Chromosome Structure and Organisation
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Insights Into Hp1a-Chromatin Interactions
cells Review Insights into HP1a-Chromatin Interactions Silvia Meyer-Nava , Victor E. Nieto-Caballero, Mario Zurita and Viviana Valadez-Graham * Instituto de Biotecnología, Departamento de Genética del Desarrollo y Fisiología Molecular, Universidad Nacional Autónoma de México, Cuernavaca Morelos 62210, Mexico; [email protected] (S.M.-N.); [email protected] (V.E.N.-C.); [email protected] (M.Z.) * Correspondence: [email protected]; Tel.: +527773291631 Received: 26 June 2020; Accepted: 21 July 2020; Published: 9 August 2020 Abstract: Understanding the packaging of DNA into chromatin has become a crucial aspect in the study of gene regulatory mechanisms. Heterochromatin establishment and maintenance dynamics have emerged as some of the main features involved in genome stability, cellular development, and diseases. The most extensively studied heterochromatin protein is HP1a. This protein has two main domains, namely the chromoshadow and the chromodomain, separated by a hinge region. Over the years, several works have taken on the task of identifying HP1a partners using different strategies. In this review, we focus on describing these interactions and the possible complexes and subcomplexes associated with this critical protein. Characterization of these complexes will help us to clearly understand the implications of the interactions of HP1a in heterochromatin maintenance, heterochromatin dynamics, and heterochromatin’s direct relationship to gene regulation and chromatin organization. Keywords: heterochromatin; HP1a; genome stability 1. Introduction Chromatin is a complex of DNA and associated proteins in which the genetic material is packed in the interior of the nucleus of eukaryotic cells [1]. To organize this highly compact structure, two categories of proteins are needed: histones [2] and accessory proteins, such as chromatin regulators and histone-modifying proteins. -
Distinct Visual Pathways Mediatedrosophilalarval Light
The Journal of Neuroscience, April 27, 2011 • 31(17):6527–6534 • 6527 Behavioral/Systems/Cognitive Distinct Visual Pathways Mediate Drosophila Larval Light Avoidance and Circadian Clock Entrainment Alex C. Keene,1 Esteban O. Mazzoni,1 Jamie Zhen,1 Meg A. Younger,1 Satoko Yamaguchi,1 Justin Blau,1 Claude Desplan,1 and Simon G. Sprecher1,2 1Department of Biology, Center for Developmental Genetics, New York University, New York, New York 10003-6688, and 2Department of Biology, Institute of Cell and Developmental Biology, University of Fribourg, 1700 Fribourg, Switzerland Visual organs perceive environmental stimuli required for rapid initiation of behaviors and can also entrain the circadian clock. The larval eye of Drosophila is capable of both functions. Each eye contains only 12 photoreceptors (PRs), which can be subdivided into two subtypes. Four PRs express blue-sensitive rhodopsin5 (rh5) and eight express green-sensitive rhodopsin6 (rh6). We found that either PR-subtype is sufficient to entrain the molecular clock by light, while only the Rh5-PR subtype is essential for light avoidance. Acetylcholine released from PRs confers both functions. Both subtypes of larval PRs innervate the main circadian pacemaker neurons of the larva, the neuropeptide PDF (pigment-dispersing factor)-expressing lateral neurons (LNs), providing sensory input to control circadian rhythms. How- ever, we show that PDF-expressing LNs are dispensable for light avoidance, and a distinct set of three clock neurons is required. Thus we have identifieddistinctsensoryandcentralcircuitryregulatinglightavoidancebehaviorandclockentrainment.Ourfindingsprovideinsightsintothe coding of sensory information for distinct behavioral functions and the underlying molecular and neuronal circuitry. Introduction sin6 (rh6) (Sprecher et al., 2007; Sprecher and Desplan, 2008). -
Genome Analysis and Knowledge
