Nuclear organization

  • Article |

    MYC dissociation from active promoters alters its interactions with proteins involved in transcription termination and RNA processing, influencing DNA repair and thus, potentially, tumour cell growth.

    • Daniel Solvie
    • , Apoorva Baluapuri
    •  & Martin Eilers
  • Article
    | Open Access

    Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, chromosomes are shown to have different segregation error frequencies that result in non-random aneuploidy landscapes.

    • Sjoerd J. Klaasen
    • , My Anh Truong
    •  & Geert J. P. L. Kops
  • Article
    | Open Access

    Single-nucleus Hi-C of embryos, polymer simulations and single-molecule imaging collectively reveal that MCM complexes influence genome folding and gene expression by impeding DNA loop extrusion.

    • Bart J. H. Dequeker
    • , Matthias J. Scherr
    •  & Kikuë Tachibana
  • Article
    | Open Access

    A new technique called immunoGAM, which combines genome architecture mapping (GAM) with immunoselection, enabled the discovery of specialized chromatin conformations linked to gene expression in specific cell populations from mouse brain tissues.

    • Warren Winick-Ng
    • , Alexander Kukalev
    •  & Ana Pombo
  • 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 |

    Multiplexed imaging of 3,660 chromosomal loci in individual mouse embryonic stem cells by DNA seqFISH+ with immunofluorescence of 17 chromatin marks and subnuclear structures reveals invariant organization of loci within individual cells, and heterogeneous and long-lived distinct combinatorial chromatin states in cellular subpopulations.

    • Yodai Takei
    • , Jina Yun
    •  & Long Cai
  • Article |

    Telomeric-repeat-containing RNA is recruited to telomeres by a mechanism that involves the DNA recombinase RAD51 and the formation of DNA–RNA hybrids, or R-loops—a process similar to that involved in homology-directed DNA repair.

    • Marianna Feretzaki
    • , Michaela Pospisilova
    •  & Joachim Lingner
  • Article |

    The surfactant-like protein Ki-67 mediates the clustering of chromosomes during mitotic exit, which displaces large cytoplasmic molecules from the future nuclear space and thus enables the separation of cytoplasmic and nuclear components before the nuclear envelope reforms.

    • Sara Cuylen-Haering
    • , Mina Petrovic
    •  & Daniel W. Gerlich
  • Article |

    In a study performed in Schizosaccharomyces pombe, ‘closed mitosis’ is shown to occur via local disassembly of the nuclear envelope within the narrow bridge connecting segregating daughter nuclei, and a key role is identified for Les1, which restricts nuclear envelope breakdown to the bridge.

    • Gautam Dey
    • , Siân Culley
    •  & Buzz Baum
  • Article |

    The chromatin protein MeCP2 is a component of dynamic, liquid-like heterochromatin condensates, and the ability of MeCP2 to form condensates is disrupted by mutations in the MECP2 gene that occur in the neurodevelopmental disorder Rett syndrome.

    • Charles H. Li
    • , Eliot L. Coffey
    •  & Richard A. Young
  • Article |

    RNA polymerase II has an unexpected function in the nucleolus, helping to drive the expression of ribosomal RNA and to protect nucleolar structure through a mechanism involving triplex R-loop structures.

    • Karan J. Abraham
    • , Negin Khosraviani
    •  & Karim Mekhail
  • Article |

    The three-dimensional structure of pericentromeres in budding yeast is defined by convergent genes, which mark pericentromere borders and trap cohesin complexes loaded at centromeres, generating an architecture that allows correct chromosome segregation.

    • Flora Paldi
    • , Bonnie Alver
    •  & Adele L. Marston
  • Review Article |

    Structural and microscopy studies of gene transcription underpin a model in which phosphorylation controls the shuttling of RNA polymerase II between promoter and gene-body condensates to regulate transcription initiation and elongation.

    • Patrick Cramer
  • Article |

    A disease model using cardiomyocytes derived from induced pluripotent stem cells of patients with mutated LMNA-related dilated cardiomyopathy reveals that the abnormal activation of the PDGF pathway is associated with the arrhythmic phenotypes of patients.

    • Jaecheol Lee
    • , Vittavat Termglinchan
    •  & Joseph C. Wu
  • Letter |

    Spatial genome organization into lamina-associated domains is first established in the mouse zygote immediately after fertilization without inheritance from the maternal germline—with the paternal and maternal pronucleus exhibiting different organization, which subsequently converges prior to implantation of the embryo.

    • Máté Borsos
    • , Sara M. Perricone
    •  & Jop Kind
  • Letter
    | Open Access

    Long-read sequencing allows the assembly of antigen-gene arrays in Trypanosoma brucei and, coupled with deletion experiments, demonstrates that histone variants act as a molecular link between genome architecture, chromatin conformation and antigen variation.

    • Laura S. M. Müller
    • , Raúl O. Cosentino
    •  & T. Nicolai Siegel
  • Letter |

    HP1a can nucleate into foci that display liquid properties during the early stages of heterochromatin domain formation in Drosophila embryos, suggesting that the repressive action of heterochromatin may be mediated in part by emergent properties of phase separation.

    • Amy R. Strom
    • , Alexander V. Emelyanov
    •  & Gary H. Karpen
  • Article |

    A chromosome conformation capture method in which single cells are first imaged and then processed enables intact genome folding to be studied at a scale of 100 kb, validated, and analysed to generate hypotheses about 3D genomic interactions and organisation.

