Promoter Regions
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis
Subject Review The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis Michalis V. Karamouzis,1 Panagiotis A. Konstantinopoulos,1,2 and Athanasios G. Papavassiliou1 1Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece and 2Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts Abstract Much of the current anticancer research effort is focused on Respiratory epithelium cancers are the leading cause cell-surface receptors and their cognate upstream molecules of cancer-related death worldwide. The multistep natural because they provide the easiest route for drugs to affect history of carcinogenesis can be considered as a cellular behavior, whereas agents acting at the level of gradual accumulation of genetic and epigenetic transcription need to invade the nucleus. However, the aberrations, resulting in the deregulation of cellular therapeutic effect of surface receptor manipulation might be homeostasis. Growing evidence suggests that cross- considered less than specific because their actions are talk between membrane and nuclear receptor signaling modulated by complex interacting downstream signal trans- pathways along with the activator protein-1 (AP-1) duction pathways. A pivotal transcription factor during cascade and its cofactor network represent a pivotal respiratory epithelium carcinogenesis is activator protein-1 molecular circuitry participating directly or indirectly in (AP-1). AP-1–regulated genes include important modulators of respiratory epithelium carcinogenesis. The crucial role invasion and metastasis, proliferation, differentiation, and of AP-1 transcription factor renders it an appealing survival as well as genes associated with hypoxia and target of future nuclear-directed anticancer therapeutic angiogenesis (7). Nuclear-directed therapeutic strategies might and chemoprevention approaches. -
DNA Sequencing and Sorting: Identifying Genetic Variations
BioMath DNA Sequencing and Sorting: Identifying Genetic Variations Student Edition Funded by the National Science Foundation, Proposal No. ESI-06-28091 This material was prepared with the support of the National Science Foundation. However, any opinions, findings, conclusions, and/or recommendations herein are those of the authors and do not necessarily reflect the views of the NSF. At the time of publishing, all included URLs were checked and active. We make every effort to make sure all links stay active, but we cannot make any guaranties that they will remain so. If you find a URL that is inactive, please inform us at [email protected]. DIMACS Published by COMAP, Inc. in conjunction with DIMACS, Rutgers University. ©2015 COMAP, Inc. Printed in the U.S.A. COMAP, Inc. 175 Middlesex Turnpike, Suite 3B Bedford, MA 01730 www.comap.com ISBN: 1 933223 71 5 Front Cover Photograph: EPA GULF BREEZE LABORATORY, PATHO-BIOLOGY LAB. LINDA SHARP ASSISTANT This work is in the public domain in the United States because it is a work prepared by an officer or employee of the United States Government as part of that person’s official duties. DNA Sequencing and Sorting: Identifying Genetic Variations Overview Each of the cells in your body contains a copy of your genetic inheritance, your DNA which has been passed down to you, one half from your biological mother and one half from your biological father. This DNA determines physical features, like eye color and hair color, and can determine susceptibility to medical conditions like hypertension, heart disease, diabetes, and cancer. -
Preinitiation Complex
Science Highlight – June 2011 Transcription Starts Here: Structural Models of a “Minimal” Preinitiation Complex RNA polymerase II (pol II) plays a central role in the regulation of gene expression. Pol II is the enzyme responsible for synthesizing all the messenger RNA (mRNA) and most of the small nuclear RNA (snRNA) in eukaryotes. One of the key questions for transcription is how pol II decides where to start on the genomic DNA to specifically and precisely turn on a gene. This is achieved during transcription initiation by concerted actions of the core enzyme pol II and a myriad of transcription factors including five general transcription factors, known as TFIIB, -D, -E, -F, -H, which together form a giant transcription preinitiation complex on a