DOCSLIB.ORG

Handbook of Epigenetics: the New Molecular and Medical Genetics

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Handbook of Epigenetics: the New Molecular and Medical Genetics CHAPTER 21 Epigenetics, Stem Cells, Cellular Differentiation, and Associated Hereditary Neurological Disorders Bhairavi Srinageshwar*, Panchanan Maiti*,**, Gary L. Dunbar*,**, Julien Rossignol* *Central Michigan University, Mt. Pleasant, MI, United States; **Field Neurosciences Institute, Saginaw, MI, United States OUTLINE Introduction to Epigenetics 323 Histones and Their Structure 325 Epigenetics and Neurological Disorders 326 Epigenetics and the Human Brain 324 Stem Cells 324 Conclusions 335 Eukaryotic Chromosomal Organization 325 References 336 INTRODUCTION TO EPIGENETICS changes are discussed in detail elsewhere [3,4], but are briefly described later as an overview for this chapter. Epigenetics is defined as structural and functional DNA methylation. DNA methylation and some of the changes occurring in histones and DNA, in the absence histone modifications are interdependent and play an of alterations of the DNA sequence, which, in turn, has important role in gene activation and repression during a significant impact on how gene expression is altered development [5]. DNA methylation reactions are cata- in a cell [1]. The term “epigenetics” was coined by the lyzed by a family of enzymes called DNA methyl trans- famous developmental biologist, Cornard Hal Wad- ferases (DNMTs), which add methyl groups to a cytosine dington, as “the branch of biology that studies the causal base of the DNA at the 5’-end, giving rise to the 5’-methyl interactions between genes and their products, which cytosine. This reaction can either activate or repress gene bring the phenotype into being”[2]. Epigenetics bridge expression, depending on the site of methylation and it the gap between the environment and gene expression, can also determine how well the enzymes for gene tran- which was once believed to function independently [3]. scription can access the DNA that is wrapped around the Epigenetic changes can lead to increase or decrease in histone [6]. gene expression, thereby activating and/or deactivating Histone methylation. Trimethylation of lysine at position genes, depending on the nature of the epigenetic con- 4 on histone 3 (H3K4me3) promotes gene transcription trol. Some of the most important histone modifications (i.e., gene activation), whereas trimethylation of lysine include: (1) methylation; (2) acetylation; (3) phosphory- at position 27 on histone 3 (H3K27me3) inhibits gene lation; (4) ubiquitination; and (5) SUMOylation and transcription (i.e., gene silencing). Alternate gene acti- DNA modification, including DNA methylation. These vation and repression promote a balanced dose of gene Handbook of Epigenetics. http://dx.doi.org/10.1016/B978-0-12-805388-1.00021-3 Copyright © 2017 Elsevier Inc. All rights reserved. 323 324 21. EPIGENETICS, STEM CELLS, CELLULAR Differentiation, AND Associated Hereditary NEUROLOGICAL Disorders expression, which is required for those genes involved in The outer layer of the embryo, called ectoderm, forms overall development and maturation of organisms. This the central nervous system, and during the process of ensures that only appropriate genes are turned “ON” development, DNA methylation controls the epigen- and “OFF” at any given point of time [7]. Huntington’s etic mechanisms of the embryonic cells. For example, disease (HD), Parkinson’s disease (PD), and multiple to prevent the differentiation of nonneuronal cells into sclerosis (MS) are some of the diseases that are caused by mature neurons, the proneural genes, as well as gene abnormal DNA methylation pattern. These are discussed which are associated with proteins involved with neu- in more detail in later sections of this chapter. rogenesis, such as the brain-derived neurotrophic factor Histone acetylation. DNA acetylation involves the (BDNF) gene, are silenced by DNA methylation at their acetylation of lysine residue, which is catalyzed by the promoter region. However, DNA remethylation can enzymes, histone acetyltransferases (HATs), and histone take place on a neuronal gene, such as Sox2 [11], which deacetylases (HDACs), which have opposing effects on allows for the selective initiation of neuronal develop- each other. HATs transfer acetyl groups to lysine, whereas ment. Similarly, during initial development of the cor- HDACs remove acetyl groups from lysine. However, tex, the genes involved in the formation of glial cells are presence or absence of an acetyl group (CH3CO) on a suppressed by DNA methylation, promoting the forma- lysine residue alters the charge on the amino acid and tion of more neurons during the early stages of neuro- can