, and RNA degradation proteins to repress HIV provirus expression.

    • Roy Matkovic
    • , Marina Morel
    •  & Florence Margottin-Goguet
  • Article
    | Open Access

    Microsatellite instability (MSI), caused by deficiency of the DNA mismatch repair system, has been associated with improved response to immune checkpoint blockade (ICB). Here the authors show that inactivation of protein phosphatase 2A induces a MSI status, promoting cytotoxic T cell infiltration and response to ICB in pre-clinical cancer models.

    • Yu-Ting Yen
    • , May Chien
    •  & Shih-Chieh Hung
  • Article
    | Open Access

    How enhancers transition from a hypoacetylated primed state to a hyperacetylated-active state in response to differentiation stimuli is incompletely understood. Here the authors show that SETD5 forms a complex with NCoR-HDAC3 co-repressor to prevent histone acetylation of master adipogenic gene enhancers, while SETD5 degradation triggers enhancer hyperacetylation and transition to active state.

    • Yoshihiro Matsumura
    • , Ryo Ito
    •  & Juro Sakai
  • Article
    | Open Access

    Polycomb Repressive Complex 2, an important regulator of embryonic development, exists in two configurations, PRC2.1 and PRC2.2. Here the authors dissect the functional contributions of these two PRC2 subunits and observed complex-specific alterations in the cell state of pluripotent and early differentiating cells.

    • Chet H. Loh
    • , Siebe van Genesen
    •  & Gert Jan C. Veenstra
  • Article
    | Open Access

    The mammalian SWI/SNF nucleosome remodeler is required for spermatogenesis. Here, the authors show that PBAF is essential for meiotic cell division in males and required to activate the expression of critical genes involved in spindle assembly and nuclear division in spermatocytes.

    • Debashish U. Menon
    • , Oleksandr Kirsanov
    •  & Terry Magnuson
  • Article
    | Open Access

    Stochastic autosomal allele expression bias has been widely documented, yet the mechanisms behind this consequential phenomenon remain poorly understood. Here the authors show that the presence of introns greatly restricts monoallelic expression in a C. elegans model.

    • Bryan Sands
    • , Soo Yun
    •  & Alexander R. Mendenhall
  • Article
    | Open Access

    Polycomb repressive complexes (PRC1 and PRC2) repress genes that are crucial for development via epigenetic modifications; however, their role in differentiation is not well known. Here the authors reveal that a PCGF1-containing PRC1 variant facilitates exit from pluripotency by downregulating target genes and recruiting PRC2.

    • Hiroki Sugishita
    • , Takashi Kondo
    •  & Haruhiko Koseki
  • Article
    | Open Access

    The polycomb repressive complex 2 (PRC2) is a histone methyltransferase regulating cell differentiation and identity. Here, the authors show that the vertebrate-specific PRC2 accessory subunit PALI1 facilitates substrate binding by the complex and elucidate the allosteric mechanism of PALI1- mediated PRC2 activation.

    • Qi Zhang
    • , Samuel C. Agius
    •  & Chen Davidovich
  • Article
    | Open Access

    Globin loci harbor genes that are expressed embryonically and silenced postnatally. Here the authors show that zeta-globin silencing depends upon selective hypoacetylation of its TAD subdomain, which blocks its interaction with the alpha-globin super-enhancer, and zeta-globin can be reactivated by acetylation.

    • Andrew J. King
    • , Duantida Songdej
    •  & Christian Babbs
  • Article
    | Open Access

    Histone H3K9 methylation (H3K9me) states define repressed chromatin in eukaryotic cells. Here the authors reveal complete loss of all H3K9me in mammalian cells through successive deletion of H3K9 methyltransferase genes that results in the dissolution of heterochromatin and the derepression of nearly all repeat families.

    • Thomas Montavon
    • , Nicholas Shukeir
    •  & Thomas Jenuwein
  • Article
    | Open Access

    Stable epigenetic changes are relatively rare. Here the authors report that mating induces stable silencing of a single-copy transgene in C. elegans. Components of small RNA silencing are required for this stable silencing.

    • Sindhuja Devanapally
    • , Pravrutha Raman
    •  & Antony M. Jose
  • Article
    | Open Access

    DNA methylation targets CpG island promoters of germline genes to repress their expression in mouse somatic cells. Here the authors show that a transcription factor E2F6 is required to target CpG island DNA methylation and epigenetic silencing to germline genes during early mouse development.

