Nuclear organization

  • Article
    | Open Access

    rDNA repeats residing in the nucleolus must be released to the nucleoplasm to allow repair by homologous recombination. Here the authors reveal insights into the molecular mechanism proposing that phosphorylation and SUMOylation of the rDNA-tethering complex facilitate the nucleolar release of damaged repeats to maintain genome integrity.

    • Matías Capella
    • , Imke K. Mandemaker
    •  & Sigurd Braun
  • Article
    | Open Access

    Transcriptional state plays a role in genome organization, however factors that link these processes are not well known. Here, the authors show Drosophila transcription factor Motif 1-binding protein (M1BP) interacts with the insulator protein CP190 to promote insulator function and activate Motif 1-dependent transcription at topologically associating domain (TAD) borders.

    • Indira Bag
    • , Shue Chen
    •  & Elissa P. Lei
  • Article
    | Open Access

    Recent advances in super-resolution microscopy have made it possible to measure chromatin 3D structure and transcription in thousands of single cells. Here, authors present a deep learning-based approach to characterise how chromatin structure relates to transcriptional state of individual cells and determine which structural features of chromatin regulation are important for gene expression state.

    • Aparna R. Rajpurkar
    • , Leslie J. Mateo
    •  & Alistair N. Boettiger
  • Article
    | Open Access

    Multi-layered epigenetic regulation in higher eukaryotes makes it challenging to disentangle the individual effects of modifications on chromatin structure and function. Here, the authors expressed mammalian DNA methyltransferases in yeast, which have no DNA methylation, to show that methylation has intrinsic effects on chromatin structure.

    • Diana Buitrago
    • , Mireia Labrador
    •  & Modesto Orozco
  • Article
    | Open Access

    How nuclear architecture overall affects the replication-timing programme is not yet clear. Here the authors reveal RIF1’s dual role as a chromatin-interaction scaffold and regulator of replication timing that allows the coordination of these two aspects of nuclear function.

    • Stefano Gnan
    • , Ilya M. Flyamer
    •  & Sara C. B. Buonomo
  • Article
    | Open Access

    The nuclear lamina bridges mechanical forces from the cytoskeleton to the nucleus, and while Lamin A/C is known to be crucial for this process, its regulation remains unclear. Here the authors show that levels of Lamin A/C scale with apico-basal compression of cells independently of tissue stiffness using Drosophila epithelial tissues and mammalian cells.

    • K. Venkatesan Iyer
    • , Anna Taubenberger
    •  & Frank Jülicher
  • Article
    | Open Access

    Secondary ion beam mass spectrometry (SIMS) is a method to obtain a chemical snapshot of biological tissue, but the spatial resolution is low. Here, the authors develop a computational and technology pipeline to localise a chemical signal in SIMS in 3D and sub-25 nm accuracy, called Ion Beam Tomography

    • Ahmet F. Coskun
    • , Guojun Han
    •  & Garry P. Nolan
  • Article
    | Open Access

    Hutchinson-Gilford progeria syndrome is a genetic disease where an aberrant form of Lamin A disrupts chromatin by interfering with lamina associated domains. Here, the authors present the SAMMY-seq, a method for genome-wide characterization of heterochromatin dynamics and detect early stage alterations of heterochromatin structure in progeria primary fibroblasts, accompained by Polycomb dysfunctions.

    • Endre Sebestyén
    • , Fabrizia Marullo
    •  & Chiara Lanzuolo
  • Article
    | Open Access

    Mechanical strength of in situ assembled nuclear lamin filaments arranged in a 3D meshwork is unclear. Here, using mechanical, structural and simulation tools, the authors report the hierarchical organization of the lamin meshwork that imparts strength and toughness to lamin filaments at par with silk and Kevlar®

    • K. Tanuj Sapra
    • , Zhao Qin
    •  & Ohad Medalia
  • Article
    | Open Access

    The role of cohesin in organizing a functional nuclear architecture remains poorly understood. Here the authors show that cohesin depleted cells pass through endomitosis forming a multilobulated nucleus able to proceed through S-phase with typical features of active and inactive nuclear compartments and spatio-temporal patterns of replication domains.

    • Marion Cremer
    • , Katharina Brandstetter
    •  & Thomas Cremer
  • Article
    | Open Access

    Firre encodes a lncRNA involved in nuclear organization in mammals. Here, the authors find that allelic deletion of Firre on the active X chromosome (Xa) results in dose-dependent loss of histone H3K27me3 on the inactive X chromosome (Xi), along with other trans-acting effects, including disruption of the perinuclear location and minor dysregulation of gene expression.

    • He Fang
    • , Giancarlo Bonora
    •  & Christine M. Disteche
  • Article
    | Open Access

    Chromatin loops bridging distant loci within chromosomes can be detected by a variety of techniques such as Hi-C. Here the authors present Chromosight, an algorithm applied on mammalian, bacterial, viral and yeast genomes, able to detect various types of pattern in chromosome contact maps, including chromosomal loops.