decrease the interaction of the N-terminal region of nal development. Eventually, during the later stages of histones with the negatively charged phosphate groups cortical development, the DNA methylation is reversed, of DNA. These events are involved in transformation of leading to the generation of glial cells [12,13]. Some of the condensed chromatin into a more relaxed structure, the genes involved in postnatal neurogenesis are Sox2, which can induce gene expression [8]. Dlx2, Sp8, and Neurog2 and those involved in the for- Histone phosphorylation. Phosphorylation involves addi- mation of glial cells are Sparcl1 and Nkx2-2. It has been tion of phosphate group to threonine, serine, and tyrosine shown that during the differentiation of neural stem residues. Phosphorylation of serine at position 139 on cells (NSCs) or progenitor cells, DNA methylation is histone 2 (H2) occurs as a response to DNA damage dur- facilitated by DNMT3a, which silences the genes Sparcl1 ing cell cycling. This relaxes the chromatin; thereby the and Nkx2-2, leading to the inhibition of glial cell for- proteins or factors responsible for repairing the damaged mation and promotion of mature neuron development regions of the DNA have greater access to the DNA, which from NSCs [14]. It is also believed that the normal aging aids in the recovery of the DNA damage. Moreover, phos- process in humans is associated with modification of the phorylation of threonine and serine residues on histone 3 epigenome in the brain, affecting certain genes related (H3) facilitates regulation of gene expression [9]. Histidine to neurogenesis, especially within the cortex [15]. This phosphorylation is one of the epigenetic modifications process leads to the disruption of synapses, abnormal occurring in the prokaryotic cells and in lower eukaryotes neurotransmission, and is associated to age-related dis- that plays a major role in cell signaling. The histidine is orders [16]. However, a comprehensive description of phosphorylated at the imidazole ring, but occurs only on the epigenetic mechanisms related to aging is beyond those nitrogen atoms that are unprotonated [10]. the scope of this chapter. Histone ubiquitination and SUMOylation. Ubiquitina- tion and SUMOylation are associated with posttransla- tional modifications that regulate transcription of gene Stem Cells and protein translation activities. It is well established Dysregulation of epigenetic mechanisms has a direct that the addition of ubiquitin molecules to proteins facil- impact on gene expression patterns that lead to abnor- itate targeted protein degradation. In addition to ubiqui- mal gene functions, which form the basis of most of the tin, various small ubiquitin-like molecules (SUMO) are genetic disorders (monogenic or polygenic) in humans. observed in cells, known as small ubiquitin-related mod- Environmental stress can also alter epigenetic mecha- ifier. These molecules have activities, which are similar nisms, which could become a cause for the predisposi- to ubiquitin and can attach covalently to those proteins, tion of certain diseases, such as autism, schizophrenia, which are involved in changing chromatin structure and and congenital heart disease [17]. This chapter focuses gene expression [3]. on the role of epigenetics and epigenetic changes that take place during stem cell differentiation, which can be used as a potential therapy for neurological diseases. EPIGENETICS AND THE HUMAN BRAIN Stem cells have a unique property of proliferation, dif- ferentiation, and self-renewal. Stem cell plasticity is an Generation of neurons and glial cells from progeni- important characteristic and is based on the degree of tor cells involve epigenetic mechanisms that take place pluripotency, which is the ability of a cell to differenti- throughout the developmental stages of the brain. ate into another cell lineage. Stem cells can be classified V. Factors INFLUENCING EPIGENETIC CHANGES EPIGENETICS AND THE HUMAN BRAIN 325 TABLE 21.1 An Overview of Various Epigenetic Mechanisms Associated With Neurodegenerative Diseases Neurodegenerative disease Stem cell based therapy Epigenetic mechanism involved with disease HD BM-MSCs Histone 3 (H3) methylation leading to reduced trophic factors [20] PD NSCs DNA methylation leading to metabolic defects [21] RTT iPSCs Point mutations in MeCP2 gene leading to defective epigenetic regulatory molecules [22] SCA UC-MSCs Methylation and acetylation of histone leading to reduced RNA expression [23,24] MS HSCs DNA methylation, histone acetylation and posttranscriptional modification by miRNA leading to compromised immune response [25–27] HD, Huntington’s disease; MS, multiple sclerosis; PD, Parkinson’s disease; RTT, Rett syndrome; SCA, spinocerebellar ataxias. as: (1) totipotent, such as embryonic stem cells (ESCs) chromosomes, and the general hierarchy in the chromo- of the morula, which can be differentiated into any cell somal organization, is needed, which
