Differential Gene Expression and Specific Gene Duplications
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Calumenin-15 Facilitates Filopodia Formation by Promoting TGF-Β Superfamily Cytokine GDF-15 Transcription
Citation: Cell Death and Disease (2013) 4, e870; doi:10.1038/cddis.2013.403 OPEN & 2013 Macmillan Publishers Limited All rights reserved 2041-4889/13 www.nature.com/cddis Calumenin-15 facilitates filopodia formation by promoting TGF-b superfamily cytokine GDF-15 transcription H Feng1,3, L Chen1,3, Q Wang1,3, B Shen1, L Liu1, P Zheng1,SXu1, X Liu1, J Chen1,2 and J Teng*,1 Filopodia, which are actin-rich finger-like membrane protrusions, have an important role in cell migration and tumor metastasis. Here we identify 13 novel calumenin (Calu) isoforms (Calu 3–15) produced by alternative splicing, and find that Calu-15 promotes filopodia formation and cell migration. Calu-15 shuttles between the nucleus and cytoplasm through interacting with importin a, Ran GTPase, and Crm1. The phosphorylation of the threonine at position 73 (Thr-73) by casein kinase 2 (CK2) is essential for the nuclear import of Calu-15, and either Thr-73 mutation or inhibition of CK2 interrupts its nuclear localization. In the nucleus, Calu-15 increases the transcription of growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-b (TGF-b) superfamily, via binding to its promoter region. Furthermore, Calu-15 induces filopodia formation mediated by GDF-15. Together, we identify that Calu-15, a novel isoform of Calu with phosphorylation-dependent nuclear localization, has a critical role in promoting filopodia formation and cell migration by upregulating the GDF-15 transcription. Cell Death and Disease (2013) 4, e870; doi:10.1038/cddis.2013.403; published -
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. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Comparative Genome Mapping in the Sequence-Based Era: Early Experience with Human Chromosome 7
Downloaded from genome.cshlp.org on May 28, 2019 - Published by Cold Spring Harbor Laboratory Press First Glimpses/Report Comparative Genome Mapping in the Sequence-based Era: Early Experience with Human Chromosome 7 James W. Thomas,1 Tyrone J. Summers,1 Shih-Queen Lee-Lin,1 Valerie V. Braden Maduro,1 Jacquelyn R. Idol,1 Stephen D. Mastrian,1 Joseph F. Ryan,1 D. Curtis Jamison,1 and Eric D. Green1,2 1Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 USA The success of the ongoing Human Genome Project has resulted in accelerated plans for completing the human genome sequence and the earlier-than-anticipated initiation of efforts to sequence the mouse genome. As a complement to these efforts, we are utilizing the available human sequence to refine human-mouse comparative maps and to assemble sequence-ready mouse physical maps. Here we describe how the first glimpses of genomic sequence from human chromosome 7 are directly facilitating these activities. Specifically, we are actively enhancing the available human-mouse comparative map by analyzing human chromosome 7 sequence for the presence of orthologs of mapped mouse genes. Such orthologs can then be precisely positioned relative to mapped human STSs and other genes. The chromosome 7 sequence generated to date has allowed us to more than double the number of genes that can be placed on the comparative map. The latter effort reveals that human chromosome 7 is represented by at least 20 orthologous segments of DNA in the mouse genome. A second component of our program involves systematically analyzing the evolving human chromosome 7 sequence for the presence of matching mouse genes and expressed-sequence tags (ESTs). -
A Model for Profiling the Emolecular Effects of Alcohol