    • Cyril Matthey-Doret
    • , Lyam Baudry
    •  & Axel Cournac
  • Article
    | Open Access

    Mandibuloacral dysplasias (MADs) are rare progeroid syndromes characterized by nuclear morphological and functional abnormalities. Here the authors report that loss of mitochondrial membrane protein MTX2 causes a progeroid MAD sharing clinical features with lamin-associated progeroid syndromes.

    • Sahar Elouej
    • , Karim Harhouri
    •  & Annachiara De Sandre-Giovannoli
  • Article
    | Open Access

    mRNAs export from the nucleus is thought to be regulated in part by three nucleoporins that comprise the nuclear basket, but whether and how distinct basket nucleoporins interact with the RNA export machinery is unclear. Here, the authors use rapid auxin-mediated degradation of basket nucleoporins Nup153, Nup50, and Tpr, and see that Tpr interacts with the TREX-2 mRNA export complex.

    • Vasilisa Aksenova
    • , Alexandra Smith
    •  & Mary Dasso
  • Article
    | Open Access

    Meiosis-specific cohesins and the synaptonemal complex are essential for meiotic chromosome structure and function. Here the authors show that continued surveillance of these chromosome structures controls meiotic progression by regulating CHK-2, a master regulator of pairing and recombination.

    • Maikel Castellano-Pozo
    • , Sarai Pacheco
    •  & Enrique Martinez-Perez
  • Article
    | Open Access

    Common fragile sites are regions susceptible to replication stress and are prone to chromosomal instability. Here, the authors, by analyzing the contribution of 3D chromatin organization, identify and characterize a fragility signature and precisely map these fragility regions.

    • Dan Sarni
    • , Takayo Sasaki
    •  & Batsheva Kerem
  • Article
    | Open Access

    The relationship between regulatory elements, chromatin interactions and gene expression during development remains poorly understood. Here the authors present Tiled-C, a low-input 3C approach to study genome architecture at high resolution, and apply it to mouse erythroid differentiation in vivo, finding that enhancer-promoter interactions are formed gradually during differentiation, concomitant with progressive upregulation of gene activity.

    • A. Marieke Oudelaar
    • , Robert A. Beagrie
    •  & Jim R. Hughes
  • Article
    | Open Access

    The nuclear pore complex components, nucleoporins, have been proposed to mediate spatial and temporal organization of chromatin. Here, the authors show that Nucleoporin 153 interacts with CTCF and cohesin, and mediates their binding across cis-regulatory elements and TAD boundaries in mouse embryonic stem cells.

    • Shinichi Kadota
    • , Jianhong Ou
    •  & Eda Yildirim
  • Article
    | Open Access

    During cell migration, cells are polarized with distinct front vs. rear regions but whether and how polarity is transmitted to the nucleus is unclear. Here the authors show that frontally-biased endoplasmic reticulum and the nuclear membrane protein Emerin contribute to front-rear nuclear cell polarity.

    • Paulina Nastały
    • , Divya Purushothaman
    •  & Paolo Maiuri
  • Article
    | Open Access

    Temperature modulates plant development and environmental responses. Here, the authors show that increasing ambient temperature reduces the number of sub-nuclear photobodies in Arabidopsis by promoting selective disassembly of thermo-unstable photobodies in a manner dependent on phytochrome B’s photosensory module.

    • Joseph Hahm
    • , Keunhwa Kim
    •  & Meng Chen
  • Article
    | Open Access

    Genome dynamics allow cells to repair DNA double-strand breaks (DSBs), which are highly toxic DNA lesions. Here the authors reveal that in S. cerevisiae, Rad52 DNA repair proteins assemble in liquid droplets that work with dynamic nuclear microtubules to relocalize lesions to the nuclear periphery for repair.

    • Roxanne Oshidari
    • , Richard Huang
    •  & Karim Mekhail
  • Article
    | Open Access

    DNA double-strand breaks in ribosomal DNA repeats is associated with repression of ribosomal RNA synthesis. Here the authors reveal a cooperation between TOPBP1 and Treacle in the signaling cascade that triggers transcriptional inhibition and nucleolar segregation in response to rDNA breaks.

    • Clémence Mooser
    • , Ioanna-Eleni Symeonidou
    •  & Manuel Stucki
  • Article
    | Open Access

    Cell senescence involves stable arrest of cell proliferation and changes in gene expression and 3D genome reorganization. Here, the authors show that human condensin II complex participates in reorganization of the chromatin compartments, primarily through switching from heterochromatic B to euchromatic A compartments.

    • Osamu Iwasaki
    • , Hideki Tanizawa
    •  & Ken-ichi Noma
  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    •  & Jim R. Hughes
  • Article
    | Open Access

    FAT10 is an ubiquitin-like modifier that targets proteins to proteasomal degradation. Here, the authors show that FAT10 also regulates SUMO activation in vitro and in cells, providing evidence for functional crosstalk between two ubiquitin-like modifiers.

    • Annette Aichem
    • , Carolin Sailer
    •  & Marcus Groettrup
  • Article
    | Open Access

    HIV-1 usually targets active genes and integrates near the nuclear pore compartment. Here the authors show that recurrently targeted genes are proximal to super-enhancer genomic elements, which cluster in specific spatial compartments of the T cell nucleus, suggesting a role for nuclear organisation in viral infection.

