Supplementary Material Localizing Regions in the Genome
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Constitutive Scaffolding of Multiple Wnt Enhanceosome Components By
RESEARCH ARTICLE Constitutive scaffolding of multiple Wnt enhanceosome components by Legless/ BCL9 Laurens M van Tienen, Juliusz Mieszczanek, Marc Fiedler, Trevor J Rutherford, Mariann Bienz* MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Abstract Wnt/b-catenin signaling elicits context-dependent transcription switches that determine normal development and oncogenesis. These are mediated by the Wnt enhanceosome, a multiprotein complex binding to the Pygo chromatin reader and acting through TCF/LEF- responsive enhancers. Pygo renders this complex Wnt-responsive, by capturing b-catenin via the Legless/BCL9 adaptor. We used CRISPR/Cas9 genome engineering of Drosophila legless (lgs) and human BCL9 and B9L to show that the C-terminus downstream of their adaptor elements is crucial for Wnt responses. BioID proximity labeling revealed that BCL9 and B9L, like PYGO2, are constitutive components of the Wnt enhanceosome. Wnt-dependent docking of b-catenin to the enhanceosome apparently causes a rearrangement that apposes the BCL9/B9L C-terminus to TCF. This C-terminus binds to the Groucho/TLE co-repressor, and also to the Chip/LDB1-SSDP enhanceosome core complex via an evolutionary conserved element. An unexpected link between BCL9/B9L, PYGO2 and nuclear co-receptor complexes suggests that these b-catenin co-factors may coordinate Wnt and nuclear hormone responses. DOI: 10.7554/eLife.20882.001 *For correspondence: mb2@mrc- Introduction lmb.cam.ac.uk The Wnt/b-catenin signaling cascade is an ancient cell communication pathway that operates con- Competing interests: The text-dependent transcriptional switches to control animal development and tissue homeostasis authors declare that no (Cadigan and Nusse, 1997). -
Investigation of Functional Genes at Homologous Loci Identified Based
Journal of Atherosclerosis and Thrombosis Vol.22, No.5 455 Original Article Investigation of Functional Genes at Homologous Loci Identified Based on Genome-wide Association Studies of Blood Lipids via High-fat Diet Intervention in Rats using an in vivo Approach Koichi Akiyama, Yi-Qiang Liang, Masato Isono and Norihiro Kato Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan Aim: It is challenging to identify causal (or target) genes at individual loci detected using genome- wide association studies (GWAS). In order to follow up GWAS loci, we investigated functional genes at homologous loci identified using human lipid GWAS that responded to a high-fat, high-choles- terol diet (HFD) intervention in an animal model. Methods: The HFD intervention was carried out for four weeks in male rats of the spontaneously hypertensive rat strain. The liver and adipose tissues were subsequently excised for analyses of changes in the gene expression as compared to that observed in rats fed normal rat chow (n=8 per group). From 98 lipid-associated loci reported in previous GWAS, 280 genes with rat orthologs were initially selected as targets for the two-staged analysis involving screening with DNA microarray and validation with quantitative PCR (qPCR). Consequently, genes showing a differential expression due to HFD were examined for changes in the expression induced by atorvastatin, which was indepen- dently administered to the rats. Results: Using the HFD intervention in the rats, seven known (Abca1, Abcg5, Abcg8, Lpl, Nr1h3, Pcsk9 and Pltp) and three novel (Madd, Stac3 and Timd4) genes were identified as potential signifi- cant targets, with an additional list of 23 suggestive genes. -
The Role of Methionine Sulfoxide Reductases in Oxidative Stress Tolerance and Virulence of Staphylococcus Aureus and Other Bacteria
