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Genome-Wide Analysis of 5-Hmc in the Peripheral Blood of Systemic Lupus Erythematosus Patients Using an Hmedip-Chip
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 35: 1467-1479, 2015 Genome-wide analysis of 5-hmC in the peripheral blood of systemic lupus erythematosus patients using an hMeDIP-chip WEIGUO SUI1*, QIUPEI TAN1*, MING YANG1, QIANG YAN1, HUA LIN1, MINGLIN OU1, WEN XUE1, JIEJING CHEN1, TONGXIANG ZOU1, HUANYUN JING1, LI GUO1, CUIHUI CAO1, YUFENG SUN1, ZHENZHEN CUI1 and YONG DAI2 1Guangxi Key Laboratory of Metabolic Diseases Research, Central Laboratory of Guilin 181st Hospital, Guilin, Guangxi 541002; 2Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, P.R. China Received July 9, 2014; Accepted February 27, 2015 DOI: 10.3892/ijmm.2015.2149 Abstract. Systemic lupus erythematosus (SLE) is a chronic, Introduction potentially fatal systemic autoimmune disease characterized by the production of autoantibodies against a wide range Systemic lupus erythematosus (SLE) is a typical systemic auto- of self-antigens. To investigate the role of the 5-hmC DNA immune disease, involving diffuse connective tissues (1) and modification with regard to the onset of SLE, we compared is characterized by immune inflammation. SLE has a complex the levels 5-hmC between SLE patients and normal controls. pathogenesis (2), involving genetic, immunologic and envi- Whole blood was obtained from patients, and genomic DNA ronmental factors. Thus, it may result in damage to multiple was extracted. Using the hMeDIP-chip analysis and valida- tissues and organs, especially the kidneys (3). SLE arises from tion by quantitative RT-PCR (RT-qPCR), we identified the a combination of heritable and environmental influences. differentially hydroxymethylated regions that are associated Epigenetics, the study of changes in gene expression with SLE. -
How Shelterin Protects Mammalian Telomeres 303 ANRV361-GE42-15 ARI 3 October 2008 10:10 (See 3' 5' TRF2 S Mplex
ANRV361-GE42-15 ARI 3 October 2008 10:10 ANNUAL How Shelterin Protects REVIEWS Further Click here for quick links to Annual Reviews content online, Mammalian Telomeres including: • Other articles in this volume 1 • Top cited articles Wilhelm Palm and Titia de Lange • Top downloaded articles • Our comprehensive search Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021; email: [email protected] 1Current address: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany Annu. Rev. Genet. 2008. 42:301–34 Key Words First published online as a Review in Advance on ATM, ATR, cancer, NHEJ, HR August 4, 2008 by Rockefeller University on 10/13/09. For personal use only. The Annual Review of Genetics is online at Abstract genet.annualreviews.org The genomes of prokaryotes and eukaryotic organelles are usually cir- This article’s doi: cular as are most plasmids and viral genomes. In contrast, the nuclear Annu. Rev. Genet. 2008.42:301-334. Downloaded from arjournals.annualreviews.org 10.1146/annurev.genet.41.110306.130350 genomes of eukaryotes are organized on linear chromosomes, which Copyright c 2008 by Annual Reviews. require mechanisms to protect and replicate DNA ends. Eukaryotes All rights reserved navigate these problemswith the advent of telomeres, protective nucle- 0066-4197/08/1201-0301$20.00 oprotein complexes at the ends of linear chromosomes, and telomerase, the enzyme that maintains the DNA in these structures. Mammalian telomeres contain a specific protein complex, shelterin, that functions to protect chromosome ends from all aspects of the DNA damage re- sponse and regulates telomere maintenance by telomerase. -
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. -
Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
Chromosomal Rearrangements Are Commonly Post-Transcriptionally Attenuated in Cancer
bioRxiv preprint doi: https://doi.org/10.1101/093369; this version posted February 1, 2017. 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 4.0 International license. Chromosomal rearrangements are commonly post-transcriptionally attenuated in cancer 1 3 1 3, 4, 5 Emanuel Gonçalves , Athanassios Fragoulis , Luz Garcia-Alonso , Thorsten Cramer , 1,2# 1# Julio Saez-Rodriguez , Pedro Beltrao 1 European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK 2 RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine, Aachen 52057, Germany 3 Molecular Tumor Biology, Department of General, Visceral and Transplantation Surgery, RWTH University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany 4 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands 5 ESCAM – European Surgery Center Aachen Maastricht, Germany and The Netherlands # co-last authors: [email protected]; [email protected] Running title: Chromosomal rearrangement attenuation in cancer Keywords: Cancer; Gene dosage; Proteomics; Copy-number variation; Protein complexes 1 bioRxiv preprint doi: https://doi.org/10.1101/093369; this version posted February 1, 2017. 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 4.0 International license. Abstract Chromosomal rearrangements, despite being detrimental, are ubiquitous in cancer and often act as driver events. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Signature of Progression and Negative Outcome in Colorectal Cancer
