Histone H3.3 and Its Proteolytically Processed Form Drive a Cellular Senescence Programme
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Funktionelle in Vitro Und in Vivo Charakterisierung Des Putativen Tumorsuppressorgens SFRP1 Im Humanen Mammakarzinom
Funktionelle in vitro und in vivo Charakterisierung des putativen Tumorsuppressorgens SFRP1 im humanen Mammakarzinom Von der Fakult¨at fur¨ Mathematik, Informatik und Naturwissenschaften der RWTH Aachen University zur Erlangung des akademischen Grades einer Doktorin der Naturwissenschaften genehmigte Dissertation vorgelegt von Diplom-Biologin Laura Huth (geb. Franken) aus Julich¨ Berichter: Universit¨atsprofessor Dr. rer. nat. Edgar Dahl Universit¨atsprofessor Dr. rer. nat. Ralph Panstruga Tag der mundlichen¨ Prufung:¨ 6. August 2014 Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfugbar.¨ Zusammenfassung Krebserkrankungen stellen weltweit eine der h¨aufigsten Todesursachen dar. Aus diesem Grund ist die Aufkl¨arung der zugrunde liegenden Mechanismen und Ur- sachen ein essentielles Ziel der molekularen Onkologie. Die Tumorforschung der letzten Jahre hat gezeigt, dass die Entstehung solider Karzinome ein Mehrstufen- Prozess ist, bei dem neben Onkogenen auch Tumorsuppresorgene eine entschei- dende Rolle spielen. Viele der heute bekannten Gene des WNT-Signalweges wur- den bereits als Onkogene oder Tumorsuppressorgene charakterisiert. Eine Dere- gulation des WNT-Signalweges wird daher mit der Entstehung und Progression vieler humaner Tumorentit¨aten wie beispielsweise auch dem Mammakarzinom, der weltweit h¨aufigsten Krebserkrankung der Frau, assoziiert. SFRP1, ein nega- tiver Regulator der WNT-Signalkaskade, wird in Brusttumoren haupts¨achlich durch den epigenetischen Mechanismus der Promotorhypermethylierung -
Regulation of Oxidized Base Damage Repair by Chromatin Assembly Factor 1 Subunit a Chunying Yang1,*,†, Shiladitya Sengupta1,2,*,†, Pavana M
Published online 27 October 2016 Nucleic Acids Research, 2017, Vol. 45, No. 2 739–748 doi: 10.1093/nar/gkw1024 Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A Chunying Yang1,*,†, Shiladitya Sengupta1,2,*,†, Pavana M. Hegde1,JoyMitra1, Shuai Jiang3, Brooke Holey3, Altaf H. Sarker3, Miaw-Sheue Tsai3, Muralidhar L. Hegde1,2,4 and Sankar Mitra1,2,* 1Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA, 2Weill Cornell Medical College, Cornell University, New York, NY 10065, USA, 3Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA and 4Houston Methodist Neurological Institute, Houston, TX 77030, USA Received March 23, 2016; Revised October 13, 2016; Editorial Decision October 17, 2016; Accepted October 19, 2016 ABSTRACT INTRODUCTION Reactive oxygen species (ROS), generated both en- ROS, continuously generated in mammalian cells both en- dogenously and in response to exogenous stress, in- dogenously and by environmental genotoxicants, induce duce point mutations by mis-replication of oxidized various genomic lesions, including oxidized bases, abasic bases and other lesions in the genome. Repair of (AP) sites and single-strand breaks (SSBs). If unrepaired or these lesions via base excision repair (BER) pathway mis-repaired, DNA lesions would cause mutations which may lead to cytotoxicity and cell death and also carcino- maintains genomic fidelity. Regulation of the BER genic transformation (1). The base excision repair (BER) pathway for mutagenic oxidized bases, initiated by pathway, responsible for repair of oxidized base lesions NEIL1 and other DNA glycosylases at the chromatin which contribute to drug/radiation sensitivity is highly con- level remains unexplored. -
Understanding Chronic Kidney Disease: Genetic and Epigenetic Approaches