Load more

Recommended publications
  • Intelligent Design, Abiogenesis, and Learning from History: Dennis R
    Author Exchange Intelligent Design, Abiogenesis, and Learning from History: Dennis R. Venema A Reply to Meyer Dennis R. Venema Weizsäcker’s book The World View of Physics is still keeping me very busy. It has again brought home to me quite clearly how wrong it is to use God as a stop-gap for the incompleteness of our knowledge. If in fact the frontiers of knowledge are being pushed back (and that is bound to be the case), then God is being pushed back with them, and is therefore continually in retreat. We are to find God in what we know, not in what we don’t know; God wants us to realize his presence, not in unsolved problems but in those that are solved. Dietrich Bonhoeffer1 am thankful for this opportunity to nature, is the result of intelligence. More- reply to Stephen Meyer’s criticisms over, this assertion is proffered as the I 2 of my review of his book Signature logical basis for inferring design for the in the Cell (hereafter Signature). Meyer’s origin of biological information: if infor- critiques of my review fall into two gen- mation only ever arises from intelli- eral categories. First, he claims I mistook gence, then the mere presence of Signature for an argument against bio- information demonstrates design. A few logical evolution, rendering several of examples from Signature make the point my arguments superfluous. Secondly, easily: Meyer asserts that I have failed to refute … historical scientists can show that his thesis by not providing a “causally a presently acting cause must have adequate alternative explanation” for the been present in the past because the origin of life in that the few relevant cri- proposed candidate is the only known tiques I do provide are “deeply flawed.” cause of the effect in question.
    [Show full text]
  • Ecological Developmental Biology and Disease States CHAPTER 5 Teratogenesis: Environmental Assaults on Development 167
    Integrating Epigenetics, Medicine, and Evolution Scott F. Gilbert David Epel Swarthmore College Hopkins Marine Station, Stanford University Sinauer Associates, Inc. • Publishers Sunderland, Massachusetts U.S.A. © Sinauer Associates, Inc. This material cannot be copied, reproduced, manufactured or disseminated in any form without express written permission from the publisher. Brief Contents PART 1 Environmental Signals and Normal Development CHAPTER 1 The Environment as a Normal Agent in Producing Phenotypes 3 CHAPTER 2 How Agents in the Environment Effect Molecular Changes in Development 37 CHAPTER 3 Developmental Symbiosis: Co-Development as a Strategy for Life 79 CHAPTER 4 Embryonic Defenses: Survival in a Hostile World 119 PART 2 Ecological Developmental Biology and Disease States CHAPTER 5 Teratogenesis: Environmental Assaults on Development 167 CHAPTER 6 Endocrine Disruptors 197 CHAPTER 7 The Epigenetic Origin of Adult Diseases 245 PART 3 Toward a Developmental Evolutionary Synthesis CHAPTER 8 The Modern Synthesis: Natural Selection of Allelic Variation 289 CHAPTER 9 Evolution through Developmental Regulatory Genes 323 CHAPTER 10 Environment, Development, and Evolution: Toward a New Synthesis 369 CODA Philosophical Concerns Raised by Ecological Developmental Biology 403 APPENDIX A Lysenko, Kammerer, and the Truncated Tradition of Ecological Developmental Biology 421 APPENDIX B The Molecular Mechanisms of Epigenetic Change 433 APPENDIX C Writing Development Out of the Modern Synthesis 441 APPENDIX D Epigenetic Inheritance Systems:
    [Show full text]
  • Early-Life Experience, Epigenetics, and the Developing Brain
    Neuropsychopharmacology REVIEWS (2015) 40, 141–153 & 2015 American College of Neuropsychopharmacology. All rights reserved 0893-133X/15 REVIEW ............................................................................................................................................................... www.neuropsychopharmacologyreviews.org 141 Early-Life Experience, Epigenetics, and the Developing Brain 1 ,1 Marija Kundakovic and Frances A Champagne* 1Department of Psychology, Columbia University, New York, NY, USA Development is a dynamic process that involves interplay between genes and the environment. In mammals, the quality of the postnatal environment is shaped by parent–offspring interactions that promote growth and survival and can lead to divergent developmental trajectories with implications for later-life neurobiological and behavioral characteristics. Emerging evidence suggests that epigenetic factors (ie, DNA methylation, posttranslational histone modifications, and small non- coding RNAs) may have a critical role in these parental care effects. Although this evidence is drawn primarily from rodent studies, there is increasing support for these effects in humans. Through these molecular mechanisms, variation in risk of psychopathology may emerge, particularly as a consequence of early-life neglect and abuse. Here we will highlight evidence of dynamic epigenetic changes in the developing brain in response to variation in the quality of postnatal parent–offspring interactions. The recruitment of epigenetic pathways for the