Oncogene (2010) 29, 876–887 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 $32.00 www.nature.com/onc ORIGINAL ARTICLE A ‘DNA replication’ signature of progression and negative outcome in colorectal cancer M-J Pillaire1,7, J Selves2,7, K Gordien2, P-A Gouraud3, C Gentil3, M Danjoux2,CDo3, V Negre4, A Bieth1, R Guimbaud2, D Trouche5, P Pasero6,MMe´chali6, J-S Hoffmann1 and C Cazaux1 1Genetic Instability and Cancer Group, Department Biology of Cancer, Institute of Pharmacology and Structural Biology, UMR5089 CNRS, University of Toulouse, University Paul Sabatier, Toulouse, France; 2INSERM U563, Federation of Digestive Cancerology and Department of Anatomo-pathology, University of Toulouse, University Paul Sabatier, Toulouse, France; 3Service of Epidemiology, INSERM U558, Faculty of Medicine, University of Toulouse, University Paul Sabatier, Alle´es Jules Guesde, Toulouse, France; 4aCGH GSO Canceropole Platform, INSERM U868, Val d’Aurelle, Montpellier, France; 5Laboratory of Cellular and Molecular Biology of Cell Proliferation Control, UMR 5099 CNRS, University of Toulouse, University Paul Sabatier, Toulouse, France and 6Institute of Human Genetics UPR1142 CNRS, Montpellier, France Colorectal cancer is one of the most frequent cancers Introduction worldwide. As the tumor-node-metastasis (TNM) staging classification does not allow to predict the survival of DNA replication in normal cells is regulated by an patients in many cases, additional prognostic factors are ‘origin licensing’ mechanism that ensures that it occurs needed to better forecast their outcome. Genes involved in just once per cycle. Once cells enter the S-phase, the DNA replication may represent an underexplored source stability of DNA replication forks must be preserved to of such prognostic markers. -
Supplementary Table 2
Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942 -
Crosstalk Between Repair Pathways Elicits Double-Strand Breaks In
RESEARCH ARTICLE Crosstalk between repair pathways elicits double-strand breaks in alkylated DNA and implications for the action of temozolomide Robert P Fuchs1†*, Asako Isogawa2, Joao A Paulo3, Kazumitsu Onizuka4, Tatsuro Takahashi5, Ravindra Amunugama1, Julien P Duxin1‡, Shingo Fujii2 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States; 2Cancer Research Center of Marseille, UMR7258, CNRS, Marseille, France; 3Department of Cell Biology, Harvard Medical School, Boston, United States; 4Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan; 5Faculty of Science, Kyushu University, Fukuoka, Japan Abstract Temozolomide (TMZ), a DNA methylating agent, is the primary chemotherapeutic drug used in glioblastoma treatment. TMZ induces mostly N-alkylation adducts (N7-methylguanine and N3-methyladenine) and some O6-methylguanine (O6mG) adducts. Current models propose that *For correspondence: during DNA replication, thymine is incorporated across from O6mG, promoting a futile cycle of [email protected] mismatch repair (MMR) that leads to DNA double-strand breaks (DSBs). To revisit the mechanism † Present address: Marseille of O6mG processing, we reacted plasmid DNA with N-methyl-N-nitrosourea (MNU), a Medical Genetics, UMR1251, temozolomide mimic, and incubated it in Xenopus egg-derived extracts. We have shown that in this ‡ Marseille, France; The Novo system, MMR proteins are enriched on MNU-treated DNA and we observed robust, MMR- Nordisk Foundation Center for dependent, repair synthesis. Our evidence also suggests that MMR, initiated at O6mG:C sites, is Protein Research, University of strongly stimulated in cis by repair processing of other lesions, such as N-alkylation adducts. Copenhagen, Copenhagen, Denmark Importantly, MNU-treated plasmids display DSBs in extracts, the frequency of which increases linearly with the square of alkylation dose. -
The Licensing Protein Orc4 Is Required for Polar Body Extrusion During Murine Meiosis