Dahary et al. BMC Medical Genomics (2019) 12:200 https://doi.org/10.1186/s12920-019-0647-8 SOFTWARE Open Access Genome analysis and knowledge-driven variant interpretation with TGex Dvir Dahary1*, Yaron Golan1, Yaron Mazor1, Ofer Zelig1, Ruth Barshir2, Michal Twik2, Tsippi Iny Stein2, Guy Rosner3,4, Revital Kariv3,4, Fei Chen5, Qiang Zhang5, Yiping Shen5,6,7, Marilyn Safran2, Doron Lancet2* and Simon Fishilevich2* Abstract Background: The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient’s phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. Results: We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex’s main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex’s broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards’ recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters. -
The Nature of Genomes Viral Genomes Prokaryotic Genome
The nature of genomes • Genomics: study of structure and function of genomes • Genome size – variable, by orders of magnitude – number of genes roughly proportional to genome size • Plasmids – symbiotic DNA molecules, not essential – mostly circular in prokaryotes • Organellar DNA – chloroplast, mitochondrion – derived by endosymbiosis from bacterial ancestors Chapter 2: Genes and genomes © 2002 by W. H. Freeman and Company Chapter 2: Genes and genomes © 2002 by W. H. Freeman and Company Viral genomes • Nonliving particle In prokaryotes, viruses are – nucleic acid sometimes referred to as – protein bacteriophages. • DNA or RNA – single-stranded or double-stranded – linear or circular • Compact genomes with little spacer DNA Chapter 2: Genes and genomes © 2002 by W. H. Freeman and Company Chapter 2: Genes and genomes © 2002 by W. H. Freeman and Company Prokaryotic genome • Usually circular double helix – occupies nucleoid region of cell – attached to plasma membrane • Genes are close together with little intergenic spacer • Operon – tandem cluster of coordinately regulated genes – transcribed as single mRNA • Introns very rare Chapter 2: Genes and genomes © 2002 by W. H. Freeman and Company Chapter 2: Genes and genomes © 2002 by W. H. Freeman and Company 1 Eukaryotic nuclear genomes • Each species has characteristic chromosome number • Genes are segments of nuclear chromosomes • Ploidy refers to number of complete sets of chromosomes –haploid (1n): one complete set of genes – diploid (2n) – polyploid (≥3n) • In diploids, chromosomes come in homologous pairs (homologs) In humans, somatic cells have – structurally similar 2n = 46 chromosomes. – same sequence of genes – may contain different alleles Chapter 2: Genes and genomes © 2002 by W. H. -
Metabolic Inactivation of the Circadian Transmitter, Pigment Dispersing Factor (PDF), by Neprilysin-Like Peptidases in Drosophila R
4465 The Journal of Experimental Biology 210, 4465-4470 Published by The Company of Biologists 2007 doi:10.1242/jeb.012088 Metabolic inactivation of the circadian transmitter, pigment dispersing factor (PDF), by neprilysin-like peptidases in Drosophila R. Elwyn Isaac1,*, Erik C. Johnson2, Neil Audsley3 and Alan D. Shirras4 1Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK, 2Department of Biology, Wake Forest University, NC, USA, 3Central Science Laboratory, Sand Hutton, York, YO41 1LZ, UK and 4Department of Biological Sciences, University of Lancaster, LA1 4YQ, UK *Author for correspondence (e-mail: [email protected]) Accepted 4 October 2007 Summary Recent studies have firmly established pigment confirming that such cleavage results in PDF inactivation. dispersing factor (PDF), a C-terminally amidated The Ser7–Leu8 peptide bond was also the principal octodecapeptide, as a key neurotransmitter regulating cleavage site when PDF was incubated with membranes rhythmic circadian locomotory behaviours in adult prepared from heads of adult Drosophila. This Drosophila melanogaster. The mechanisms by which PDF endopeptidase activity was inhibited by the neprilysin –1 functions as a circadian peptide transmitter are not fully inhibitors phosphoramidon (IC50, 0.15·mol·l ) and –1 understood, however; in particular, nothing is known thiorphan (IC50, 1.2·mol·l ). We propose that cleavage by about the role of extracellular peptidases in terminating a member of the Drosophila neprilysin family of PDF signalling at synapses. In this study we show that PDF endopeptidases is the most likely mechanism for is susceptible to hydrolysis by neprilysin, an endopeptidase inactivating synaptic PDF and that neprilysin might have that is enriched in synaptic membranes of mammals and an important role in regulating PDF signals within insects. -