    • Thomas Dahlet
    • , Matthias Truss
    •  & Michael Weber
  • Article
    | Open Access

    Pyruvate kinase phosphorylates histone H3T11 (H3pT11) and represses gene expression by forming a large complex SESAME (Serine-responsive SAM-containing Metabolic Enzyme). Here the authors show that SESAME-catalyzed H3pT11 regulates telomere silencing by promoting Sir2 binding at telomeres and preventing autophagy-mediated Sir2 degradation.

    • Shihao Zhang
    • , Xilan Yu
    •  & Shanshan Li
  • Article
    | Open Access

    Targeting chromatin regulators to a gene is emerging as powerful tool to control transcription. Here the authors demonstrate the use of nanobodies against chromatin regulators to control gene expression and epigenetic memory.

    • Mike V. Van
    • , Taihei Fujimori
    •  & Lacramioara Bintu
  • Article
    | Open Access

    Histone 3 Lys 27 trimethylation (H3K27me3) mediates epigenetic silencing of gene expression. Here, Zhang et al. show that in Arabidopsis, the BAH-domain H3K27me3-reader protein AIPP3 forms a complex with PHD proteins and CPL2, a plant-specific Pol II phosphatase, to inhibit Pol II activity by dephosphorylation.

    • Yi-Zhe Zhang
    • , Jianlong Yuan
    •  & Cheng-Guo Duan
  • Article
    | Open Access

    Epigenetically altered genes can have a key role in cancer pathobiology but epigenetic signatures that distinguish oncogenes are not yet known. Here, the authors identify broad genic repression domains, defined by widespread H3K27me3 modification, as an epigenetic signature to provide mutation-independent information for discovery of potential oncogenes.

    • Dongyu Zhao
    • , Lili Zhang
    •  & Kaifu Chen
  • Article
    | Open Access

    The HUSH complex plays a key role in controlling transcription of viruses and transposable elements. Here, the authors define the biochemical basis of HUSH assembly and show that the TASOR subunit contains a pseudo-PARP domain critical for HUSH-dependent transgene repression and H3K9me3 deposition over targets genome wide.

    • Christopher H. Douse
    • , Iva A. Tchasovnikarova
    •  & Yorgo Modis
  • Article
    | Open Access

    Mediator is a multiprotein complex required to activate gene transcription by RNAPII. Here, the authors report that MED12 and MED13 are conditional positive regulators that facilitate the expression of genes depleted in active chromatin marks and the induction of gene expression in response to environmental stimuli in Arabidopsis.

    • Qikun Liu
    • , Sylvain Bischof
    •  & Steven E. Jacobsen
  • Article
    | Open Access

    In fission yeast, several lncRNAs act in cis to regulate expression of adjacent genes. Here, the authors show that the conserved Pir2ARS2 protein is targeted, along with splicing factors, to cryptic introns in lncRNAs and recruits effectors, including RNAi machinery, for gene repression.

    • Gobi Thillainadesan
    • , Hua Xiao
    •  & Shiv I. S. Grewal
  • Article
    | Open Access

    ATRX is an RNA binding protein that mediates targeting of polycomb repressive complex 2 (PRC2) to genomic sites. Here the authors identify the RNA binding region and show that the RNA binding is required for ATRX localization and for its recruitment of PRC2 to a subset of polycomb targets.

    • Wenqing Ren
    • , Nicole Medeiros
    •  & Kavitha Sarma
  • Article
    | Open Access

    RNA is implicated in the targeting and function of Polycomb Group (PcG) chromatin regulators. Here the authors show that R-loops, three-stranded nucleic acid structures formed by DNA and RNA, are formed at some PcG binding sites in flies, as they are in mammals. Fly PRC2 can drive formation of RNA-DNA hybrids in vitro.

    • Célia Alecki
    • , Victoria Chiwara
    •  & Nicole J. Francis
  • Article
    | Open Access

    In Brassicaceae, interaction between the pollen-derived peptide ligand SP11 and the pistil-expressed receptor kinase SRK leads to self-incompatibility. Here the authors provide evidence that in Arabidopsis dominant self-compatibility inducers evolved at least twice via insertion of inverted repeats in the SRK locus.

    • Sota Fujii
    • , Hiroko Shimosato-Asano
    •  & Seiji Takayama
  • Article
    | Open Access

    RNA-directed DNA methylation (RdDM) is thought to silence newly inserted transposable elements (TEs) with RNA-independent mechanisms becoming more prominent as TEs age. Here, the authors show that RdDM continues to silence the oldest intact distal TEs in tomato and Arabidopsis suggesting a second, later phase of RdDM.

    • Zhengming Wang
    •  & David C. Baulcombe