antioxidants Review The Role of Methionine Sulfoxide Reductases in Oxidative Stress Tolerance and Virulence of Staphylococcus aureus and Other Bacteria Vineet K. Singh 1,* , Kuldeep Singh 2 and Kyle Baum 1 1 Department of Microbiology and Immunology, A.T. Still University of Health Sciences, Kirksville, MO 63501, USA; [email protected] 2 Mayo Clinic, Rochester, MN 53905, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-660-626-2474; Fax: +1-660-626-2523 Received: 31 August 2018; Accepted: 26 September 2018; Published: 28 September 2018 Abstract: Methionine sulfoxide reductases (MSRA1 and MSRB) are proteins overproduced in Staphylococcus aureus during exposure with cell wall-active antibiotics. Later studies identified the presence of two additional MSRA proteins (MSRA2 and MSRA3) in S. aureus. These MSR proteins have been characterized in many other bacteria as well. This review provides the current knowledge about the conditions and regulatory network that mimic the expression of these MSR encoding genes and their role in defense from oxidative stress and virulence. Keywords: MSRA; MSRB; oxidative stress; virulence 1. Methionine Sulfoxide Reductases The presence of reactive oxygen species (ROS) is potentially damaging to all cellular macromolecules. Oxidizing agents, such as hydrogen peroxide (H2O2), superoxides, and hydroxyl radicals, oxidize the sulfur atom of methionine residues, resulting in methionine sulfoxide (MetO) that typically leads to loss of protein function [1,2]. In 1981, an enzyme capable of reducing protein-bound methionine sulfoxide was identified [3,4]. These oxidized MetO residues are reduced back to methionine by methionine sulfoxide reductase (MSR) enzymes that restore normal protein functions [5,6]. -
Distribution of Methionine Sulfoxide Reductases in Fungi and Conservation of the Free- 2 Methionine-R-Sulfoxide Reductase in Multicellular Eukaryotes
bioRxiv preprint doi: https://doi.org/10.1101/2021.02.26.433065; this version posted February 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Distribution of methionine sulfoxide reductases in fungi and conservation of the free- 2 methionine-R-sulfoxide reductase in multicellular eukaryotes 3 4 Hayat Hage1, Marie-Noëlle Rosso1, Lionel Tarrago1,* 5 6 From: 1Biodiversité et Biotechnologie Fongiques, UMR1163, INRAE, Aix Marseille Université, 7 Marseille, France. 8 *Correspondence: Lionel Tarrago ([email protected]) 9 10 Running title: Methionine sulfoxide reductases in fungi 11 12 Keywords: fungi, genome, horizontal gene transfer, methionine sulfoxide, methionine sulfoxide 13 reductase, protein oxidation, thiol oxidoreductase. 14 15 Highlights: 16 • Free and protein-bound methionine can be oxidized into methionine sulfoxide (MetO). 17 • Methionine sulfoxide reductases (Msr) reduce MetO in most organisms. 18 • Sequence characterization and phylogenomics revealed strong conservation of Msr in fungi. 19 • fRMsr is widely conserved in unicellular and multicellular fungi. 20 • Some msr genes were acquired from bacteria via horizontal gene transfers. 21 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.02.26.433065; this version posted February 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
Harnessing Gene Expression Profiles for the Identification of Ex Vivo Drug
cancers Article Harnessing Gene Expression Profiles for the Identification of Ex Vivo Drug Response Genes in Pediatric Acute Myeloid Leukemia David G.J. Cucchi 1 , Costa Bachas 1 , Marry M. van den Heuvel-Eibrink 2,3, Susan T.C.J.M. Arentsen-Peters 3, Zinia J. Kwidama 1, Gerrit J. Schuurhuis 1, Yehuda G. Assaraf 4, Valérie de Haas 3 , Gertjan J.L. Kaspers 3,5 and Jacqueline Cloos 1,* 1 Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; [email protected] (D.G.J.C.); [email protected] (C.B.); [email protected] (Z.J.K.); [email protected] (G.J.S.) 2 Department of Pediatric Oncology/Hematology, Erasmus MC–Sophia Children’s Hospital, 3015 CN Rotterdam, The Netherlands; [email protected] 3 Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; [email protected] (S.T.C.J.M.A.-P.); [email protected] (V.d.H.); [email protected] (G.J.L.K.) 4 The Fred Wyszkowski Cancer Research, Laboratory, Department of Biology, Technion-Israel Institute of Technology, 3200003 Haifa, Israel; [email protected] 5 Emma’s Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The Netherlands * Correspondence: [email protected] Received: 21 April 2020; Accepted: 12 May 2020; Published: 15 May 2020 Abstract: Novel treatment strategies are of paramount importance to improve clinical outcomes in pediatric AML. Since chemotherapy is likely to remain the cornerstone of curative treatment of AML, insights in the molecular mechanisms that determine its cytotoxic effects could aid further treatment optimization. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Specification in Embryonic Stem Cells Through Activation and Repression