Visualization of Chromatin Folding Patterns in Chicken Erythrocytes by Atomic Force Microscopy (AFM)
Cell Research (1997), 7, 143-150 Visualization of chromatin folding patterns in chicken erythrocytes by atomic force microscopy (AFM) 1 QIAN RUO LAN ZHENG XIA LIU, MEI YUN ZHOU, HEN YUE XIE, CHU JIANG, ZHI JIANG YAN Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China LI MIN QIAN, YI ZHANG, JUN HU Shanghai Institute of Nuclear Research, Chinese Academy of Sciences, Shanghai 201800, China ABSTRACT The organization of the higher order structure of chro- matin in chicken erythrocytes has been examined with tapping-mode scanning force microscopy under conditions close to their native environment. Reproducible high- resolution AFM images of chromatin compaction at seve- ral levels can be demonstrated. An extended beads-on-a- string (width of ~ 15-20nm, height of ~ 2-3nm for each individual nucleosome) can be consistently observed. Fur- thermore, superbeads (width of ~ 40nm, height of ~ 7nm) are demonstrated. Visualization of the solenoid conforma- tion at the level of 30nm chromatin fiber is attained either by using AFM or by using electron microscopy. In addi- tion, tightly coiled chromatin fibers (~ 50-60nm and ~ 90- ll0nm) can be revealed. Our data suggest that the chro- matin in the interphase nucleus of chicken erythrocyte rep- resents a high-order conformation and AFM provides use- ful high-resolution structural information concerning the folding pattern of interphase chromatin fibers. Key words: The chromatin folding pattern, chicken erythrocyte, atomic force microscopy. 1. To whom correspondence should be addressed: Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. 143 The chromatin folding patterns in chicken erythrocytes by AFM INTRODUCTION Owing to the tremendous packing density and folding complexity in mitotic chro- mosomes, analysis of chromosome architecture has recently focused on interphase chromatin structure. -
The Origin of the Eukaryotic Cell Based on Conservation of Existing
The Origin of the Eukaryotic Albert D. G. de Roos The Beagle Armada Cell Based on Conservation Bioinformatics Division of Existing Interfaces Einsteinstraat 67 3316GG Dordrecht, The Netherlands [email protected] Abstract Current theories about the origin of the eukaryotic Keywords cell all assume that during evolution a prokaryotic cell acquired a Evolution, nucleus, eukaryotes, self-assembly, cellular membranes nucleus. Here, it is shown that a scenario in which the nucleus acquired a plasma membrane is inherently less complex because existing interfaces remain intact during evolution. Using this scenario, the evolution to the first eukaryotic cell can be modeled in three steps, based on the self-assembly of cellular membranes by lipid-protein interactions. First, the inclusion of chromosomes in a nuclear membrane is mediated by interactions between laminar proteins and lipid vesicles. Second, the formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the expression of intrinsic membrane proteins. Third, a plasma membrane is formed by fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three self-assembly processes occur both in vivo and in vitro. This new model provides a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell and suggests an inherent ability of an ancestral, primitive genome to induce its own inclusion in a membrane. 1 Introduction The origin of eukaryotes is one of the major challenges in evolutionary cell biology. No inter- mediates between prokaryotes and eukaryotes have been found, and the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. There are basically two competing classes of hypotheses: the endosymbiotic and the autogenic. -
The Physics of Chromatin