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Understanding Chronic Kidney Disease: Genetic And Epigenetic Approaches Yi-An Ko Ko University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, Genetics Commons, and the Systems Biology Commons Recommended Citation Ko, Yi-An Ko, "Understanding Chronic Kidney Disease: Genetic And Epigenetic Approaches" (2017). Publicly Accessible Penn Dissertations. 2404. https://repository.upenn.edu/edissertations/2404 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2404 For more information, please contact [email protected]. Understanding Chronic Kidney Disease: Genetic And Epigenetic Approaches Abstract The work described in this dissertation aimed to better understand the genetic and epigenetic factors influencing chronic kidney disease (CKD) development. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) significantly associated with chronic kidney disease. However, these studies have not effectively identified target genes for the CKD variants. Most of the identified variants are localized to non-coding genomic regions, and how they associate with CKD development is not well-understood. As GWAS studies only explain a small fraction of heritability, we hypothesized that epigenetic changes could explain part of this missing heritability. To identify potential gene targets of the genetic variants, we performed expression quantitative loci (eQTL) analysis, using genotyping arrays and RNA sequencing from human kidney samples. To identify the target genes of CKD-associated SNPs, we integrated the GWAS-identified SNPs with the eQTL results using a Bayesian colocalization method, coloc. This resulted in a short list of target genes, including PGAP3 and CASP9, two genes that have been shown to present with kidney phenotypes in knockout mice. -
Myopia in African Americans Is Significantly Linked to Chromosome 7P15.2-14.2
Genetics Myopia in African Americans Is Significantly Linked to Chromosome 7p15.2-14.2 Claire L. Simpson,1,2,* Anthony M. Musolf,2,* Roberto Y. Cordero,1 Jennifer B. Cordero,1 Laura Portas,2 Federico Murgia,2 Deyana D. Lewis,2 Candace D. Middlebrooks,2 Elise B. Ciner,3 Joan E. Bailey-Wilson,1,† and Dwight Stambolian4,† 1Department of Genetics, Genomics and Informatics and Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States 2Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States 3The Pennsylvania College of Optometry at Salus University, Elkins Park, Pennsylvania, United States 4Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States Correspondence: Joan E. PURPOSE. The purpose of this study was to perform genetic linkage analysis and associ- Bailey-Wilson, NIH/NHGRI, 333 ation analysis on exome genotyping from highly aggregated African American families Cassell Drive, Suite 1200, Baltimore, with nonpathogenic myopia. African Americans are a particularly understudied popula- MD 21131, USA; tion with respect to myopia. [email protected]. METHODS. One hundred six African American families from the Philadelphia area with a CLS and AMM contributed equally to family history of myopia were genotyped using an Illumina ExomePlus array and merged this work and should be considered co-first authors. with previous microsatellite data. Myopia was initially measured in mean spherical equiv- JEB-W and DS contributed equally alent (MSE) and converted to a binary phenotype where individuals were identified as to this work and should be affected, unaffected, or unknown. -
Differential Requirements for Tousled-Like Kinases 1 and 2 in Mammalian Development
Cell Death and Differentiation (2017) 24, 1872–1885 & 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1350-9047/17 www.nature.com/cdd Differential requirements for Tousled-like kinases 1 and 2 in mammalian development Sandra Segura-Bayona1,8, Philip A Knobel1,8, Helena González-Burón1,8, Sameh A Youssef2,3, Aida Peña-Blanco1, Étienne Coyaud4,5, Teresa López-Rovira1, Katrin Rein1, Lluís Palenzuela1, Julien Colombelli1, Stephen Forrow1, Brian Raught4,5, Anja Groth6, Alain de Bruin2,7 and Travis H Stracker*,1 The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance. -