promoter prior to transcription. One of the most prominent core promoter DNA elements is the TATA box, usually directing transcription of tissue-specific genes. TATA-box binding protein (TBP), a key component of TFIID, recognizes the TATA DNA sequence. Based on the previous crystallographic studies, the TATA box DNA is bent by nearly 90 degree through the binding of TBP (1). This striking structural feature is thought to serve as a physical landmark for the location of active genes on the genome. In addition, the location of the TATA box at least in part determines the transcription start site (TSS) in most eukaryotes, including humans. The distance between the TATA box and the TSS is conserved at around 30 base pairs. TBP does not contact pol II directly and the TATA-containing promoter must be directed to the core enzyme through another essential transcription factor TFIIB. -
Targets TFIID and TFIIA to Prevent Activated Transcription
Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press The mammalian transcriptional repressor RBP (CBF1) targets TFIID and TFIIA to prevent activated transcription Ivan Olave, Danny Reinberg,1 and Lynne D. Vales2 Department of Biochemistry and 1Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 USA RBP is a cellular protein that functions as a transcriptional repressor in mammalian cells. RBP has elicited great interest lately because of its established roles in regulating gene expression, in Drosophila and mouse development, and as a component of the Notch signal transduction pathway. This report focuses on the mechanism by which RBP represses transcription and thereby regulates expression of a relatively simple, but natural, promoter. The results show that, irrespective of the close proximity between RBP and other transcription factors bound to the promoter, RBP does not occlude binding by these other transcription factors. Instead, RBP interacts with two transcriptional coactivators: dTAFII110, a subunit of TFIID, and TFIIA to repress transcription. The domain of dTAFII110 targeted by RBP is the same domain that interacts with TFIIA, but is disparate from the domain that interacts with Sp1. Repression can be thwarted when stable transcription preinitiation complexes are formed before RBP addition, suggesting that RBP interaction with TFIIA and TFIID perturbs optimal interactions between these coactivators. Consistent with this, interaction between RBP and TFIIA precludes interaction with dTAFII110. This is the first report of a repressor specifically targeting these two coactivators to subvert activated transcription. [Key Words: RBP; transcriptional repression; TFIIA/TFIID targeting] Received November 17, 1997; revised version accepted April 1, 1998. -
Repressor to Activator Switch by Mutations in the First Zn Finger of The
Proc. Nat!. Acad. Sci. USA Vol. 88, pp. 7086-7090, August 1991 Biochemistry Repressor to activator switch by mutations in the first Zn finger of the glucocorticoid receptor: Is direct DNA binding necessary? (interleukin 1 indudbility/dexamethasone modulation/DNA-binding domain mutants/interleukin 6 and c-fos promoters) ANURADHA RAY, K. STEVEN LAFORGE, AND PRAVINKUMAR B. SEHGAL* The Rockefeller University, New York, NY 10021 Communicated by Igor Tamm, May 20, 1991 (receivedfor review March 15, 1991) ABSTRACT Transfection ofHeLa cells with cDNA vectors previous experiments in HeLa cells transfected with cDNA expressing the wild-type human glucocorticoid receptor (GR) vectors constitutively expressing the wild type (wt) but not enabled dexamethasone to strongly repress cytokine- and sec- the inactive carboxyl-terminal truncation mutants of GR, we ond messenger-induced expression of cotransfected chimeric observed that dexamethasone (Dex) strongly repressed the reporter genes containing transcription regulatory DNA ele- induction by interleukin 1 (IL-1), tumor necrosis factor, ments from the human interleukin 6 (IL-6) promoter. Deletion phorbol ester, or forskolin of IL-6-chloramphenicol acetyl- of the DNA-binding domain or of the second Zn finger or a transferase (CAT) constructs containing IL-6 DNA from point mutation in the Zn catenation site in the second finger -225 to +13. Dex also repressed induction of IL-6- blocked the ability of GR to mediate repression of the IL-6 thymidine kinase (TK)-CAT chimeric constructs containing promoter. -
