Sex Dependent Glial-Specific Changes in the Chromatin Accessibility
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Transcriptome Analysis of Four Arabidopsis Thaliana Mediator Tail Mutants Reveals Overlapping and Unique Functions in Gene Regulation
G3: Genes|Genomes|Genetics Early Online, published on July 26, 2018 as doi:10.1534/g3.118.200573 Title: Transcriptome Analysis of Four Arabidopsis thaliana Mediator Tail Mutants Reveals Overlapping and Unique Functions in Gene Regulation Authors: Whitney L. Dolan and Clint Chapple Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA and Purdue Center for Plant Biology, West Lafayette, IN 47907, USA. Reference numbers: Gene expression data are available in the Gene Expression Omnibus under accession GSE95574. 1 © The Author(s) 2013. Published by the Genetics Society of America. Running title: RNAseq of Four Arabidopsis MED Mutants Keywords: Mediator, Arabidopsis, transcription regulation, gene expression Corresponding author: Clint Chapple Department of Biochemistry Purdue University 175 South University St. West Lafayette, IN 47907 Telephone: 765-494-0494 Fax: 765-494-7897 E-mail: [email protected] 2 1 ABSTRACT 2 3 The Mediator complex is a central component of transcriptional regulation in Eukaryotes. The 4 complex is structurally divided into four modules known as the head, middle, tail and kinase 5 modules, and in Arabidopsis thaliana, comprises 28-34 subunits. Here, we explore the functions 6 of four Arabidopsis Mediator tail subunits, MED2, MED5a/b, MED16, and MED23, by comparing 7 the impact of mutations in each on the Arabidopsis transcriptome. We find that these subunits 8 affect both unique and overlapping sets of genes, providing insight into the functional and 9 structural relationships between them. The mutants primarily exhibit changes in the expression 10 of genes related to biotic and abiotic stress. We find evidence for a tissue specific role for 11 MED23, as well as in the production of alternative transcripts. -
Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces Cerevisiae Received: 26 October 2016 Henriette Uthe, Jens T
www.nature.com/scientificreports OPEN Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae Received: 26 October 2016 Henriette Uthe, Jens T. Vanselow & Andreas Schlosser Accepted: 25 January 2017 Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Published: 27 February 2017 Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis. The Mediator complex is an essential coactivator of eukaryotic transcription. Its major function is to communi- cate regulatory signals from gene-specific transcription factors upstream of the transcription start site to RNA Polymerase II (Pol II) and to promote activator-dependent assembly and stabilization of the preinitiation complex (PIC)1–3. The yeast Mediator complex is composed of 25 subunits and forms four distinct modules: the head, the middle, and the tail module, in addition to the four-subunit CDK8 kinase module (CKM), which can reversibly associate with the 21-subunit Mediator complex. -
UNIVERSITY of CALIFORNIA Los Angeles
UNIVERSITY OF CALIFORNIA Los Angeles Integrating molecular phenotypes and gene expression to characterize DNA variants for cardiometabolic traits A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Human Genetics by Alejandra Rodriguez 2018 ABSTRACT OF THE DISSERTATION Integrating molecular phenotypes and gene expression to characterize DNA variants for cardiometabolic traits by Alejandra Rodriguez Doctor of Philosophy in Human Genetics University of California, Los Angeles, 2018 Professor Päivi Elisabeth Pajukanta, Chair In-depth understanding of cardiovascular disease etiology requires characterization of its genetic, environmental, and molecular architecture. Genetic architecture can be defined as the characteristics of genetic variation responsible for broad-sense phenotypic heritability. Massively parallel sequencing has generated thousands of genomic datasets in diverse human tissues. Integration of such datasets using data mining methods has been used to extract biological meaning and has significantly advanced our understanding of the genome-wide nucleotide sequence, its regulatory elements, and overall chromatin architecture. This dissertation presents integration of “omics” data sets to understand the genetic architecture and molecular mechanisms of cardiovascular lipid disorders (further reviewed in Chapter 1). In 2013, Daphna Weissglas-Volkov and coworkers1 published an association between the chromosome 18q11.2 genomic region and hypertriglyceridemia in a genome-wide -
Microarray‑Based Identification of Nerve Growth‑Promoting Genes in Neurofibromatosis Type I
192 MOLECULAR MEDICINE REPORTS 9: 192-196, 2014 Microarray‑based identification of nerve growth‑promoting genes in neurofibromatosis type I YUFEI LIU1*, DONG KANG2*, CHUNYAN LI3, GUANG XU4, YAN TAN5 and JINHONG WANG6 1Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Jilin University, Changchun, Jilin 130000; 2Huiqiao Department, South Hospital of Southern Medical University, Guangdong 510630; Departments of 3Pediatric Respiratory and 4Infectious Diseases, The First Affiliated Hospital of Jilin University; 5Cancer Biotherapy Center, People's Hospital of Jilin Province, Changchun, Jilin 130000; 6Department of Respiratory, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China Received May 16, 2013; Accepted October 29, 2013 DOI: 10.3892/mmr.2013.1785 Abstract. As a genetic disease, neurofibromatosis patients, target molecules contributing to