The Pharmacogenomics Journal (2015) 15, 177–188 © 2015 Macmillan Publishers Limited All rights reserved 1470-269X/15 www.nature.com/tpj ORIGINAL ARTICLE The synaptoneurosome transcriptome: a model for profiling the emolecular effects of alcohol D Most1,2, L Ferguson1,2, Y Blednov1, RD Mayfield1 and RA Harris1 Chronic alcohol consumption changes gene expression, likely causing persistent remodeling of synaptic structures via altered translation of mRNAs within synaptic compartments of the cell. We profiled the transcriptome from synaptoneurosomes (SNs) and paired total homogenates (THs) from mouse amygdala following chronic voluntary alcohol consumption. In SN, both the number of alcohol-responsive mRNAs and the magnitude of fold-change were greater than in THs, including many GABA-related mRNAs upregulated in SNs. Furthermore, SN gene co-expression analysis revealed a highly connected network, demonstrating coordinated patterns of gene expression and highlighting alcohol-responsive biological pathways, such as long-term potentiation, long-term depression, glutamate signaling, RNA processing and upregulation of alcohol-responsive genes within neuroimmune modules. Alterations in these pathways have also been observed in the amygdala of human alcoholics. SNs offer an ideal model for detecting intricate networks of coordinated synaptic gene expression and may provide a unique system for investigating therapeutic targets for the treatment of alcoholism. The Pharmacogenomics Journal (2015) 15, 177–188; doi:10.1038/tpj.2014.43; published online 19 August 2014 INTRODUCTION mRNAs from SN15,16,18,19 and TH samples from mouse amygdala, a Alcohol dependence is a severe and widespread disease. Over 17 brain region known to be involved with the negative reinforce- 20 million Americans suffer from alcohol-related problems; total cost ment of alcohol and other drugs of abuse. -
11991 Calumenin (4C6) Mouse Mab
Revision 1 C 0 2 - t Calumenin (4C6) Mouse mAb a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 1 9 9 Web: [email protected] 1 www.cellsignal.com 1 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source/Isotype: UniProt ID: Entrez-Gene Id: WB, IF-IC H M R Mk Endogenous 47 Mouse IgG1 O43852 813 Product Usage Information Application Dilution Western Blotting 1:1000 Immunofluorescence (Immunocytochemistry) 1:50 Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% sodium azide. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity Calumenin (4C6) Mouse mAb recognizes endogenous levels of total calumenin protein. Species Reactivity: Human, Mouse, Rat, Monkey Source / Purification Monoclonal antibody is produced by immunizing animals with a recombinant protein specific to the carboxy terminus of human calumenin protein. Background Calumenin belongs to the CREC family of proteins that also contains reticulocalbin, ERC- 55/TCBP-49/E6BP, Cab45, and crocalbin/CBP-50. These EF-hand proteins localize to the endoplasmic reticulum (ER) and are involved in the secretory pathway in mammalian cells (1). Calumenin exists as two isoforms corresponding to alternativly spliced variants of the CALU gene (2). Calumenin has been shown to localize to the ER via a carboxy terminal HDEF ER retention signal (3), and undergoes secretion after trafficking through the secretory pathway (4). Secreted calumenin plays a role in amyloidosis by interacting with serum amyloid P component (5). -
The Intracellular Transport and Secretion of Calumenin- 1/2 in Living Cells
The Intracellular Transport and Secretion of Calumenin- 1/2 in Living Cells Qiao Wang1., Hui Feng1., Pengli Zheng1., Birong Shen1, Liang Chen1, Lin Liu1, Xiao Liu1, Qingsong Hao1, Shunchang Wang1, Jianguo Chen1,2, Junlin Teng1* 1 State Key Laboratory of Bio-membrane and Membrane Bio-engineering and Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China, 2 Center for Theoretical Biology, Peking University, Beijing, China Abstract Calumenin isoforms 1 and 2 (calu-1/2), encoded by the CALU gene, belong to the CREC protein family. Calu-1/2 proteins are secreted into the extracellular space, but the secretory process and regulatory mechanism are largely unknown. Here, using a time-lapse imaging system, we visualized the intracellular transport and secretory process of calu-1/2-EGFP after their translocation into the ER lumen. Interestingly, we observed that an abundance of calu-1/2-EGFP accumulated in cellular processes before being released into the extracellular space, while only part of calu-1/2-EGFP proteins were secreted directly after attaching to the cell periphery. Moreover, we found the secretion of calu-1/2-EGFP required microtubule integrity, and that calu-1/2-EGFP-containing vesicles were transported by the motor proteins Kif5b and cytoplasmic dynein. Finally, we determined the export signal of calu-1/2-EGFP (amino acid positions 20–46) and provided evidence that the asparagine at site 131 was indispensable for calu-1/2-EGFP stabilization. Taken together, we provide a detailed picture of the intracellular transport of calu-1/2-EGFP, which facilitates our understanding of the secretory mechanism of calu-1/2. -
