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| Open AccessThe HIV capsid mimics karyopherin engagement of FG-nucleoporins
Dissection of the nuclear pore complex provides a model in which the HIV capsid enters the nucleus through karyopherin mimicry, a mechanism likely to be conserved across other viruses.
- C. F. Dickson
- , S. Hertel
- & D. A. Jacques
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Article
| Open AccessRNA-mediated symmetry breaking enables singular olfactory receptor choice
Messenger RNAs transcribed from olfactory-receptor genes may have non-coding functions that include recruitment of transcriptional enhancers and inhibition of potentially thousands of competing alleles to ensure stable transcription of a single allele.
- Ariel D. Pourmorady
- , Elizaveta V. Bashkirova
- & Stavros Lomvardas
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Article
| Open AccessChromatin compartmentalization regulates the response to DNA damage
After the production of double-stranded breaks in mammalian cells, ATM drives the formation of the D compartment, which regulates DNA damage-responsive genes, through the clustering of damaged topologically associating domains, with a mechanism that is consistent with polymer–polymer phase separation.
- Coline Arnould
- , Vincent Rocher
- & Gaëlle Legube
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Article |
A viral biomolecular condensate coordinates assembly of progeny particles
Phase separation of the human adenovirus 52-kDa protein has an essential role in the formation of biomolecular condensates, regulating the coordinated assembly of viral progeny particles.
- Matthew Charman
- , Nicholas Grams
- & Matthew D. Weitzman
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Article |
Formin-mediated nuclear actin at androgen receptors promotes transcription
Functional mutations identified in patients with androgen insensitivity syndrome, in the formin and actin nucleator DAAM2, uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.
- Julian Knerr
- , Ralf Werner
- & Nadine C. Hornig
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Article |
MYC multimers shield stalled replication forks from RNA polymerase
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
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Article
| Open AccessHistone H2B.8 compacts flowering plant sperm through chromatin phase separation
H2B.8 is identified as a histone variant that mediates a newly described mechanism of transcription-compatible chromatin condensation in flowering plant sperm cells.
- Toby Buttress
- , Shengbo He
- & Xiaoqi Feng
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Article
| Open AccessNuclear chromosome locations dictate segregation error frequencies
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
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Article
| Open AccessMCM complexes are barriers that restrict cohesin-mediated loop extrusion
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
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Article
| Open AccessCell-type specialization is encoded by specific chromatin topologies
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
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Article
| Open AccessCold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression
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
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Article
| Open AccessHP1 drives de novo 3D genome reorganization in early Drosophila embryos
The heterochromatin protein HP1 has an essential role in establishing several features of the 3D nuclear organization of the genome during early embryonic development in Drosophila.
- Fides Zenk
- , Yinxiu Zhan
- & Nicola Iovino
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Article |
Integrated spatial genomics reveals global architecture of single nuclei
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
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Article |
RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops
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
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Article |
Cytoplasmic control of intranuclear polarity by human cytomegalovirus
Human cytomegalovirus rotates the nuclei of infected cells to set up intranuclear polarization and thereby separate viral DNA from inactive histones and associated host DNA.
- Dean J. Procter
- , Colleen Furey
- & Derek Walsh
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Article |
Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly
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
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Article |
Closed mitosis requires local disassembly of the nuclear envelope
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
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Article |
MeCP2 links heterochromatin condensates and neurodevelopmental disease
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
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Nucleolar RNA polymerase II drives ribosome biogenesis
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
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Composition-dependent thermodynamics of intracellular phase separation
Heterotypic multicomponent interactions are shown to dominate the liquid–liquid phase separation that enables the formation of intracellular condensates.
- Joshua A. Riback
- , Lian Zhu
- & Clifford P. Brangwynne
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Article |
LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation
Following cell division, phase separation of the transmembrane adaptor LEM2 ensures that the ESCRT machinery remodels microtubules and seals the nuclear envelope.
- Alexander von Appen
- , Dollie LaJoie
- & Adam Frost
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Article |
Convergent genes shape budding yeast pericentromeres
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
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Review Article |
Organization and regulation of gene transcription
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
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Letter |
Pol II phosphorylation regulates a switch between transcriptional and splicing condensates
RNA polymerase II with a hypophosphorylated C-terminal domain preferentially incorporates into mediator condensates, and with a hyperphosphorylated C-terminal domain into splicing-factor condensates, revealing phosphorylation as a regulatory mechanism in condensate preference.