nerve growth during type 1 (NF1) is characterized by abnormalities in multiple NF1 development were investigated, which aided in improving tissues derived from the neural crest, including neoplasms in our understanding of this disease, and may provide a novel the ends of the limbs. The exact mechanism of nerve growth direction for nerve repair and regeneration. in NF1 is unclear. In the present study, the gene expression profile of nerves in healthy controls and NF1 patients with Introduction macrodactylia of the fingers or toes were analyzed in order to identify possible genes associated with nerve growth. The Neurofibromatosis is characterized by café-au-lait spots, Whole Human Genome Microarray was selected to screen for iris Lisch nodules and cutaneous or subcutaneous skin different gene expression profiles, and the result was analyzed tumors termedneurofibromas (1). -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
FBXL19 Recruits CDK-Mediator to Cpg Islands of Developmental Genes Priming Them for Activation During Lineage Commitment
RESEARCH ARTICLE FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment Emilia Dimitrova1, Takashi Kondo2†, Angelika Feldmann1†, Manabu Nakayama3, Yoko Koseki2, Rebecca Konietzny4‡, Benedikt M Kessler4, Haruhiko Koseki2,5, Robert J Klose1* 1Department of Biochemistry, University of Oxford, Oxford, United Kingdom; 2Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; 3Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan; 4Nuffield Department of Medicine, TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom; 5CREST, Japan Science and Technology Agency, Kawaguchi, Japan Abstract CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify *For correspondence: FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it [email protected] associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to †These authors contributed CpG island-associated promoters of non-transcribed developmental genes to prime these genes equally to this work for activation during cell lineage commitment. We further show that recognition of CpG islands by Present address: ‡Agilent FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric Technologies, Waldbronn, mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a Germany requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment. Competing interests: The DOI: https://doi.org/10.7554/eLife.37084.001 authors declare that no competing interests exist. -
Analysis of the Complex Interaction of Cdr1as‑Mirna‑Protein and Detection of Its Novel Role in Melanoma
ONCOLOGY LETTERS 16: 1219-1225, 2018 Analysis of the complex interaction of CDR1as‑miRNA‑protein and detection of its novel role in melanoma LIHUAN ZHANG*, YUAN LI*, WENYAN LIU, HUIFENG LI and ZHIWEI ZHU College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi 030801, P.R. China Received May 15, 2017; Accepted April 9, 2018 DOI: 10.3892/ol.2018.8700 Abstract. Despite improvements in the prevention, diagnosis has been detected in several species, including viruses (2), and treatment of melanoma having developed rapidly, the role plants (4), archaea (5)[Salzman, 2013 #198; Memczak, 2013 of circular RNA CDR1 antisense RNA (CDR1as) in melanoma #291] and animals (6). In eukaryotic cells, circRNA has remains to be elucidated. The aim of the present study was to attracted attention due to its unique characteristics, including predict the novel roles of CDR1as in melanoma through novel high stability, specificity and evolutionary conservation (7). bioinformatics analysis. In the present study, the circ2Traits The majority of circRNAs are derived from exons of coding database was used to supply information on CDR1as in cancer. regions, 3'UTRs, 5'UTRs, introns, intergenetic regions and CircNet, circBase and circInteractome databases were used to antisense RNAs (8). CircRNAs, which have attracted attention detect the co-expression of CDR1as, microRNAs and proteins. in recent years, can be produced by canonical and nonca- Furthermore, the functions and pathways of the associated nonical splicing as distinguished from the linear RNAs (9). proteins were predicted using the Database for Annotation, Through high-throughput sequencing, three types of circRNAs Visualization and Integrated Discovery. Gene Ontology have been identified: Exonic circRNAs (7), circular intronic enrichment analysis suggested that the proteins associated RNAs (ciRNAs) (9), and retained-intron circular RNAs or with CDR1as were mainly regulated in the cytoplasm as exon-intron circRNAs (elciRNAs) (10). -
Functional Studies of the Yeast Med5, Med15 and Med16 Mediator Tail Subunits
Functional Studies of the Yeast Med5, Med15 and Med16 Mediator Tail Subunits Miriam Larsson1, Hanna Uvell1¤a, Jenny Sandstro¨ m1, Patrik Ryde´n2, Luke A. Selth3¤b, Stefan Bjo¨ rklund1* 1 Department of Medical Biochemistry and Biophysics, Umea˚ University, Umea˚, Sweden, 2 Department of Statistics, Umea˚ University, Umea˚, Sweden, 3 Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, United Kingdom Abstract The yeast Mediator complex can be divided into three modules, designated Head, Middle and Tail. Tail comprises the Med2, Med3, Med5, Med15 and Med16 protein subunits, which are all encoded by genes that are individually non-essential for viability. In cells lacking Med16, Tail is displaced from Head and Middle. However, inactivation of MED5/MED15 and MED15/ MED16 are synthetically lethal, indicating that Tail performs essential functions as a separate complex even when it is not bound to Middle and Head. We have used the N-Degron method to create temperature-sensitive (ts) mutants in the Mediator tail subunits Med5, Med15 and Med16 to study the immediate effects on global gene expression when each subunit is individually inactivated, and when Med5/15 or Med15/16 are inactivated together. We identify 25 genes in each double mutant that show a significant change in expression when compared to the corresponding single mutants and to the wild type strain. Importantly, 13 of the 25 identified genes are common for both double mutants. We also find that all strains in which MED15 is inactivated show down-regulation of genes that have been identified as targets for the Ace2 transcriptional activator protein, which is important for progression through the G1 phase of the cell cycle. -