Article Polycomb Regulates Mesoderm Cell Fate- Specification in Embryonic Stem Cells through Activation and Repression Mechanisms Graphical Abstract Authors Lluis Morey, Alexandra Santanach, Enrique Blanco, ..., Elphe` ge P. Nora, Benoit G. Bruneau, Luciano Di Croce Correspondence [email protected] (L.M.), [email protected] (L.D.C.) In Brief Morey et al. reveal that Mel18, a Polycomb-complex-associated protein, is an essential epigenetic regulator of cardiac differentiation. During directed differentiation of embryonic stem cells, Morey et al. find that Mel18-PRC1 complexes exchange subunits in a stage- specific manner and instruct sequential gene activation and repression programs to specify mesoderm fate, prevent alternate lineage commitment, and promote cardiac differentiation. Highlights Accession Numbers d Mel18 is required for PRC1 stability and maintenance of gene GSE67868 repression in ESCs d Mel18 is essential for ESC differentiation into early cardiac- mesoderm precursors d Different Mel18-PRC1 complexes are assembled during cardiac differentiation d Distinctive PRC1 complexes bind to highly active and repressed genes in MES cells Morey et al., 2015, Cell Stem Cell 17, 300–315 September 3, 2015 ª2015 Elsevier Inc. http://dx.doi.org/10.1016/j.stem.2015.08.009 Cell Stem Cell Article Polycomb Regulates Mesoderm Cell Fate-Specification in Embryonic Stem Cells through Activation and Repression Mechanisms Lluis Morey,1,2,6,* Alexandra Santanach,1,2 Enrique Blanco,1,2 Luigi Aloia,1,2 Elphe` ge P. Nora,3,4 Benoit G. Bruneau,3,4 -
Microrna Expression Signature of Oral Squamous Cell Carcinoma: Functional Role of Microrna-26A&Sol;B in the Modulation of No
FULL PAPER British Journal of Cancer (2015) 112, 891–900 | doi: 10.1038/bjc.2015.19 Keywords: microRNA; oral squamous cell carcinoma; miR-26a; miR-26b; tumour suppressor; TMEM184B; expression signature MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways I Fukumoto1,2, T Hanazawa2, T Kinoshita1,2, N Kikkawa2, K Koshizuka1,2, Y Goto1, R Nishikawa1, T Chiyomaru3, H Enokida3, M Nakagawa3, Y Okamoto2 and N Seki*,1 1Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan; 2Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan and 3Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Background: MicroRNAs (miRNAs) have been shown to play major roles in carcinogenesis in a variety of cancers. The aim of this study was to determine the miRNA expression signature of oral squamous cell carcinoma (OSCC) and to investigate the functional roles of miR-26a and miR-26b in OSCC cells. Methods: An OSCC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were performed to investigate cell proliferation, migration, and invasion in OSCC cells. In silico database and genome-wide gene expression analyses were performed to identify molecular targets and pathways mediated by miR-26a/b. Results: miR-26a and miR-26b were significantly downregulated in OSCC. Restoration of both miR-26a and miR-26b in cancer cell lines revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our data demonstrated that the novel transmembrane TMEM184B gene was a direct target of miR-26a/b regulation. -
Genetic and Genomic Analysis of Hyperlipidemia, Obesity and Diabetes Using (C57BL/6J × TALLYHO/Jngj) F2 Mice
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Nutrition Publications and Other Works Nutrition 12-19-2010 Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P. Stewart Marshall University Hyoung Y. Kim University of Tennessee - Knoxville, [email protected] Arnold M. Saxton University of Tennessee - Knoxville, [email protected] Jung H. Kim Marshall University Follow this and additional works at: https://trace.tennessee.edu/utk_nutrpubs Part of the Animal Sciences Commons, and the Nutrition Commons Recommended Citation BMC Genomics 2010, 11:713 doi:10.1186/1471-2164-11-713 This Article is brought to you for free and open access by the Nutrition at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Nutrition Publications and Other Works by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. Stewart et al. BMC Genomics 2010, 11:713 http://www.biomedcentral.com/1471-2164/11/713 RESEARCH ARTICLE Open Access Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P Stewart1, Hyoung Yon Kim2, Arnold M Saxton3, Jung Han Kim1* Abstract Background: Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/ JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. -