- Yang Eric Guo
- , John C. Manteiga
- & Richard A. Young
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Article |
Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy
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
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Letter |
Genome–lamina interactions are established de novo in the early mouse embryo
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
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Letter |
Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei
MRG-1 indirectly promotes anchoring of chromatin in differentiated intestinal cells in Caenorhabditis elegans by sequestering the histone acetyltransferase CBP-1/p300.
- Daphne S. Cabianca
- , Celia Muñoz-Jiménez
- & Susan M. Gasser
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Review Article |
Transcription factors and 3D genome conformation in cell-fate decisions
Three-dimensional genome architecture has important roles in the regulation of gene expression and is therefore a key determinant of cell identity in normal development and in disease states.
- Ralph Stadhouders
- , Guillaume J. Filion
- & Thomas Graf
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Letter |
Sensory experience remodels genome architecture in neural circuit to drive motor learning
The authors identify a role for genome architecture reorganization in anterior dorsal cerebellar vermis granule neurons in learning a conditioned startle paradigm in mice.
- Tomoko Yamada
- , Yue Yang
- & Azad Bonni
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Letter |
Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors
Genetic deletion of mammalian chromatin remodelling complexes reveals that ISWI and SWI/SNF are required for binding of specific transcription factors and that ISWI regulates nucleosome positioning and nuclear organization in stem cells.
- Darko Barisic
- , Michael B. Stadler
- & Dirk Schübeler
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Article |
LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice
Specific interchromosomal contacts in olfactory sensory neurons form a super-enhancer that controls the expression of a single olfactory receptor in each neuron.
- Kevin Monahan
- , Adan Horta
- & Stavros Lomvardas
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Letter
| Open AccessGenome organization and DNA accessibility control antigenic variation in trypanosomes
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
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Article |
Nuclear ARP2/3 drives DNA break clustering for homology-directed repair
Polymerization of actin in the cell nucleus, promoted by the ARP2/3 complex, drives the clustering of double-strand DNA breaks into nuclear compartments where they can undergo homology-directed repair.
- Benjamin R. Schrank
- , Tomas Aparicio
- & Jean Gautier
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Article |
Nuclear F-actin and myosins drive relocalization of heterochromatic breaks
Relocalization of heterochromatic double-strand breaks to the nuclear periphery in Drosophila cells occurs via directed motions driven by nuclear actin filaments and myosins activated by the Smc5/6 complex.
- Christopher P. Caridi
- , Carla D’Agostino
- & Irene Chiolo
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Letter |
cGAS surveillance of micronuclei links genome instability to innate immunity
The cytoplasmic DNA sensor cGAS detects DNA in ruptured micronuclei and activates an innate immune response.
- Karen J. Mackenzie
- , Paula Carroll
- & Andrew P. Jackson
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Article |
Cell-cycle dynamics of chromosomal organization at single-cell resolution
Single-cell Hi-C analysis in thousands of mouse embryonic stem cells shows that chromosomal compartments, topological-associated domains and long-range loops all have distinct cell-cycle dynamics.
- Takashi Nagano
- , Yaniv Lubling
- & Amos Tanay
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Letter |
Phase separation drives heterochromatin domain formation
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
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Letter |
Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin
Phosphorylation or DNA binding promotes the physical partitioning of HP1α out of a soluble aqueous phase into droplets, suggesting that the repressive action of heterochromatin may in part be mediated by the phase separation of HP1.
- Adam G. Larson
- , Daniel Elnatan
- & Geeta J. Narlikar
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Letter |
Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl
The distribution of cohesin in the mouse genome depends on CTCF, transcription and the cohesin release factor Wapl.
- Georg A. Busslinger
- , Roman R. Stocsits
- & Jan-Michael Peters
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Letter |
Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition
Using a single-nucleus Hi-C protocol, the authors find that spatial organization of chromatin during oocyte-to-zygote transition differs between paternal and maternal nuclei within a single-cell zygote.
- Ilya M. Flyamer
- , Johanna Gassler
- & Kikuë Tachibana-Konwalski
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Article |
3D structures of individual mammalian genomes studied by single-cell Hi-C
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
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Article |
Complex multi-enhancer contacts captured by genome architecture mapping
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
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Letter |
The molecular architecture of lamins in somatic cells
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
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Letter |
Capturing pairwise and multi-way chromosomal conformations using chromosomal walks
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
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Letter |
Autophagy mediates degradation of nuclear lamina
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
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Article |
The C9orf72 repeat expansion disrupts nucleocytoplasmic transport
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
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Letter |
ESCRT-III controls nuclear envelope reformation
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
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Letter |
Nuclear architecture dictates HIV-1 integration site selection
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
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Letter |
Protein quality control at the inner nuclear membrane
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