Cross-Talk Between Histone H3 Tails Produces Cooperative Nucleosome Acetylation
Cross-talk between histone H3 tails produces cooperative nucleosome acetylation Shanshan Li and Michael A. Shogren-Knaak1 Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011 Edited by Jerry L. Workman, Stowers Institute for Medical Research, Kansas City, MO, and accepted by the Editorial Board September 23, 2008 (received for review May 9, 2008) Acetylation of histone proteins by the yeast Spt-Ada-Gcn5-acetyl- nucleosomes, with an average distance between nucleosome cen- tansferase (SAGA) complex has served as a paradigm for under- ters of 212 bp (12). Although these nucleosomes are arrayed in a standing how posttranslational modifications of chromatin regu- linear fashion in genomic sequence, in many cases they adopt more late eukaryotic gene expression. Nonetheless, it has been unclear complex higher-order structures. Short-range interactions between to what extent the structural complexity of the chromatin sub- nucleosomes within a strand of chromatin allow chromatin to adopt strate modulates SAGA activity. By using chromatin model sys- a more compact 30-nm fiber structure (13, 14), and long-range tems, we have found that SAGA-mediated histone acetylation is interactions between distant nucleosomes provide a means for .(highly cooperative (cooperativity constant of 1.97 ؎ 0.15), employ- chromatin to potentially adopt 100- to 400-nm fiber structures (15 ing the binding of multiple noncontiguous nucleosomes to facili- Moreover, a number of recent studies suggest that different func- tate maximal acetylation activity. Studies with various chromatin tional forms of chromatin can adopt complex looping structures, substrates, including those containing novel asymmetric histone where regions of the genome that are separated by large distances octamers, indicate that this cooperativity occurs only when both in sequence can be brought together in space (16). -
TLK2 Antibody (Center) Purified Rabbit Polyclonal Antibody (Pab) Catalog # Ap8102c
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 TLK2 Antibody (Center) Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP8102c Specification TLK2 Antibody (Center) - Product Information Application WB,E Primary Accession Q86UE8 Other Accession Q9UKI7 Reactivity Human, Mouse Host Rabbit Clonality Polyclonal Isotype Rabbit Ig Antigen Region 141-171 TLK2 Antibody (Center) - Additional Information Western blot analysis of anti-TLK2 Antibody Gene ID 11011 (Center) (Cat.#AP8102c) in mouse testis tissue lysates (35ug/lane).TLK2(arrow) was Other Names detected using the purified Pab. Serine/threonine-protein kinase tousled-like 2, HsHPK, PKU-alpha, Tousled-like kinase 2, TLK2 Target/Specificity This TLK2 antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 141-171 amino acids from the Central region of human TLK2. Dilution WB~~1:1000 Format Purified polyclonal antibody supplied in PBS TLK2 Antibody (K155) (Cat. #AP8102c) with 0.09% (W/V) sodium azide. This western blot analysis in Y79 cell line lysates antibody is prepared by Saturated (35ug/lane).This demonstrates the TLK2 Ammonium Sulfate (SAS) precipitation antibody detected the TLK2 protein (arrow). followed by dialysis against PBS. Storage TLK2 Antibody (Center) - Background Maintain refrigerated at 2-8°C for up to 2 weeks. For long term storage store at -20°C in small aliquots to prevent freeze-thaw TLK2, a member of the Ser/Thr protein kinase cycles. family, is rapidly and transiently inhibited by phosphorylation following the generation of Precautions DNA double-stranded breaks during S-phase. TLK2 Antibody (Center) is for research use This is cell cycle checkpoint and ATM-pathway only and not for use in diagnostic or dependent and appears to regulate processes therapeutic procedures. -
Histones H3 and H4 Are Components of Upstream Activation Factor Required for the High-Level Transcription of Yeast Rdna by RNA Polymerase I