Large Scale Organization of Chromatin
LARGE SCALE ORGANIZATION OF CHROMATIN MARIO Nicodemi Dip.to di Fisica, Uni.NA “Federico II”, INFN In the cell nucleus chromosomes have a complex architecture serving vital functional purposes. Problem: how is their 3D structure orchestrated? Our contribution: a model of the molecular mechanisms of their self- organization by use of classical polymer physics. (Mirò, Chiffres & Constellations 1941) Research collaborators MRC, Imperial College, London Ana Pombo,, Mita Chotalia, Ines de Santiago, Liron-Mark Lavitas, Sheila Xie, Kedar Natarajan, Carmelo Ferrai, Robert Beagrie, ... Biology, McGill, CA Josée Dostie, James Fraser Physics, Univ. di Napoli, Italy Mariano Barbieri, Ilaria Cataudella, Antonio Scialdone, Melania Barile, Paolo Casale, Valentino Bianco, Emanuela de Falco, Deborah Pallotti, Gaetano Pellegrino, Andrea Piccolo, ... Chromatin organization (I) (A) Linear expression units in compact genomes v.s. spatially assembled units in complex genomes. (B) Colocalization of coregulated genes. (C) ChromatinGene localization organizationat transcription factories (TFs). Example: the Xicʼs of the X Chromosome territories and map chrom.s colocalize at XCI (Heard et al.; Lee et al. ʻ07) Chromatin organizationNuclear scale (I) (A) Linear expression units in compact genomes v.s. spatially assembled units in complex genomes. (B) Colocalization of coregulated genes. (C) Gene localization at transcription factories (TFs). Colocalization of coregulated genes at transcription factories Example: the Xicʼs of the X Transcription chrom.s colocalize at XCI Factory (Heard et al.; Lee et al. ʻ07) (Pictures: Dekker et al. Science ʻ08) Distal regulatory elements Gene Gene Expression Units Assembly of expression units Gene scale (Pictures: Bolzer et al. PLoS Bio. ʼ05; Dekker et al. Science ʼ08) (Pictures: Dekker et al. -
Chromosomal Localization of the Mammalian Peptide-Methionine Sulfoxide Reductase Gene and Its Differential Expression in Various Tissues JACKOB MOSKOVITZ*, NANCY A
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 3205-3208, April 1996 Biochemistry Chromosomal localization of the mammalian peptide-methionine sulfoxide reductase gene and its differential expression in various tissues JACKOB MOSKOVITZ*, NANCY A. JENKINSt, DEBRA J. GILBERTt, NEAL G. COPELANDt, FRANTISEK JURSKY*, HERBERT WEISSBACH*, AND NATHAN BROT* *Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110-1199; and tAdvanced BioScience Laboratory-Basic Research Program, Frederick Cancer Research and Development Center, P.O. Box B, Frederick, MD 21702-1201 Contributed by Herbert Weissbach, December 26, 1996 ABSTRACT Peptide methionine sulfoxide reductase agarose gel electrophoresis, Southern blot transfer, and hy- (MsrA; EC 1.8.4.6) is a ubiquitous protein that can reduce bridization were performed as described (11). All blots were methionine sulfoxide residues in proteins as well as in a large prepared using Hybond-N+ nylon membrane (Amersham). number of methyl sulfoxide compounds. The expression of The probe, a 228-bp PCR-generated mouse cDNA fragment MsrA in various rat tissues was determined by using immu- (6), was labeled with [a-32P]dCTP by random priming (Strat- nocytochemical staining. Although the protein was found in agene), and the blots were washed at 65°C in a buffer con- all tissues examined, it was specifically localized to renal taining 0.8x SSCP and 0.1% SDS (lx SSCP = 120 mM medulla and retinal pigmented epithelial cells, and it was NaCl/15 mM sodium citrate/20 mM sodium phosphate, pH prominent in neurons and throughout the nervous system. In 6.8). A 5.8-kb fragment was detected in Sph I-digested addition, blood and alveolar macrophages showed high ex- C57BL/6J (B) genomic DNA and an 8.2-kb fragment, in Sph pression of the enzyme. -
Supplementary Table 1: Adhesion Genes Data Set
Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,