MINIREVIEW Catabolite Gene Activator Protein Activation of Lac Transcription WILLIAM S
JOURNAL OF BACTERIOLOGY, Feb. 1992, p. 655-658 Vol. 174, No. 3 0021-9193/92/030655-04$02.00/0 Copyright © 1992, American Society for Microbiology MINIREVIEW Catabolite Gene Activator Protein Activation of lac Transcription WILLIAM S. REZNIKOFF Department of Biochemistry, College ofAgricultural and Life Sciences, University of Wisconsin-Madison, 420 Henry Mall, Madison, Wisconsin 53706 CAP ACTIVATION OF lac TRANSCRIPTION upon binding, and this could lead to contact of upstream DNA with RNA polymerase (21, 25). What is the mechanism by which genes are positively Finally, CAP acts as a repressor in some systems (18, 26). regulated? How can several unlinked genes encoding related Since the lac promoter region (and other regulatory regions functions be regulated by a common signal? These are two of such as gal) contains several promoterlike elements which the questions which can be addressed by studying the overlap the promoter (Fig. 1), it was thought that CAP could catabolite gene activator protein (CAP). CAP responds to activate transcription by limiting the access of nonproduc- differences in the availability and nature of carbon sources, tive competitive promoterlike elements to RNA polymerase via variations in the intracellular concentration of cyclic (16). AMP (cAMP). CAP, when complexed with cAMP, is a sequence-specific DNA-binding protein which activates sev- WHY DIRECT CAP-RNA POLYMERASE CONTACTS eral gene systems and represses others. It has been most ARE PROBABLY IMPORTANT FOR lac ACTIVATION extensively studied for Escherichia coli, although closely related proteins exist in other gram-negative bacteria. Several lines of evidence indicate that direct CAP-RNA CAP is an important paradigm for understanding the polymerase contacts play an important role in lac activation. -
Molecular and Cellular Signaling
Martin Beckerman Molecular and Cellular Signaling With 227 Figures AIP PRESS 4(2) Springer Contents Series Preface Preface vii Guide to Acronyms xxv 1. Introduction 1 1.1 Prokaryotes and Eukaryotes 1 1.2 The Cytoskeleton and Extracellular Matrix 2 1.3 Core Cellular Functions in Organelles 3 1.4 Metabolic Processes in Mitochondria and Chloroplasts 4 1.5 Cellular DNA to Chromatin 5 1.6 Protein Activities in the Endoplasmic Reticulum and Golgi Apparatus 6 1.7 Digestion and Recycling of Macromolecules 8 1.8 Genomes of Bacteria Reveal Importance of Signaling 9 1.9 Organization and Signaling of Eukaryotic Cell 10 1.10 Fixed Infrastructure and the Control Layer 12 1.11 Eukaryotic Gene and Protein Regulation 13 1.12 Signaling Malfunction Central to Human Disease 15 1.13 Organization of Text 16 2. The Control Layer 21 2.1 Eukaryotic Chromosomes Are Built from Nucleosomes 22 2.2 The Highly Organized Interphase Nucleus 23 2.3 Covalent Bonds Define the Primary Structure of a Protein 26 2.4 Hydrogen Bonds Shape the Secondary Structure . 27 2.5 Structural Motifs and Domain Folds: Semi-Independent Protein Modules 29 xi xü Contents 2.6 Arrangement of Protein Secondary Structure Elements and Chain Topology 29 2.7 Tertiary Structure of a Protein: Motifs and Domains 30 2.8 Quaternary Structure: The Arrangement of Subunits 32 2.9 Many Signaling Proteins Undergo Covalent Modifications 33 2.10 Anchors Enable Proteins to Attach to Membranes 34 2.11 Glycosylation Produces Mature Glycoproteins 36 2.12 Proteolytic Processing Is Widely Used in Signaling 36 2.13 Reversible Addition and Removal of Phosphoryl Groups 37 2.14 Reversible Addition and Removal of Methyl and Acetyl Groups 38 2.15 Reversible Addition and Removal of SUMO Groups 39 2.16 Post-Translational Modifications to Histones . -
Polycomb Repressor Complex 2 Function in Breast Cancer (Review)