    • Tim J. Stevens
    • , David Lando
    •  & Ernest D. Laue
  • Article |

    A technique called genome architecture mapping (GAM) involves sequencing DNA from a large number of thin nuclear cryosections to develop a map of genome organization without the limitations of existing 3C-based methods.

    • Robert A. Beagrie
    • , Antonio Scialdone
    •  & Ana Pombo
  • Letter |

    Cryo-electron tomography reveals a detailed view of the structural organization of the lamin meshwork within the lamina of the mammalian cell nucleus.

    • Yagmur Turgay
    • , Matthias Eibauer
    •  & Ohad Medalia
  • Letter |

    A conformation capture sequencing method is developed to link multiple genomic loci into three-dimensional proximity chains called chromosomal walks (C-walks), adding to our understanding of how higher-order chromosomal structures participate in genome regulation.

    • Pedro Olivares-Chauvet
    • , Zohar Mukamel
    •  & Amos Tanay
  • Letter |

    In response to cancer-associated stress, autophagy machinery mediates degradation of nuclear lamina components in mammals, suggesting that cells might degrade nuclear components to prevent tumorigenesis.

    • Zhixun Dou
    • , Caiyue Xu
    •  & Shelley L. Berger
  • Article |

    A candidate-based genetic screen in Drosophila expressing 30 G4C2-repeat-containing RNAs finds that RanGAP, a key regulator of nucleocytoplasmic transport, is a potent suppressor of neurodegeneration; the defects caused by the G4C2 repeat expansions can be rescued with antisense oligonucleotides or small molecules targeting the G-quadruplexes.

    • Ke Zhang
    • , Christopher J. Donnelly
    •  & Jeffrey D. Rothstein
  • Letter |

    The ESCRT-III complex is implicated in the reformation of the nuclear envelope; the CHMP2A component of ESCRT-III is directed to the forming nuclear envelope through classical ESCRT-assembly mechanisms, with the help of the p97 complex component UFD1, and provides an activity essential for nuclear envelope reformation.

    • Yolanda Olmos
    • , Lorna Hodgson
    •  & Jeremy G. Carlton
  • Letter |

    HIV-1 integration into the host cell genome occurs in the outer shell of the nucleus in close correspondence with the nuclear pore, in which a series of cellular genes are preferentially targeted by the virus.

    • Bruna Marini
    • , Attila Kertesz-Farkas
    •  & Marina Lusic
  • Letter |

    A protein degradation pathway is found at the inner nuclear membrane that is distinct from, but complementary to, endoplasmic-reticulum-associated protein degradation, and which is mediated by the Asi protein complex; a genome-wide library screening of yeast identifies more than 20 substrates of this pathway, which is shown to target mislocalized integral membrane proteins for degradation.

    • Anton Khmelinskii
    • , Ewa Blaszczak
    •  & Michael Knop
  • Letter
    | Open Access

    A study of DNA replication timing in mouse and human cells reveals that replication domains (domains of the genome which replicate at the same time) share a correlation with topologically associating domains; these results reconcile cell-type-specific sub-nuclear compartmentalization with developmentally stable chromosome domains and offer a unified model for large scale chromosome structure and function.

    • Benjamin D. Pope
    • , Tyrone Ryba
    •  & David M. Gilbert
  • Letter |

    Genome-wide chromatin conformation capture (Hi-C) is used to investigate three-dimensional genome organization in Schizosaccharomyces pombe; small domains of chromatin interact locally on chromosome arms to form globules, which depend on cohesin but not heterochromatin for formation, and heterochromatin at centromeres and telomeres provides crucial structural constraints to shape genome architecture.

    • Takeshi Mizuguchi
    • , Geoffrey Fudenberg
    •  & Shiv I. S. Grewal
  • Letter |

    The POU homeodomain transcription factor Pit1 is required for pituitary development; here Pit1-occupied enhancers are shown to interact with the nuclear architecture components matrin-3 and Satb1, and this association is required for activation of Pit1-regulated enhancers and coding target genes.

    • Dorota Skowronska-Krawczyk
    • , Qi Ma
    •  & Michael G. Rosenfeld
  • Article |

    Structurally polymorphic C9orf72 hexanucleotide repeats cause an impairment in transcriptional processivity and lead to accumulation of truncated repeat-containing transcripts that bind to specific ribonucleoproteins, such as nucleolin, in a conformation-dependent manner resulting in nucleolar stress and C9orf72-linked pathology in amyotrophic lateral sclerosis and frontotemporal dementia.

    • Aaron R. Haeusler
    • , Christopher J. Donnelly
    •  & Jiou Wang
  • Letter |

    A chromatin interaction analysis with paired-end tagging (ChIA-PET) approach is used to delineate chromatin interactions mediated by RNA polymerase II in several different stem-cell populations; putative long-range promoter–enhancer interactions are inferred, indicating that linear juxtaposition does not necessarily guide enhancer target selection and prevalent cell-specific enhancer usage.

    • Yubo Zhang
    • , Chee-Hong Wong
    •  & Chia-Lin Wei
  • Letter |

    Using 4C technology, higher-order topological features of the pluripotent genome are identified; in pluripotent stem cells, Nanog clusters specifically with other pluripotency genes and this clustering is centred around Nanog-binding sites, suggesting that Nanog helps to shape the three-dimensional structure of the pluripotent genome and thereby contributes to the robustness of the pluripotent state.

    • Elzo de Wit
    • , Britta A. M. Bouwman
    •  & Wouter de Laat