Three-Dimensional Genome Architecture: Players and Mechanisms
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Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Research Dioxin receptor and SLUG transcription factors regulate the insulator activity of B1 SINE retrotransposons via an RNA polymerase switch Angel Carlos Roma´n,1 Francisco J. Gonza´lez-Rico,1 Eduardo Molto´,2,3 Henar Hernando,4 Ana Neto,5 Cristina Vicente-Garcia,2,3 Esteban Ballestar,4 Jose´ L. Go´mez-Skarmeta,5 Jana Vavrova-Anderson,6 Robert J. White,6,7 Lluı´s Montoliu,2,3 and Pedro M. Ferna´ndez-Salguero1,8 1Departamento de Bioquı´mica y Biologı´a Molecular, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain; 2Centro Nacional de Biotecnologı´a (CNB), Consejo Superior de Investigaciones Cientı´ficas (CSIC), Department of Molecular and Cellular Biology, Campus de Cantoblanco, C/Darwin 3, 28049 Madrid, Spain; 3Centro de Investigacio´n Biome´dica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain; 4Chromatin and Disease Group, Cancer Epigenetics and Biology Programme, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona 08907, Spain; 5Centro Andaluz de Biologı´a del Desarrollo, CSIC-Universidad Pablo de Olavide, 41013 Sevilla, Spain; 6College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom; 7Beatson Institute for Cancer Research, Glasgow, G61 1BD, United Kingdom Complex genomes utilize insulators and boundary elements to help define spatial and temporal gene expression patterns. We report that a genome-wide B1 SINE (Short Interspersed Nuclear Element) retrotransposon (B1-X35S) has potent in- trinsic insulator activity in cultured cells and live animals. This insulation is mediated by binding of the transcription factors dioxin receptor (AHR) and SLUG (SNAI2) to consensus elements present in the SINE. -
Building the Interphase Nucleus: a Study on the Kinetics of 3D Chromosome Formation, Temporal Relation to Active Transcription, and the Role of Nuclear Rnas
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2020-07-28 Building the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs Kristin N. Abramo University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Bioinformatics Commons, Cell Biology Commons, Computational Biology Commons, Genomics Commons, Laboratory and Basic Science Research Commons, Molecular Biology Commons, Molecular Genetics Commons, and the Systems Biology Commons Repository Citation Abramo KN. (2020). Building the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs. GSBS Dissertations and Theses. https://doi.org/10.13028/a9gd-gw44. Retrieved from https://escholarship.umassmed.edu/ gsbs_diss/1099 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. BUILDING THE INTERPHASE NUCLEUS: A STUDY ON THE KINETICS OF 3D CHROMOSOME FORMATION, TEMPORAL RELATION TO ACTIVE TRANSCRIPTION, AND THE ROLE OF NUCLEAR RNAS A Dissertation Presented By KRISTIN N. ABRAMO Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSPOPHY July 28, 2020 Program in Systems Biology, Interdisciplinary Graduate Program BUILDING THE INTERPHASE NUCLEUS: A STUDY ON THE KINETICS OF 3D CHROMOSOME FORMATION, TEMPORAL RELATION TO ACTIVE TRANSCRIPTION, AND THE ROLE OF NUCLEAR RNAS A Dissertation Presented By KRISTIN N. -
Nuclear Bodies Reorganize During Myogenesis in Vitro and Are
Homma et al. Skeletal Muscle (2016) 6:42 DOI 10.1186/s13395-016-0113-7 RESEARCH Open Access Nuclear bodies reorganize during myogenesis in vitro and are differentially disrupted by expression of FSHD-associated DUX4 Sachiko Homma1, Mary Lou Beermann1, Bryant Yu1, Frederick M. Boyce2 and Jeffrey Boone Miller1,3* Abstract Background: Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD). However, questions remained about nuclear bodies in human myogenesis and in muscle disease. Methods: We examined nucleoli, PML bodies, SC35 speckles, TDP-43, and FUS in myoblasts and myotubes derived from healthy donors and from patients with FSHD, laminin-alpha-2-deficiency (MDC1A), and alpha-sarcoglycan- deficiency (LGMD2D). We further examined how these nuclear bodies and proteins were affected by DUX4-FL expression. Results: We found that nucleoli, PML bodies, and SC35 speckles reorganized during differentiation in vitro, with all three becoming less abundant in myotube vs. myoblast nuclei. In addition, though PML bodies did not change in size, both nucleoli and SC35 speckles were larger in myotube than myoblast nuclei. Similar patterns of nuclear body reorganization occurred in healthy control, MDC1A, and LGMD2D cultures, as well as in the large fraction of nuclei that did not show DUX4-FL expression in FSHD cultures. -
Nuclear Domains