    [Show full text]
  • Zinc Fingers and a Green Thumb: Manipulating Gene Expression in Plants Segal, Stege and Barbas 165
    163 Zinc fingers and a green thumb: manipulating gene expression in plants David J Segaly, Justin T Stegez and Carlos F Barbas IIIç Artificial transcription factors can be rapidly constructed A variety of techniques have been developed to manip- from predefined zinc-finger modules to regulate virtually any ulate gene expression in plants. Increased expression of gene. Stable, heritable up- and downregulation of endogenous genes is most commonly achieved through endogenous genes has been demonstrated in transgenic transgene overexpression [1]. The introduction of tissue- plants. These advances promise new approaches for creating specific and inducible promoters has improved the utility functional knockouts and conditional overexpression, and of this approach, and efficient and robust plant transforma- for other gene discovery and manipulation applications in tion techniques have made the construction of transgenes plants. a relatively routine task. However, variable expression and co-suppression of transgenes often complicate this process. Addresses Furthermore, transgenes cannot accommodate alternative ÃThe Skaggs Institute for Chemical Biology and the Department of splicing, which may be important for the appropriate Molecular Biology, The Scripps Research Institute, La Jolla, function of some transgenes [2]. California 92037, USA yDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona 85721, USA Reducing or eliminating the expression of a gene in plants zDiversa Corporation, San Diego, California 92121, USA is not as simple as overexpressing a gene. Gene disruption §The Scripps Research Institute, BCC-550, North Torrey Pines Road, by homologous recombination, tDNA insertions and che- La Jolla, California 92037, USA mical mutagenesis has been used successfully, but these e-mail: [email protected] Correspondence: Carlos F Barbas III approaches are inefficient and time-consuming technolo- gies.
    [Show full text]
  • Genetics, Epigenetics and Disease a Literature Review By: Anthony M
    Genetics, Epigenetics and Disease A Literature Review By: Anthony M. Pasek Faculty Advisor: Rodger Tepe, PhD A senior research project submitted in partial requirement for the degree Doctor of Chiropractic August 11, 2011 Abstract Objective – This article provides an overview of the scientific literature available on the subject of genetic mechanisms of disease etiology as compared to epigenetic mechanisms of disease etiology. The effects of environmental influences on genetic expression and transgenerational inheritance will also be examined. Methods – Searches of the keywords listed below in the databases PubMed and EBSCO Host yielded referenced articles from indexed journals, literature reviews, pilot studies, longitudinal studies, and conference meeting reports. Conclusion – Although current research trends indicate a relationship between the static genome and the dynamic environment and offer epigenetics as a mechanism, further research is necessary. Epigenetic processes have been implicated in many diseases including diabetes mellitus, obesity, cardiovascular disease, metabolic disease, cancer, autism, Alzheimer’s disease, depression, and addiction. Keywords – genetics, central dogma of biology, genotype, phenotype, genomic imprinting, epigenetics, histone modification, DNA methylation, agouti mice, epigenetic drift, Överkalix, Avon Longitudinal Study of Parents and Children (ALSPAC). 2 Introduction Genetics has long been the central field of biology and it’s central dogma states that DNA leads to RNA, which leads to protein and ultimately determines human health or sickness1. The Human Genome Project marked a great triumph for humanity and researchers expected to solve the riddle of many complex diseases with the knowledge gleamed from this project. However, many more questions were raised than answered. Several rare genetic disorders including hemophilia and cystic fibrosis were explained by alterations in the genetic code but true genetic diseases only affect about one percent of the human population2.
