The LINC Complex Inhibits Excessive Chromatin Repression

We show here that the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is needed to minimize chromatin repression. The genomic binding profile of Polycomb, Heterochromatin Protein1 (HP1a) repressors, and of RNA-Pol II were studied in Drosophila larval muscles lacking functional LINC complex. A significant increase in the binding of Polycomb, and parallel reduction of RNA-Pol-II binding to a set of muscle genes was observed. Consistently, enhanced tri-methylated H3K9 and H3K27 repressive modifications, and reduced chromatin activation by H3K9 acetylation were found. Furthermore, larger tri-methylated H3K27me3 repressive clusters, and chromatin redistribution from the nuclear periphery towards nuclear center, were detected in live LINC mutant larval muscles. Computer simulation indicated that the observed dissociation of the chromatin from the nuclear envelope promotes growth of tri-methylated H3K27 repressive clusters. Thus, we suggest that by promoting chromatin-nuclear envelope binding, the LINC complex restricts the size of repressive H3K27 tri-methylated clusters, thereby limiting the binding of Polycomb transcription repressor, directing robust transcription in muscle fibers.

• Publication year

  2022

• Venue

  bioRxiv

• Publication date

  2022-02-10

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/cells12060932PMID 36980273PMCID 10047284
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Regulation of chromatin microphase separation by binding of protein complexes

  2023cited by this paper
• Polymer dynamics relates chromosome mixing to temporal changes in biological contact maps

  2022cited by this paper
• Regulation of chromatin microphase separation by adsorbed protein complexes

  2022cited by this paper
• H3K27me3 at pericentromeric heterochromatin is a defining feature of the early mouse blastocyst

  2022cited by this paper
• Live imaging of chromatin distribution reveals novel principles of nuclear architecture and chromatin compartmentalization

  2021influential reference
• The LINC Between Mechanical Forces and Chromatin

  2021cited by this paper
• Nuclear deformation guides chromatin reorganization in cardiac development and disease

  2021cited by this paper
• Intranuclear mesoscale viscoelastic changes during osteoblastic differentiation of human mesenchymal stem cells

  2021cited by this paper
• Emerin self-assembly and nucleoskeletal coupling regulate nuclear envelope mechanics against stress

  2021cited by this paper
• H4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensable for inducing gene silencing

  2021cited by this paper
• Mechanical Regulation of Transcription: Recent Advances.

  2021cited by this paper
• Recruitment of BAF to the nuclear envelope couples the LINC complex to endoreplication

  2020cited by this paper
• Mesoscale phase separation of chromatin in the nucleus

  2020influential reference
• The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

  2020influential reference
• A minimal constraint device for imaging nuclei in live Drosophila contractile larval muscles reveals novel nuclear mechanical dynamics.

  2020cited by this paper
• A Balance Between Intermediate Filaments and Microtubules Maintains Nuclear Architecture in the Cardiomyocyte

  2019cited by this paper
• Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

  2019cited by this paper
• Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation

  2019cited by this paper
• Emerging views of the nucleus as a cellular mechanosensor

  2018cited by this paper
• Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho

  2018cited by this paper
• Condensin II drives large-scale folding and spatial partitioning of interphase chromosomes in Drosophila nuclei

  2018cited by this paper
• Mechanotransduction via the LINC complex regulates DNA replication in myonuclei

  2018cited by this paper
• Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation

  2018cited by this paper
• Sequential activities of Dynein, Mud and Asp in centrosome–spindle coupling maintain centrosome number upon mitosis

  2017cited by this paper
• Chromatin state changes during neural development revealed by in vivo cell-type specific profiling

  2017cited by this paper
• The three-dimensional genome organization of Drosophila melanogaster through data integration

  2017influential reference
• mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

  2017cited by this paper
• The LINC complex contributes to heterochromatin organisation and transcriptional gene silencing in plants

  2017cited by this paper
• Genome Regulation by Polycomb and Trithorax: 70 Years and Counting.

  2017cited by this paper
• lmerTest Package: Tests in Linear Mixed Effects Models

  2017cited by this paper
• Cross talk between the cytoplasm and nucleus during development and disease.

  2016cited by this paper
• Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment

  2016cited by this paper
• Mechanically Induced Chromatin Condensation Requires Cellular Contractility in Mesenchymal Stem Cells.