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Cold Spring Harbor Laboratory Institutional Repository CELL SCIENCE AT A GLANCE 2891 Nuclear domains dynamic structures and, in addition, nuclear pore complex has been shown to rapid protein exchange occurs between have a remarkable substructure, in which David L. Spector many of the domains and the a basket extends into the nucleoplasm. Cold Spring Harbor Laboratory, One Bungtown nucleoplasm (Misteli, 2001). An The peripheral nuclear lamina lies Road, Cold Spring Harbor, NY 11724, USA extensive effort is currently underway by inside the nuclear envelope and is (e-mail: [email protected]) numerous laboratories to determine the composed of lamins A/C and B and is biological function(s) associated with thought to play a role in regulating Journal of Cell Science 114, 2891-2893 (2001) © The Company of Biologists Ltd each domain. The accompanying poster nuclear envelope structure and presents an overview of commonly anchoring interphase chromatin at the The mammalian cell nucleus is a observed nuclear domains. nuclear periphery. Internal patches of membrane-bound organelle that contains lamin protein are also present in the the machinery essential for gene The nucleus is bounded by a nuclear nucleoplasm (Moir et al., 2000). The expression. Although early studies envelope, a double-membrane structure, cartoon depicts much of the nuclear suggested that little organization exists of which the outer membrane is envelope/peripheral lamina as within this compartment, more contiguous with the rough endoplasmic transparent, so that internal structures contemporary studies have identified an reticulum and is often studded with can be more easily observed. -
Biogenesis of Nuclear Bodies
Downloaded from http://cshperspectives.cshlp.org/ on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Biogenesis of Nuclear Bodies Miroslav Dundr1 and Tom Misteli2 1Department of Cell Biology, Rosalind Franklin University of Medicine and Science, North Chicago, Ilinois 60064 2National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 Correspondence: [email protected]; [email protected] The nucleus is unique amongst cellular organelles in that it contains a myriad of discrete suborganelles. These nuclear bodies are morphologically and molecularly distinct entities, and they host specific nuclear processes. Although the mode of biogenesis appears to differ widely between individual nuclear bodies, several common design principles are emerging, particularly, the ability of nuclear bodies to form de novo, a role of RNA as a struc- tural element and self-organization as a mode of formation. The controlled biogenesis of nuclear bodies is essential for faithful maintenance of nuclear architecture during the cell cycle and is an important part of cellular responses to intra- and extracellular events. he mammalian cell nucleus contains a mul- seems to act indirectly by regulating the local Ttitude of discrete suborganelles, referred to concentration of its components in the nucleo- as nuclear bodies or nuclear compartments plasm. (reviewed in Dundr and Misteli 2001; Spector In many ways, nuclear bodies are similar 2001; Lamond and Spector 2003; Handwerger to conventional cellular organelles in the cy- and Gall 2006; Zhao et al. 2009). These bodies toplasm. Like cytoplasmic organelles, they con- are an essential part of the nuclear landscape tain a specific set of resident proteins, which as they compartmentalize the nuclear space defines each structure molecularly. -
Chromosome Territories
Downloaded from http://cshperspectives.cshlp.org/ on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Chromosome Territories Thomas Cremer1,2 and Marion Cremer1 1Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians- University, Grosshadernerstrasse 2, 82152 Martinsried, Germany 2Munich Center for Integrated Protein Sciences (CIPSM), 81377 Munich, Germany Correspondence: [email protected] Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenom- ics is considered, followed bya historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT archi- tecture, and of structural interactions with other CTs is provided as well as the dynamics of CT arrangements during cell cycle and postmitotic terminal differentiation. The article concludes with a discussion of open questions and new experimental strategies to answer them. mpressive progress has been achieved during for an integrated understanding of the structural Ithe last decade with regard to the functional and functional aspects of epigenetics with nu- implications of DNA methylation, histone mo- clear architecture during the differentiation of difications, and chromatin remodeling events toti- or pluripotent cells to functionally distinct for gene regulation (Fuks 2005; Kouzarides cell types. 2007; Maier et al. 2008; Jiang and Pugh 2009). The territorial organization of chromo- It has, however, also become obvious that somes in interphase (chromosome territories, decoding the chromatin language does not suf- CTs) constitutes a basic feature of nuclear archi- fice to fully understand the ways in which the tecture. -
The Role of ND10 Nuclear Bodies in Herpesvirus Infection: a Frenemy for the Virus?