The physics of chromatin Helmut Schiessel Max-Planck-Institut f¨ur Polymerforschung, Theory Group, P.O.Box 3148, D-55021 Mainz, Germany Abstract. Recent progress has been made in the understanding of the physical properties of chromatin – the dense complex of DNA and histone proteins that occupies the nuclei of plant and animal cells. Here I will focus on the two lowest levels of the hierarchy of DNA folding into the chromatin complex: (i) the nucleosome, the chromatin repeating unit consisting of a globular aggregate of eight histone proteins with the DNA wrapped around: its overcharging, the DNA unwrapping transition, the ”sliding” of the octamer along the DNA. (ii) The 30nm chromatin fiber, the necklace- like structure of nucleosomes connected via linker DNA: its geometry, its mechanical properties under stretching and its response to changing ionic conditions. I will stress that chromatin combines two seemingly contradictory features: (1) high compaction of DNA within the nuclear envelope and at the same time (2) accessibility to genes, promoter regions and gene regulatory sequences. Contents 1 Introduction 3 2 Single nucleosome 8 2.1 Experimentalfactsonthecoreparticle . 8 2.2 Polyelectrolyte–charged sphere complexes as model systems for the nucleosome 11 2.2.1 Single-sphere complex (highly charged case) . 12 2.2.2 Multi-sphere complex (highly charged case) . 14 2.2.3 Weaklychargedcase ......................... 16 2.2.4 Physiological conditions . 20 arXiv:cond-mat/0303455v1 [cond-mat.soft] 21 Mar 2003 2.3 Unwrappingtransition............................ 23 2.3.1 Instabilities of the nucleosome core particle at low and at high ionic strength 23 2.3.2 The rosette state at high ionic strength . -
Analysis of 3D Genomic Interactions Identifies Candidate Host Genes That Transposable Elements Potentially Regulate Ramya Raviram1,2,3†, Pedro P
Raviram et al. Genome Biology (2018) 19:216 https://doi.org/10.1186/s13059-018-1598-7 RESEARCH Open Access Analysis of 3D genomic interactions identifies candidate host genes that transposable elements potentially regulate Ramya Raviram1,2,3†, Pedro P. Rocha1,4†, Vincent M. Luo1,2, Emily Swanzey5, Emily R. Miraldi2,6,7,8, Edward B. Chuong9, Cédric Feschotte10, Richard Bonneau2,6,7 and Jane A. Skok1* Abstract Background: The organization of chromatin in the nucleus plays an essential role in gene regulation. About half of the mammalian genome comprises transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation. Results: Using PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of transposable element interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach, we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual transposable element insertions that interact with and potentially regulate target genes. -
Lecture No. VII Title of Topic: - Architecture of Chromosome Prepared By- Vinod Kumar, Assistant Professor, (PB & G) College of Agriculture, Powarkheda
Course: Fundamentals of Genetics Class: - Ist Year, IInd Semester Lecture No. VII Title of topic: - Architecture of Chromosome Prepared by- Vinod Kumar, Assistant Professor, (PB & G) College of Agriculture, Powarkheda Introduction:- E. Strasburger in 1875 first discovered thread-like structures which appeared during cell division. These thread like structures were called chromosomes due to their affinity for basic dyes. The term chromosome is derived from two Greek words; chrom = colour, soma=body. This term was first used by Waldeyer in 1888. Morphology: The outer covering or sheath of a chromosome is known as pellicle, which encloses the matrix. Within the matrix lies the chromatin. Flemming introduced the term chromatin in 1879. The term chromatin refers to the Feulgen positive materials observed in interphase nucleus and later during nuclear division. Chromatin readily stains with basic dyes especially Basic Fuchsin, which is specific for DNA which in turn is a major constituent of chromosomes. The chromosome morphology changes during cell division and mitotic metaphase is the most suitable stage for studies on chromosome morphology. In mitotic metaphase chromosomes, the following structural features can be seen under the light microscope. 1. Chromatid: Each metaphase chromosome appears to be longitudinally divided into two identical parts each of which is called chromatid. Both the chromatids of a chromosome appear to be joined together at a point known as centromere. The two chromatids of chromosome separate from each other during mitotic anaphase (and during anaphase II of meiosis) and move towards opposite poles. Since the two chromatids making up a chromosome are produced through replication of a single chromatid during synthesis (S) phase of interphase, they are referred to as sister chromatids. -