INTERNATIONAL JOURNAL OF ONCOLOGY 57: 1085-1094, 2020 Polycomb repressor complex 2 function in breast cancer (Review) COURTNEY J. MARTIN and ROGER A. MOOREHEAD Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1, Canada Received July 10, 2020; Accepted September 7, 2020 DOI: 10.3892/ijo.2020.5122 Abstract. Epigenetic modifications are important contributors 1. Introduction to the regulation of genes within the chromatin. The poly- comb repressive complex 2 (PRC2) is a multi‑subunit protein Epigenetic modifications, including DNA methylation complex that is involved in silencing gene expression through and histone modifications, play an important role in gene the trimethylation of lysine 27 at histone 3 (H3K27me3). The regulation. The dysregulation of these modifications can dysregulation of this modification has been associated with result in pathogenicity, including tumorigenicity. Research tumorigenicity through the increased repression of tumour has indicated an important influence of the trimethylation suppressor genes via condensing DNA to reduce access to the modification at lysine 27 on histone H3 (H3K27me3) within transcription start site (TSS) within tumor suppressor gene chromatin. This methylation is involved in the repression promoters. In the present review, the core proteins of PRC2, as of multiple genes within the genome by condensing DNA well as key accessory proteins, will be described. In addition, to reduce access to the transcription start site (TSS) within mechanisms controlling the recruitment of the PRC2 complex gene promoter sequences (1). The recruitment of H1.2, an H1 to H3K27 will be outlined. Finally, literature identifying the histone subtype, by the H3K27me3 modification has been a role of PRC2 in breast cancer proliferation, apoptosis and suggested as a mechanism for mediating this compaction (1). -
Identification of Promoter Regions in the Human Genome by Using a Retroviral Plasmid Library-Based Functional Reporter Gene Assa
Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Methods Identification of Promoter Regions in the Human Genome by Using a Retroviral Plasmid Library-Based Functional Reporter Gene Assay Shirin Khambata-Ford,1,5 Yueyi Liu,2 Christopher Gleason,1 Mark Dickson,3 Russ B. Altman,2 Serafim Batzoglou,4 and Richard M. Myers1,3,6 1Department of Genetics, 2Stanford Medical Informatics, 3Stanford Human Genome Center, Stanford University School of Medicine, Stanford, California 94305, USA; 4Department of Computer Science, Stanford University, Stanford, California 94305, USA Attempts to identify regulatory sequences in the human genome have involved experimental and computational methods such as cross-species sequence comparisons and the detection of transcription factor binding-site motifs in coexpressed genes. Although these strategies provide information on which genomic regions are likely to be involved in gene regulation, they do not give information on their functions. We have developed a functional selection for promoter regions in the human genome that uses a retroviral plasmid library-based system. This approach enriches for and detects promoter function of isolated DNA fragments in an in vitro cell culture assay. By using this method, we have discovered likely promoters of known and predicted genes, as well as many other putative promoter regions based on the presence of features such as CpG islands. Comparison of sequences of 858 plasmid clones selected by this assay with the human genome draft sequence indicates that a significantly higher percentage of sequences align to the 500-bp segment upstream of the transcription start sites of known genes than would be expected from random genomic sequences. -
Molecular Biology and Applied Genetics
MOLECULAR BIOLOGY AND APPLIED GENETICS FOR Medical Laboratory Technology Students Upgraded Lecture Note Series Mohammed Awole Adem Jimma University MOLECULAR BIOLOGY AND APPLIED GENETICS For Medical Laboratory Technician Students Lecture Note Series Mohammed Awole Adem Upgraded - 2006 In collaboration with The Carter Center (EPHTI) and The Federal Democratic Republic of Ethiopia Ministry of Education and Ministry of Health Jimma University PREFACE The problem faced today in the learning and teaching of Applied Genetics and Molecular Biology for laboratory technologists in universities, colleges andhealth institutions primarily from the unavailability of textbooks that focus on the needs of Ethiopian students. This lecture note has been prepared with the primary aim of alleviating the problems encountered in the teaching of Medical Applied Genetics and Molecular Biology course and in minimizing discrepancies prevailing among the different teaching and training health institutions. It can also be used in teaching any introductory course on medical Applied Genetics and Molecular Biology and as a reference material. This