Control of Free Arachidonic Acid Levels by Phospholipases A2 And
Control of Free Arachidonic Acid Levels by Phospholipases A2 and Lysophospholipid Acyltransferases Gema Pérez-Chacón, Alma M. Astudillo, David Balgoma, María A. Balboa, and Jesús Balsinde* Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain, and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain *Corresponding author. Phone, +34-983-423-062; Fax, +34-983-184-800; e-mail: [email protected] Keywords: Arachidonic Acid; Phospholipase A2; Free fatty acid; Eicosanoids; Acyltransferase; Phospholipid Remodeling. Running Title: Control of Arachidonic Acid Levels 1 Abstract Arachidonic acid (AA) and its oxygenated derivatives, collectively known as the eicosanoids, are key mediators of a wide variety of physiological and pathophysiological states. AA, obtained from the diet or synthesized from linoleic acid, is rapidly incorporated into cellular phospholipids by the concerted action of arachidonoyl-CoA synthetase and lysophospholipid acyl transferases. Under the appropriate conditions, AA is liberated from its phospholipid storage sites by the action of one or various phospholipase A2 enzymes. Thus, cellular availability of AA, and hence the amount of eicosanoids produced, depends on an exquisite balance between phospholipid reacylation and hydrolysis reactions. This review focus on the enzyme families that are involved in these reactions in resting and stimulated cells. Abbreviations AA, arachidonic -
Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis
Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you. -
Ketogenesis Activates Metabolically Protective Γδ T Cells in Visceral Adipose Tissue
ARTICLES https://doi.org/10.1038/s42255-019-0160-6 Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue Emily L. Goldberg1,2, Irina Shchukina3, Jennifer L. Asher1, Sviatoslav Sidorov1, Maxim N. Artyomov 3 and Vishwa Deep Dixit1,2* Ketone bodies are essential alternative fuels that allow humans to survive periods of glucose scarcity induced by starvation and prolonged exercise. A widely used ketogenic diet (KD), which is extremely high in fat with very low carbohydrates, drives the host into using β-hydroxybutyrate for the production of ATP and lowers NLRP3-mediated inflammation. However, the extremely high fat composition of KD raises the question of how ketogenesis affects adipose tissue to control inflammation and energy homeostasis. Here, by using single-cell RNA sequencing of adipose-tissue-resident immune cells, we show that KD expands metabolically protective γδ T cells that restrain inflammation. Notably, long-term ad libitum KD feeding in mice causes obesity, impairs metabolic health and depletes the adipose-resident γδ T cells. In addition, mice lacking γδ T cells have impaired glucose homeostasis. Our results suggest that γδ T cells are mediators of protective immunometabolic responses that link fatty acid–driven fuel use to reduced adipose tissue inflammation. iets with limited carbohydrate content induce a metabolic sensor expressed in innate immune cells that provides a scaffold switch to fatty acid metabolism whereby the host produces for caspase 1 activation, enabling cleavage and secretion of IL-1β and uses ketone bodies to meet energetic demands. The KD and IL-18. Elevated NLRP3-dependent caspase 1 activation can be D −/− is an extremely high-fat, very low-carbohydrate diet in which ~90% detected in visceral white adipose tissue of obese mice, and Nlrp3 of calories come from fat and <1% of calories from carbohydrate, mice are protected from obesity-induced inflammatory diseases thus limiting glucose availability and forcing this metabolic adapta- including glucose intolerance and hepatic steatosis16. -
By IL-4 in Memory CD8 T Cells Negative Regulation of NKG2D
Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells Erwan Ventre, Lilia Brinza, Stephane Schicklin, Julien Mafille, Charles-Antoine Coupet, Antoine Marçais, Sophia This information is current as Djebali, Virginie Jubin, Thierry Walzer and Jacqueline of October 2, 2021. Marvel J Immunol published online 31 August 2012 http://www.jimmunol.org/content/early/2012/08/31/jimmun ol.1102954 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2012/09/04/jimmunol.110295 Material 4.DC1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 2, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published August 31, 2012, doi:10.4049/jimmunol.1102954 The Journal of Immunology Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells Erwan Ventre, Lilia Brinza,1 Stephane Schicklin,1 Julien Mafille, Charles-Antoine Coupet, Antoine Marc¸ais, Sophia Djebali, Virginie Jubin, Thierry Walzer, and Jacqueline Marvel IL-4 is one of the main cytokines produced during Th2-inducing pathologies.