Reverse Transcriptase Activity Innate to DNA Polymerase I and DNA
Reverse transcriptase activity innate to DNA SEE COMMENTARY polymerase I and DNA topoisomerase I proteins of Streptomyces telomere complex Kai Bao*† and Stanley N. Cohen*‡§ Departments of *Genetics and ‡Medicine, Stanford University School of Medicine, Stanford, CA 94305-5120 Edited by Nicholas R. Cozzarelli, University of California, Berkeley, CA, and approved August 10, 2004 (received for review June 18, 2004) Replication of Streptomyces linear chromosomes and plasmids gation and, remarkably, that both of these eubacterial enzymes -proceeds bidirectionally from a central origin, leaving recessed 5 can function efficiently as RTs in addition to having the bio termini that are extended by a telomere binding complex. This chemical properties predicted from their sequences. We further complex contains both a telomere-protecting terminal protein show that the Streptomyces coelicolor and Streptomyces lividans (Tpg) and a telomere-associated protein that interacts with Tpg TopA proteins are prototypes for a subfamily of bacterial and the DNA ends of linear Streptomyces replicons. By using topoisomerases whose catalytic domains contain a unique Asp– histidine-tagged telomere-associated protein (Tap) as a scaffold, Asp doublet motif that is required for their RT activity and which we identified DNA polymerase (PolA) and topoisomerase I (TopA) is essential also to the RNA-dependent DNA polymerase func- proteins as other components of the Streptomyces telomere com- tions of HIV RT and eukaryotic cell telomerases (16, 17). plex. Biochemical characterization of these proteins indicated that both PolA and TopA exhibit highly efficient reverse transcriptase Materials and Methods (RT) activity in addition to their predicted functions. Although RT Plasmid and Bacterial Strains. -
On the Positions of Centromeres in Chicken Lampbrush Chromosomes
Chromosome Research (2006) 14:777–789 # Springer 2006 DOI: 10.1007/s10577-006-1085-y On the positions of centromeres in chicken lampbrush chromosomes Alla Krasikova, Svetlana Deryusheva, Svetlana Galkina, Anna Kurganova, Andrei Evteev & Elena Gaginskaya* Biological Research Institute, Saint-Petersburg State University, Oranienbaumskoie sch. 2, Stary Peterhof, Saint-Petersburg, 198504, Russia; Tel: +7-812-4507311; Fax: +7-812-4507310; E-mail: [email protected] *Correspondence Received 5 May 2006. Received in revised form and accepted for publication by Mary Delany 24 July 2006 Key words: centromere, chicken, CNM, cohesin, lampbrush chromosome Abstract Using immunostaining with antibodies against cohesin subunits, we show here that cohesin-enriched structures analogous to the so-called centromere protein bodies (PB) are the characteristic of galliform lampbrush chromosomes. Their centromeric location was verified by FISH with certain DNA probes. PB-like structures were used as markers for centromere localization in chicken lampbrush chromosomes. The gap predicted to be centromeric in current chicken chromosome 3 sequence assembly was found to correspond to the non- centromeric cluster of CNM repeat on the q-arm of chromosome 3; the centromere is proposed to be placed at another position. The majority of chicken microchromosomes were found to be acrocentric, in contrast to Japanese quail microchromosomes which are biarmed. Centromere cohesin-enriched structures on chicken and quail lampbrush microchromosomes co-localize with pericentromeric CNM and BglIIj repeats respectively. FISH to the nascent transcripts on chicken lampbrush chromosomes revealed numerous non-centromeric CNM clusters in addition to pericentromeric arrays. Complementary CNM transcripts from both C- and G-rich DNA strands were revealed during the lampbrush stage.