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 13458–13462, December 1997 Biochemistry Histones H3 and H4 are components of upstream activation factor required for the high-level transcription of yeast rDNA by RNA polymerase I JOHN KEENER*, JONATHAN A. DODD*, DOMINIQUE LALO, AND MASAYASU NOMURA† Department of Biological Chemistry, University of California, Irvine, CA 92697-1700 Contributed by Masayasu Nomura, October 16, 1997 ABSTRACT RNA polymerase I (Pol I) transcription in consisting of Rrn6p, Rrn7p, and Rrn11p; refs. 3, 9, and 10), the yeast Saccharomyces cerevisiae is greatly stimulated in vivo Rrn3p (5), and Pol I are required. In addition to these factors, and in vitro by the multiprotein complex, upstream activation upstream activation factor (UAF) and TATA box-binding factor (UAF). UAF binds tightly to the upstream element of the protein, as well as the upstream element, are required for a rDNA promoter, such that once bound (in vitro), UAF does not high level of transcription from the yeast rDNA promoter (4, readily exchange onto a competing template. Of the polypep- 11). Purified UAF previously was shown to contain three tides previously identified in purified UAF, three are encoded genetically defined subunits, Rrn5p, Rrn9p, and Rrn10p, and by genes required for Pol I transcription in vivo: RRN5, RRN9, two uncharacterized subunits, p30 and p18 (4). and RRN10. Two others, p30 and p18, have remained unchar- DNA in the eukaryotic nucleus is organized as chromatin, acterized. We report here that the N-terminal amino acid consisting mostly of regularly repeating nucleosomes in which sequence, its mobility in gel electrophoresis, and the immu- DNA is wrapped around an octameric structure of core noreactivity of p18 shows that it is histone H3. -
Induce Latent/Quiescent HSV-1 Genomes
Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis Camille Cohen, Armelle Corpet, Simon Roubille, Mohamed Maroui, Nolwenn Poccardi, Antoine Rousseau, Constance Kleijwegt, Olivier Binda, Pascale Texier, Nancy Sawtell, et al. To cite this version: Camille Cohen, Armelle Corpet, Simon Roubille, Mohamed Maroui, Nolwenn Poccardi, et al.. Promye- locytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 genomes chromatiniza- tion through a PML NB/Histone H3.3/H3.3 Chaperone Axis. PLoS Pathogens, Public Library of Science, 2018, 14 (9), pp.e1007313. 10.1371/journal.ppat.1007313. inserm-02167220 HAL Id: inserm-02167220 https://www.hal.inserm.fr/inserm-02167220 Submitted on 27 Jun 2019 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. RESEARCH ARTICLE Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis Camille Cohen1, Armelle Corpet1, Simon -
Structure–Function Studies of Histone H3/H4 Tetramer Maintenance During Transcription by Chaperone Spt2
Downloaded from genesdev.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Structure–function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2 Shoudeng Chen,1,5 Anne Rufiange,2,5 Hongda Huang,1 Kanagalaghatta R. Rajashankar,3,4 Amine Nourani,2 and Dinshaw J. Patel1 1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA; 2Groupe St-Patrick de Recherche en Oncologie Fondamentale, L’Hôtel-Dieu de Québec (Université Laval), Québec G1R 2J6, Canada; 3Northeastern Collaborative Access Team (NE-CAT), Advanced Photon Source, Argonne National Laboratory, Chicago, Illinois 60439, USA; 4Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA Cells use specific mechanisms such as histone chaperones to abrogate the inherent barrier that the nucleosome poses to transcribing polymerases. The current model postulates that nucleosomes can be transiently disrupted to accommodate passage of RNA polymerases and that histones H3 and H4 possess their own chaperones dedicated to the recovery of nucleosomes. Here, we determined the crystal structure of the conserved C terminus of human Suppressors of Ty insertions 2 (hSpt2C) chaperone bound to an H3/H4 tetramer. The structural studies demonstrate that hSpt2C is bound to the periphery of the H3/H4 tetramer, mimicking the trajectory of nucleosomal-bound DNA. These structural studies have been complemented with in vitro binding and in vivo functional studies on mutants that disrupt key intermolecular contacts involving two acidic patches and hydrophobic residues on Spt2C. We show that contacts between both human and yeast Spt2C with the H3/H4 tetramer are required for the suppression of H3/ H4 exchange as measured by H3K56ac and new H3 deposition. -