THE LICENSING PROTEIN ORC4 IS REQUIRED FOR POLAR BODY EXTRUSION DURING MURINE MEIOSIS A DISSERTATION SUBMITTED TO THE GRADUATE DIVISION OF THE UNIVERSITY OF HAWAIʻI AT MĀNOA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTORAL OF PHILOSOPHY IN DEVELOPMENTAL AND REPRODUCTIVE BIOLOGY DECEMBER 2017 By Hieu Thi Nguyen Dissertation Committee: David M. Jameson, Ph.D., University Representative W. Steven Ward, Ph.D., Chairperson Monika Ward, Ph.D. Yusuke Marikawa, Ph.D. Yukiko Yamazaki, Ph.D. Keywords: DNA replication, chromosomes, embryo development, ORC4, Polar body extrusion DEDICATION I dedicate this dissertation to my mom (My Thu), my dad (Nguyen Van Ngu), Tu, Lam, Gieng, Thao, Van, Hanh and to the rest of the members of the Nguyen family past and future, and especially to my husband (Nick James) whom provided me with guidance through the hardest times of graduate school. ii ACKNOWLEDGEMENTS I would firstly like to express my sincere gratitude to my advisor Dr. W. Steven Ward who has provided strong support of my dissertation and helped me through this process with patience, intellectual support, motivating me to take questions further, and his caring nature. There was never a time that I could not ask Dr. Ward for his assistance, whether for research or life questions, and for that I will forever be grateful. I could not image having a better advisor for my Ph.D. research. I would also like to thank my dissertation committee: Dr. Monika Ward, Dr. Yusuke Marikawa, Dr. Yukiko Yamazaki, and Dr. David Jameson for their time, effort, insightful comments, and encouragement during my Ph.D. -
Drosophila Melanogaster Marat Sabirov1,2†, Olga Kyrchanova1,2†, Galina V
Sabirov et al. Epigenetics & Chromatin (2021) 14:16 https://doi.org/10.1186/s13072-021-00391-x Epigenetics & Chromatin RESEARCH Open Access Mechanism and functional role of the interaction between CP190 and the architectural protein Pita in Drosophila melanogaster Marat Sabirov1,2†, Olga Kyrchanova1,2†, Galina V. Pokholkova3†, Artem Bonchuk1,2†, Natalia Klimenko2, Elena Belova1,2, Igor F. Zhimulev3, Oksana Maksimenko2* and Pavel Georgiev1* Abstract Background: Pita is required for Drosophila development and binds specifcally to a long motif in active promoters and insulators. Pita belongs to the Drosophila family of zinc-fnger architectural proteins, which also includes Su(Hw) and the conserved among higher eukaryotes CTCF. The architectural proteins maintain the active state of regulatory elements and the long-distance interactions between them. In particular, Pita is involved in the formation of several boundaries between regulatory domains that controlled the expression of three hox genes in the Bithorax complex (BX-C). The CP190 protein is recruited to chromatin through interaction with the architectural proteins. Results: Using in vitro pull-down analysis, we precisely mapped two unstructured regions of Pita that interact with the BTB domain of CP190. Then we constructed transgenic lines expressing the Pita protein of the wild-type and mutant variants lacking CP190-interacting regions. We have demonstrated that CP190-interacting region of the Pita can maintain nucleosome-free open chromatin and is critical for Pita-mediated enhancer blocking activity in BX-C. At the same time, interaction with CP190 is not required for the in vivo function of the mutant Pita protein, which binds to the same regions of the genome as the wild-type protein. -
Inhibition of MRN Activity by a Telomere Protein Motif
ARTICLE https://doi.org/10.1038/s41467-021-24047-2 OPEN Inhibition of MRN activity by a telomere protein motif Freddy Khayat1,6, Elda Cannavo2,6, Majedh Alshmery1, William R. Foster1, Charly Chahwan 1,4, Martino Maddalena1,5, Christopher Smith 1, Antony W. Oliver 1, Adam T. Watson1, Antony M. Carr 1, ✉ Petr Cejka2,3 & Alessandro Bianchi 1 The MRN complex (MRX in Saccharomyces cerevisiae, made of Mre11, Rad50 and Nbs1/Xrs2) 1234567890():,; initiates double-stranded DNA break repair and activates the Tel1/ATM kinase in the DNA damage response. Telomeres counter both outcomes at chromosome ends, partly by keeping MRN-ATM in check. We show that MRX is disabled by telomeric protein Rif2 through an N- terminal motif (MIN, MRN/X-inhibitory motif). MIN executes suppression of Tel1, DNA end- resection and non-homologous end joining by binding the Rad50 N-terminal region. Our data suggest that MIN promotes a transition within MRX that is not conductive for endonuclease activity, DNA-end tethering or Tel1 kinase activation, highlighting an Achilles’ heel in MRN, which we propose is also exploited by the RIF2 paralog ORC4 (Origin Recognition Complex 4) in Kluyveromyces lactis and the Schizosaccharomyces pombe telomeric factor Taz1, which is evolutionarily unrelated to Orc4/Rif2. This raises the possibility that analogous mechanisms might be deployed in other eukaryotes as well. 1 Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK. 2 Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Universitàdella Svizzera italiana (USI), Bellinzona, Switzerland. 3 Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), Zürich, Switzerland.