lecture note is specifically designed for medical laboratory technologists, and includes only those areas of molecular cell biology and Applied Genetics relevant to degree-level understanding of modern laboratory technology. Since genetics is prerequisite course to molecular biology, the lecture note starts with Genetics i followed by Molecular Biology. It provides students with molecular background to enable them to understand and critically analyze recent advances in laboratory sciences. Finally, it contains a glossary, which summarizes important terminologies used in the text. Each chapter begins by specific learning objectives and at the end of each chapter review questions are also included. -
Solutions for Practice Problems for Molecular Biology, Session 5
Solutions to Practice Problems for Molecular Biology, Session 5: Gene Regulation and the Lac Operon Question 1 a) How does lactose (allolactose) promote transcription of LacZ? 1) Lactose binds to the polymerase and increases efficiency. 2) Lactose binds to a repressor protein, and alters its conformation to prevent it from binding to the DNA and interfering with the binding of RNA polymerase. 3) Lactose binds to an activator protein, which can then help the RNA polymerase bind to the promoter and begin transcription. 4) Lactose prevents premature termination of transcription by directly binding to and bending the DNA. Solution: 2) Lactose binds to a repressor protein, and alters its conformation to prevent it from binding to the DNA and interfering with the binding of RNA polymerase. b) What molecule is used to signal low glucose levels to the Lac operon regulatory system? 1) Cyclic AMP 2) Calcium 3) Lactose 4) Pyruvate Solution: 1) Cyclic AMP. Question 2 You design a summer class where you recreate experiments studying the lac operon in E. coli (see schematic below). In your experiments, the activity of the enzyme b-galactosidase (β -gal) is measured by including X-gal and IPTG in the growth media. X-gal is a lactose analog that turns blue when metabolisize by b-gal, but it does not induce the lac operon. IPTG is an inducer of the lac operon but is not metabolized by b-gal. I O lacZ Plac Binding site for CAP Pi Gene encoding β-gal Promoter for activator protein Repressor (I) a) Which of the following would you expect to bind to β-galactosidase? Circle all that apply. -
Visualizing Transcription in Real-Time
Cent. Eur. J. Biol. • 3(1) • 2008 • 11-18 DOI: 10.2478/s11535-008-0001-1 Central European Journal of Biology Visualizing transcription in real-time Mini-Review Yehuda Brody, Yaron Shav-Tal* The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel Received 31 October 2007; Accepted 10 December 2007 Abstract: The transcriptional process is at the center of the gene expression pathway. In eukaryotes, the transcription of protein-coding genes into messenger RNAs is performed by RNA polymerase II. This enzyme is directed to bind at upstream gene sequences by the aid of transcription factors that assemble transcription-competent complexes. A series of biochemical and structural modifications render the polymerase transcriptionally active so that it can proceed from an initiation state into a functional elongating phase. Recent experi- mental efforts have attempted to visualize these processes as they take place on genes in living cells and to quantify the kinetics of in vivo transcription. Keywords: mRNA transcription • Nucleus • Live-cell imaging • Cellular dynamics © Versita Warsaw and Springer-Verlag Berlin Heidelberg. 1. Introduction review will describe the developments in the field of live-cell imaging that have allowed the analysis of mammalian RNA polymerase II transcription kinetics as The central dogma of molecular biology describes the they unfold in real-time. flow of information in the living cell from DNA to RNA to protein [1]. Information can also flow back from protein to nucleic acids. The fundamental process within this pathway that enables the mobility of genetic information 2. Lighting-up the nucleus from the stagnant DNA molecules contained within the cell nucleus to the ribosomal centers of protein Fluorescence microscopy provides the capability of translation and production in the cytoplasm is the following specific molecules as they are produced and process of messenger RNA (mRNA) transcription.