The Histone Variant H3.3 Marks Active Chromatin by Replication-Independent Nucleosome Assembly
Molecular Cell, Vol. 9, 1191–1200, June, 2002, Copyright 2002 by Cell Press The Histone Variant H3.3 Marks Active Chromatin by Replication-Independent Nucleosome Assembly Kami Ahmad and Steven Henikoff1 ment are not clear. A study in Tetrahymena concluded Fred Hutchinson Cancer Research Center that no protein difference between histone H3 variants 1100 Fairview Avenue North was required for replacement histone deposition and Seattle, Washington 98109 that expression of either variant outside of S phase ap- peared to be sufficient (Yu and Gorovsky, 1997). In con- trast, by examining the dynamics of histone proteins in Summary Drosophila nuclei we show that the major histone H3 and the replacement histone H3.3 proteins have distinct Two very similar H3 histones—differing at only four properties during in vivo chromatin assembly. Histone amino acid positions—are produced in Drosophila H3.3 participates in replication-independent (RI) nucleo- cells. Here we describe a mechanism of chromatin some assembly and is targeted to transcriptionally ac- regulation whereby the variant H3.3 is deposited at tive loci throughout the cell cycle. Transcription-coupled particular loci, including active rDNA arrays. While the deposition of H3.3-containing nucleosomes may be a major H3 is incorporated strictly during DNA replica- general mechanism for rapidly replacing permanently tion, amino acid changes toward H3.3 allow replica- modified nucleosomes and for heritably activating tion-independent (RI) deposition. In contrast to repli- genes. cation-coupled (RC) deposition, RI deposition does not require the N-terminal tail. H3.3 is the exclusive Results substrate for RI deposition, and its counterpart is the only substrate retained in yeast. -
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Produktinformation Diagnostik & molekulare Diagnostik Laborgeräte & Service Zellkultur & Verbrauchsmaterial Forschungsprodukte & Biochemikalien Weitere Information auf den folgenden Seiten! See the following pages for more information! Lieferung & Zahlungsart Lieferung: frei Haus Bestellung auf Rechnung SZABO-SCANDIC Lieferung: € 10,- HandelsgmbH & Co KG Erstbestellung Vorauskassa Quellenstraße 110, A-1100 Wien T. +43(0)1 489 3961-0 Zuschläge F. +43(0)1 489 3961-7 [email protected] • Mindermengenzuschlag www.szabo-scandic.com • Trockeneiszuschlag • Gefahrgutzuschlag linkedin.com/company/szaboscandic • Expressversand facebook.com/szaboscandic CSTL1 Antibody Product Code CSB-PA006101GA01HU Abbreviation CSTL1-Specific Storage Upon receipt, store at -20°C or -80°C. Avoid repeated freeze. Uniprot No. Q9H114 Immunogen Human CSTL1-Specific Raised In Rabbit Species Reactivity Human,Mouse Tested Applications ELISA,IHC Storage Buffer PBS with 0.02% Sodium Azide, 50% Glycerol, pH 7.3. -20°C, Avoid freeze / thaw cycles. Purification Method Antigen Affinity purified Isotype IgG Alias cystatin-like 1;CSTL1;RCET11;dJ322G13.4 ; Product Type Purified Rabbit Anti Human PolyClonal Antibody Species Homo sapiens (Human) Target Names CSTL1 Target Details The cystatin superfamily encompasses proteins that contain multiple cystatin- like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located at the telomeric end of the cystatin locus and encodes a type 2 cystatin-like protein.