    • Bojana Lucic
    • , Heng-Chang Chen
    •  & Marina Lusic
  • Article
    | Open Access

    Promyelocytic leukemia protein (PML) is the scaffolding protein that organizes PML nuclear bodies. Here the authors determine the crystal structure of a PML B1-box multimer and characterise the oligomerisation behaviour of the PML RBCC construct and show that disrupting B1-B1 interactions precludes promyelocytic leukemia leukemogenesis in transgenic mice.

    • Yuwen Li
    • , Xiaodan Ma
    •  & Guoyu Meng
  • Article
    | Open Access

    Lamins are intermediate filaments and the major component of the nuclear lamina. Here the authors determine the crystal structure of a construct comprising the N-terminal half of human lamin A/C and use their structure and cross-linking and biochemical experiments to discuss lamin assembly.

    • Jinsook Ahn
    • , Inseong Jo
    •  & Nam-Chul Ha
  • Article
    | Open Access

    The cellular functions of poly-SUMO chains of different compositions are not fully understood. Here, the authors characterize Arkadia/RNF111 as a SUMO-targeted ubiquitin ligase that recognizes proteins with hybrid SUMO1-capped SUMO2/3 chains and targets them for proteasomal degradation.

    • Annie M. Sriramachandran
    • , Katrin Meyer-Teschendorf
    •  & R. Jürgen Dohmen
  • Article
    | Open Access

    Torsins are unusual AAA + ATPases of unknown function that reside in the endoplasmic reticulum of all animals. Here the authors report that TorsinA forms tubular helical filaments with an unusual periodicity and that filamentous TorsinA directly interacts with membranes to form tubular protrusions.

    • F. Esra Demircioglu
    • , Weili Zheng
    •  & Thomas U. Schwartz
  • Article
    | Open Access

    Lamin A is critical for nuclear architecture but its structure and assembly are not fully understood. Here, the authors use quantitative cross-linking mass spectrometry to map intra- and intermolecular interactions within lamin homomers, providing insights into the molecular basis for lamin’s mechanical properties.

    • Alex A. Makarov
    • , Juan Zou
    •  & Eric C. Schirmer
  • Article
    | Open Access

    Eukaryotic genomes fold into topologically associated domains (TAD). Here the authors characterise a TAD regulatory architecture underlying lineage-specific gene regulation, finding that stripe TADs are associated with poised and active chromatin landscapes and linked to the cells functional state.

    • Christopher Barrington
    • , Dimitra Georgopoulou
    •  & Suzana Hadjur
  • Article
    | Open Access

    Rif1 is involved in different processes such as telomere homeostasis, DNA replication timing, and DNA double strand break (DSB) repair pathway choice. Here, the authors reveal that Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, attenuation of DNA end-resection, and DSB repair by non-homologous end-joining.

    • Gabriele A. Fontana
    • , Daniel Hess
    •  & Ulrich Rass
  • Article
    | Open Access

    Nuclear size scales with cell size, but the underlying mechanisms are unclear. Here, the authors report in fission yeast that the inner nuclear membrane protein Lem2 and the ER membrane protein Lnp1 are barriers to membrane flow and propose that they maintain nuclear size in proportion to cell membrane content.

    • Kazunori Kume
    • , Helena Cantwell
    •  & Paul Nurse
  • Article
    | Open Access

    Eukaryotic genomes are segregated into euchromatin and heterochromatin. Here the authors show that heterochromatin establishment during zebrafish embryo development is controlled by zygotic transcription of miR-430 and subsequent degradation of maternal transcripts encoding the chromatin remodeling protein Smarca2.

    • Kathrin Laue
    • , Srivarsha Rajshekar
    •  & Mary G. Goll
  • Article
    | Open Access

    The spatial organization of the genome plays an important but unclearly defined role in gene regulation. Here, the authors integrate Hi-C, RNA-seq and ATAC-seq data to map cardiogenesis from pluripotent stem cells and describe an RBM20-dependent splicing factory assembling the TTN locus with other RBM20 targets.

    • Alessandro Bertero
    • , Paul A. Fields
    •  & Charles E. Murry
  • Article
    | Open Access

    The role of the nuclear lamina (NL) in chromatin architecture is still poorly understood. Here, the authors provide evidence that disruption of the NL in Drosophila cells leads to overall chromatin compaction and repositioning from the nuclear envelope, whereas lamina-associated regions become less compacted and transcription within them is increased.

    • Sergey V. Ulianov
    • , Semen A. Doronin
    •  & Yuri Y. Shevelyov
  • Article
    | Open Access

    Transcription is globally repressed in early stage of embryo development, but a set of genes including pri-miR-430 and zinc finger genes is known to escape the repression. Here the authors image the very first transcriptional activities in the living zebra fish embryo, demonstrating a cell cycle-coordinated polymerase II transcription compartment.

    • Yavor Hadzhiev
    • , Haseeb K. Qureshi
    •  & Ferenc Müller