viruses Review The Role of ND10 Nuclear Bodies in Herpesvirus Infection: A Frenemy for the Virus? Behdokht Jan Fada, Eleazar Reward and Haidong Gu * Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA; [email protected] (B.J.F.); [email protected] (E.R.) * Correspondence: [email protected]; Tel.: +1-313-577-6402 Abstract: Nuclear domains 10 (ND10), a.k.a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses. The diversity and dynamics of ND10 residents enable them to play seemingly opposite roles under different physiological conditions. Although the molecular mechanisms are not completely clear, the pro- and anti-cancer effects of ND10 have been well established in tumorigenesis. However, in herpesvirus research, until the recently emerged evidence of pro-viral contributions, ND10 nuclear bodies have been generally recognized as part of the intrinsic antiviral defenses that converge to the incoming viral DNA to inhibit the viral gene expression. In this review, we evaluate the newly discov- ered pro-infection influences of ND10 in various human herpesviruses and analyze their molecular foundation along with the traditional antiviral functions of ND10. We hope to shed light on the explicit role of ND10 in both the lytic and latent cycles of herpesvirus infection, which is imperative to the delineation of herpes pathogenesis and the development of prophylactic/therapeutic treatments for herpetic diseases. -
Chromatin Insulators and Topological Domains: Adding New Dimensions to 3D Genome Architecture
Genes 2015, 6, 790-811; doi:10.3390/genes6030790 OPEN ACCESS genes ISSN 2073-4425 www.mdpi.com/journal/genes Review Chromatin Insulators and Topological Domains: Adding New Dimensions to 3D Genome Architecture Navneet K. Matharu 1,* and Sajad H. Ahanger 2,* 1 Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA 2 Department of Ophthalmology, Lab for Retinal Cell Biology, University of Zurich, Wagistrasse 14, Zurich 8952, Switzerland * Authors to whom correspondence should be addressed; E-Mails: [email protected] (N.K.M.); [email protected] (S.H.A.). Academic Editor: Jessica Tyler Received: 8 June 2015 / Accepted: 20 August 2015 / Published: 1 September 2015 Abstract: The spatial organization of metazoan genomes has a direct influence on fundamental nuclear processes that include transcription, replication, and DNA repair. It is imperative to understand the mechanisms that shape the 3D organization of the eukaryotic genomes. Chromatin insulators have emerged as one of the central components of the genome organization tool-kit across species. Recent advancements in chromatin conformation capture technologies have provided important insights into the architectural role of insulators in genomic structuring. Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation. In this review, we will discuss the classical view and our renewed understanding of insulators as global genome organizers. We will also discuss the plasticity of chromatin structure and its re-organization during pluripotency and differentiation and in situations of cellular stress. -
Molecular Basis of the Function of Transcriptional Enhancers
cells Review Molecular Basis of the Function of Transcriptional Enhancers 1,2, 1, 1,3, Airat N. Ibragimov y, Oleg V. Bylino y and Yulii V. Shidlovskii * 1 Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia; [email protected] (A.N.I.); [email protected] (O.V.B.) 2 Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia 3 I.M. Sechenov First Moscow State Medical University, 8, bldg. 2 Trubetskaya St., 119048 Moscow, Russia * Correspondence: [email protected]; Tel.: +7-4991354096 These authors contributed equally to this study. y Received: 30 May 2020; Accepted: 3 July 2020; Published: 5 July 2020 Abstract: Transcriptional enhancers are major genomic elements that control gene activity in eukaryotes. Recent studies provided deeper insight into the temporal and spatial organization of transcription in the nucleus, the role of non-coding RNAs in the process, and the epigenetic control of gene expression. Thus, multiple molecular details of enhancer functioning were revealed. Here, we describe the recent data and models of molecular organization of enhancer-driven transcription. Keywords: enhancer; promoter; chromatin; transcriptional bursting; transcription factories; enhancer RNA; epigenetic marks 1. Introduction Gene transcription is precisely organized in time and space. The process requires the participation of hundreds of molecules, which form an extensive interaction network. Substantial progress was achieved recently in our understanding of the molecular processes that take place in the cell nucleus (e.g., see [1–9]). -