The Genetics of Bipolar Disorder
Molecular Psychiatry (2008) 13, 742–771 & 2008 Nature Publishing Group All rights reserved 1359-4184/08 $30.00 www.nature.com/mp FEATURE REVIEW The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions A Serretti and L Mandelli Institute of Psychiatry, University of Bologna, Bologna, Italy Bipolar disorder (BP) is a complex disorder caused by a number of liability genes interacting with the environment. In recent years, a large number of linkage and association studies have been conducted producing an extremely large number of findings often not replicated or partially replicated. Further, results from linkage and association studies are not always easily comparable. Unfortunately, at present a comprehensive coverage of available evidence is still lacking. In the present paper, we summarized results obtained from both linkage and association studies in BP. Further, we indicated new potential interesting genes, located in genome ‘hot regions’ for BP and being expressed in the brain. We reviewed published studies on the subject till December 2007. We precisely localized regions where positive linkage has been found, by the NCBI Map viewer (http://www.ncbi.nlm.nih.gov/mapview/); further, we identified genes located in interesting areas and expressed in the brain, by the Entrez gene, Unigene databases (http://www.ncbi.nlm.nih.gov/entrez/) and Human Protein Reference Database (http://www.hprd.org); these genes could be of interest in future investigations. The review of association studies gave interesting results, as a number of genes seem to be definitively involved in BP, such as SLC6A4, TPH2, DRD4, SLC6A3, DAOA, DTNBP1, NRG1, DISC1 and BDNF. -
The Genetic Architecture of Down Syndrome Phenotypes Revealed by High-Resolution Analysis of Human Segmental Trisomies
The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies Jan O. Korbela,b,c,1, Tal Tirosh-Wagnerd,1, Alexander Eckehart Urbane,f,1, Xiao-Ning Chend, Maya Kasowskie, Li Daid, Fabian Grubertf, Chandra Erdmang, Michael C. Gaod, Ken Langeh,i, Eric M. Sobelh, Gillian M. Barlowd, Arthur S. Aylsworthj,k, Nancy J. Carpenterl, Robin Dawn Clarkm, Monika Y. Cohenn, Eric Dorano, Tzipora Falik-Zaccaip, Susan O. Lewinq, Ira T. Lotto, Barbara C. McGillivrayr, John B. Moeschlers, Mark J. Pettenatit, Siegfried M. Pueschelu, Kathleen W. Raoj,k,v, Lisa G. Shafferw, Mordechai Shohatx, Alexander J. Van Ripery, Dorothy Warburtonz,aa, Sherman Weissmanf, Mark B. Gersteina, Michael Snydera,e,2, and Julie R. Korenbergd,h,bb,2 Departments of aMolecular Biophysics and Biochemistry, eMolecular, Cellular, and Developmental Biology, and fGenetics, Yale University School of Medicine, New Haven, CT 06520; bEuropean Molecular Biology Laboratory, 69117 Heidelberg, Germany; cEuropean Molecular Biology Laboratory (EMBL) Outstation Hinxton, EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; dMedical Genetics Institute, Cedars–Sinai Medical Center, Los Angeles, CA 90048; gDepartment of Statistics, Yale University, New Haven, CT 06520; Departments of hHuman Genetics, and iBiomathematics, University of California, Los Angeles, CA 90095; Departments of jPediatrics and kGenetics, University of North Carolina, Chapel Hill, NC 27599; lCenter for Genetic Testing, -
WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2012/174282 A2 20 December 2012 (20.12.2012) P O P C T (51) International Patent Classification: David [US/US]; 13539 N . 95th Way, Scottsdale, AZ C12Q 1/68 (2006.01) 85260 (US). (21) International Application Number: (74) Agent: AKHAVAN, Ramin; Caris Science, Inc., 6655 N . PCT/US20 12/0425 19 Macarthur Blvd., Irving, TX 75039 (US). (22) International Filing Date: (81) Designated States (unless otherwise indicated, for every 14 June 2012 (14.06.2012) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, English (25) Filing Language: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, Publication Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (30) Priority Data: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 61/497,895 16 June 201 1 (16.06.201 1) US MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 61/499,138 20 June 201 1 (20.06.201 1) US OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, 61/501,680 27 June 201 1 (27.06.201 1) u s SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 61/506,019 8 July 201 1(08.07.201 1) u s TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Chromosome 21 Leading Edge Gene Set
Chromosome 21 Leading Edge Gene Set Genes from chr21q22 that are part of the GSEA leading edge set identifying differences between trisomic and euploid samples. Multiple probe set IDs corresponding to a single gene symbol are combined as part of the GSEA analysis. Gene Symbol Probe Set IDs Gene Title 203865_s_at, 207999_s_at, 209979_at, adenosine deaminase, RNA-specific, B1 ADARB1 234539_at, 234799_at (RED1 homolog rat) UDP-Gal:betaGlcNAc beta 1,3- B3GALT5 206947_at galactosyltransferase, polypeptide 5 BACE2 217867_x_at, 222446_s_at beta-site APP-cleaving enzyme 2 1553227_s_at, 214820_at, 219280_at, 225446_at, 231860_at, 231960_at, bromodomain and WD repeat domain BRWD1 244622_at containing 1 C21orf121 240809_at chromosome 21 open reading frame 121 C21orf130 240068_at chromosome 21 open reading frame 130 C21orf22 1560881_a_at chromosome 21 open reading frame 22 C21orf29 1552570_at, 1555048_at_at, 1555049_at chromosome 21 open reading frame 29 C21orf33 202217_at, 210667_s_at chromosome 21 open reading frame 33 C21orf45 219004_s_at, 228597_at, 229671_s_at chromosome 21 open reading frame 45 C21orf51 1554430_at, 1554432_x_at, 228239_at chromosome 21 open reading frame 51 C21orf56 223360_at chromosome 21 open reading frame 56 C21orf59 218123_at, 244369_at chromosome 21 open reading frame 59 C21orf66 1555125_at, 218515_at, 221158_at chromosome 21 open reading frame 66 C21orf7 221211_s_at chromosome 21 open reading frame 7 C21orf77 220826_at chromosome 21 open reading frame 77 C21orf84 239968_at, 240589_at chromosome 21 open reading frame 84 -
Language Impairment Resulting from a De Novo Deletion of 7Q32.1-Q33: a Case
bioRxiv preprint doi: https://doi.org/10.1101/047241; this version posted April 6, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Language impairment resulting from a de novo deletion of 7q32.1-q33: a case report Mª Salud Jiménez-Romero, Montserrat Barcos-Martínez, Isabel Espejo-Portero, Antonio Benítez-Burraco Corresponding author: Antonio Benítez-Burraco, PhD. Department of Spanish Philology and its Didactics, University of Huelva, Huelva, Spain e-mail: [email protected] Affiliations for the other authors: Mª Salud Jiménez-Romero: Department of Psychology, University of Córdoba, Córdoba, Spain & Maimónides Institute of Biomedical Research, Córdoba, Spain Montserrat Barcos-Martínez: Laboratory of Molecular Genetics, University Hospital “Reina Sofía”, Córdoba, Spain &Maimónides Institute of Biomedical Research, Córdoba, Spain Isabel Espejo-Portero: Laboratory of Molecular Genetics, University Hospital “Reina Sofía”, Córdoba, Spain & Maimónides Institute of Biomedical Research, Córdoba, Spain bioRxiv preprint doi: https://doi.org/10.1101/047241; this version posted April 6, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 2 ABSTRACT Chromosome 7 is a hot spot for cognitive disorders involving language deficits. We report on a girl who presents with a cognitive and speech delay, motor problems, hearing loss, and behavioral disturbances, and a de novo deletion within 7q32.1-q33 (chromosome position: chr7:127109685-132492196, hg 18). Several genes involved in brain development and function are located within the deleted region.