  2016cited by this paper
• Mechanostimulation Promotes Nuclear and Epigenetic Changes in Oligodendrocytes

  2016cited by this paper
• Cell-type-specific profiling of protein–DNA interactions without cell isolation using targeted DamID with next-generation sequencing

  2016cited by this paper
• Long-Range Chromatin Interactions.

  2015cited by this paper
• Nesprin provides elastic properties to muscle nuclei by cooperating with spectraplakin and EB1

  2015cited by this paper
• damidseq_pipeline: an automated pipeline for processing DamID sequencing datasets

  2015cited by this paper
• Accessorizing and anchoring the LINC complex for multifunctionality

  2015cited by this paper
• LINC complex proteins in development and disease.

  2014cited by this paper
• BoxPlotR: a web tool for generation of box plots

  2014cited by this paper
• Nesprins in health and disease.

  2014cited by this paper
• Cell-Type-Specific Profiling of Gene Expression and Chromatin Binding without Cell Isolation: Assaying RNA Pol II Occupancy in Neural Stem Cells

  2013cited by this paper
• Connecting the nucleus to the cytoskeleton by SUN-KASH bridges across the nuclear envelope.

  2013cited by this paper
• Acetylation of the SUN protein Mps3 by Eco1 regulates its function in nuclear organization

  2012cited by this paper
• Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules

  2012influential reference
• The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing

  2012cited by this paper
• LINC complexes form by binding of three KASH peptides to domain interfaces of trimeric SUN proteins.

  2012cited by this paper
• The changing faces of HP1: From heterochromatin formation and gene silencing to euchromatic gene expression

  2011cited by this paper
• The SUUR protein is involved in binding of SU(VAR)3–9 and methylation of H3K9 and H3K27 in chromosomes of Drosophila melanogaster

  2011cited by this paper
• Integrative Genomics Viewer

  2011cited by this paper
• LINC complexes in health and disease

  2010cited by this paper
• UvA-DARE ( Digital Academic Repository ) Reading the maps : Organization and function of chromatin types in Drosophila Braunschweig

  2010cited by this paper
• Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections

  2009cited by this paper
• Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice.

  2009cited by this paper
• On the roles of the Drosophila KASH domain proteins Msp-300 and Klarsicht

  2008cited by this paper
• Drosophila klaroid Encodes a SUN Domain Protein Required for Klarsicht Localization to the Nuclear Envelope and Nuclear Migration in the Eye

  2007cited by this paper
• High-Resolution Mapping Reveals Links of HP1 with Active and Inactive Chromatin Components

  2007cited by this paper
• Stabilization of chromatin structure by PRC1, a Polycomb complex.

  1999cited by this paper
• Fast parallel algorithms for short-range molecular dynamics

  1993cited by this paper

• Tumor peripheral stiffness modulates lenvatinib resistance in HCC preclinical models by regulating FIS1-dependent mitophagy

  2025cites this paper
• MeCP2-driven chromatin organization controls nuclear stiffness

  2025influential citation
• Chromatin organization controls nuclear stiffness

  2025cites this paper
• The role of inner nuclear membrane protein emerin in myogenesis

  2025cites this paper
• Nuclear deformability depends on H3K9-methylated heterochromatin anchorage to the nuclear periphery in Caenorhabditis elegans

  2025cites this paper
• Complex topologies in phase separated droplets predicted from universal phase diagram

  2025cites this paper
• The Dual Roles of Lamin A/C in Macrophage Mechanotransduction

  2024cites this paper
• Data‐Driven and Cell‐Specific Determination of Nuclei‐Associated Actin Structure

  2024cites this paper
• Lamins: The backbone of the nucleocytoskeleton interface.

  2024cites this paper
• Polymer physics view of peripheral chromatin: de Gennes' self-similar carpet.

  2024cites this paper
• Anchorage of H3K9-methylated heterochromatin to the nuclear periphery helps mediate P-cell nuclear migration though constricted spaces in Caenorhabditis elegans

  2024cites this paper
• A computational pipeline for identifying gene targets and signalling pathways in cancer cells to improve lymphocyte infiltration and immune checkpoint therapy efficacy

  2024cites this paper
• Recent insights in striated muscle laminopathies

  2024cites this paper
• Data driven and cell specific determination of nuclei-associated actin structure

  2023cites this paper
• Histone Modification of Osteogenesis Related Genes Triggered by Substrate Topography Promotes Human Mesenchymal Stem Cell Differentiation

  2023cites this paper