Nucleolus: a Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky
Nucleolus: A Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky To cite this version: Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, et al.. Nucleolus: A Central Hub for Nuclear Functions. Trends in Cell Biology, Elsevier, 2019, 29 (8), pp.647-659. 10.1016/j.tcb.2019.04.003. hal-02322927 HAL Id: hal-02322927 https://hal.archives-ouvertes.fr/hal-02322927 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Nucleolus: A Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky To cite this version: Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, et al.. Nucleolus: A Central Hub for Nuclear Functions. Trends in Cell Biology, Elsevier, 2019, 29 (8), pp.647-659. 10.1016/j.tcb.2019.04.003. hal-02322927 HAL Id: hal-02322927 https://hal.archives-ouvertes.fr/hal-02322927 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. -
Lncrna NEAT1 in Paraspeckles: a Structural Scaffold for Cellular DNA Damage Response Systems?
non-coding RNA Review LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems? Elisa Taiana 1,2,* , Domenica Ronchetti 1,2 , Katia Todoerti 2, Lucia Nobili 1 , Pierfrancesco Tassone 3, Nicola Amodio 3 and Antonino Neri 1,2,* 1 Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy; [email protected] (D.R.); [email protected] (L.N.) 2 Hematology, Fondazione Cà Granda IRCCS Policlinico, 20122 Milan, Italy; [email protected] 3 Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; [email protected] (P.T.); [email protected] (N.A.) * Correspondence: [email protected] (E.T.); [email protected] (A.N.); Tel.: +39-02-5032-0420 (E.T. & A.N.) Received: 5 June 2020; Accepted: 28 June 2020; Published: 1 July 2020 Abstract: Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases. Keywords: lncRNA; NEAT1; paraspeckle; DNA damage repair; cancer; neurodegenerative disease 1. -
A Subset of Drosophila Myc Sites Remain Associated with Mitotic Chromosomes Colocalized with Insulator Proteins
ARTICLE Received 16 Aug 2012 | Accepted 7 Jan 2013 | Published 12 Feb 2013 DOI: 10.1038/ncomms2469 A subset of Drosophila Myc sites remain associated with mitotic chromosomes colocalized with insulator proteins Jingping Yang1, Elizabeth Sung1, Paul G. Donlin-Asp1 & Victor G. Corces1 Myc has been characterized as a transcription factor that activates expression of genes involved in pluripotency and cancer, and as a component of the replication complex. Here we find that Myc is present at promoters and enhancers of Drosophila melanogaster genes during interphase. Myc colocalizes with Orc2, which is part of the prereplication complex, during G1. As is the case in mammals, Myc associates preferentially with paused genes, suggesting that it may also be involved in the release of RNA polymerase II from the promoter-proximal pausing in Drosophila. Interestingly, about 40% of Myc sites present in interphase persists during mitosis. None of the Myc mitotic sites correspond to enhancers, and only some correspond to promoters. The rest of the mitotic Myc sites overlap with binding sites for multiple insulator proteins that are also maintained in mitosis. These results suggest alternative mechanisms to explain the role of Myc in pluripotency and cancer. 1 Department of Biology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USA. Correspondence and requests for materials should be addressedto V.G.C. (email: [email protected]). NATURE COMMUNICATIONS | 4:1464 | DOI: 10.1038/ncomms2469 | www.nature.com/naturecommunications 1 & 2013 Macmillan Publishers Limited. All rights reserved. ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/ncomms2469 yc has been extensively studied as an oncogene that has Results critical roles in cancer initiation and metastasis of many Myc is present at the promoters of paused genes.