    [Show full text]
  • Botany Genetics Mendelian Inheritance
    References 1. Elrod S., Stansfield W., 2002, Genetics, 4th Edition, Tata McGraw-Hill 2. Strickberger M. W., 1985, Genetics, 3rd Edition, Macmillan Publishing Company 3. Griffiths A. J., Wessler S.R., Lewontin R.C., Carrol S. B., 2008, Introduction to Genetic Analysis, 9th Edition, W. H. Freeman and Company 4. Klug W.S., Cumming M.R., Spencer C. A., Palladino M. A., 2009, Concepts of Genetics, 9th Edition, Benjamin Cummings Publication 5. Tamarin R. H., 2002, Principles of Genetics, 7th Edition, Tata McGraw-Hill 6. Hartwell L.H., Hood L., Goldberg M.L., Reynolds A.E., Silver L. M., Veres R. C., 2004, Genetics, 2nd Edition, McGraw-Hill 7. Pierce B.A., Genetics: A Conceptual Approach, 4th edition, W.H. Freeman 8. T.H. Noel Ellis, Julie M.I. Hofer, Gail M. Timmerman-Vaughan, Clarice J. Coyne and Roger P. Hellens, 2011, Mendel, 150 years on, Trends in Plant Science, Vol. 16, 590-596 Genetics Botany Mendelian Inheritance Learn More / Supporting Materials / Source of Further Reading 2.1 Glossary Starting Term Defination Related Term Character <Character> < Genotype > < Genotype of an organism is the gene combination it possesses. Genotype of phenotypically yellow seeded F1 may be YY or Yy.> <Character> < Phenotype > < Phenotype refers to the observable attributes of an organism. Plants with either of the two genotypes Yy or Yy are phenotypically yellow seeded.> <Character> < Homozygote > < A plant with a pair of identical alleles is called as Homozygote (Y/Y or y/y).> <Character> < Heterozygote > < a plant in which the <term2> allele of the pair differ is called as heterozygote (Y/y).> <Character> < locus > < A locus (plural: loci) is the location of a gene on a chromosome.
    [Show full text]
  • From 1957 to Nowadays: a Brief History of Epigenetics
    International Journal of Molecular Sciences Review From 1957 to Nowadays: A Brief History of Epigenetics Paul Peixoto 1,2, Pierre-François Cartron 3,4,5,6,7,8, Aurélien A. Serandour 3,4,6,7,8 and Eric Hervouet 1,2,9,* 1 Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000 Besançon, France; [email protected] 2 EPIGENEXP Platform, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France 3 CRCINA, INSERM, Université de Nantes, 44000 Nantes, France; [email protected] (P.-F.C.); [email protected] (A.A.S.) 4 Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l’Ouest, 44805 Saint Herblain, France 5 Cancéropole Grand-Ouest, Réseau Niches et Epigénétique des Tumeurs (NET), 44000 Nantes, France 6 EpiSAVMEN Network (Région Pays de la Loire), 44000 Nantes, France 7 LabEX IGO, Université de Nantes, 44000 Nantes, France 8 Ecole Centrale Nantes, 44300 Nantes, France 9 DImaCell Platform, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France * Correspondence: [email protected] Received: 9 September 2020; Accepted: 13 October 2020; Published: 14 October 2020 Abstract: Due to the spectacular number of studies focusing on epigenetics in the last few decades, and particularly for the last few years, the availability of a chronology of epigenetics appears essential. Indeed, our review places epigenetic events and the identification of the main epigenetic writers, readers and erasers on a historic scale. This review helps to understand the increasing knowledge in molecular and cellular biology, the development of new biochemical techniques and advances in epigenetics and, more importantly, the roles played by epigenetics in many physiological and pathological situations.
    [Show full text]
  • Epigenetics Analysis and Integrated Analysis of Multiomics Data, Including Epigenetic Data, Using Artificial Intelligence in the Era of Precision Medicine
    biomolecules Review Epigenetics Analysis and Integrated Analysis of Multiomics Data, Including Epigenetic Data, Using Artificial Intelligence in the Era of Precision Medicine Ryuji Hamamoto 1,2,*, Masaaki Komatsu 1,2, Ken Takasawa 1,2 , Ken Asada 1,2 and Syuzo Kaneko 1 1 Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; [email protected] (M.K.); [email protected] (K.T.); [email protected] (K.A.); [email protected] (S.K.) 2 Cancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan * Correspondence: [email protected]; Tel.: +81-3-3547-5271 Received: 1 December 2019; Accepted: 27 December 2019; Published: 30 December 2019 Abstract: To clarify the mechanisms of diseases, such as cancer, studies analyzing genetic mutations have been actively conducted for a long time, and a large number of achievements have already been reported. Indeed, genomic medicine is considered the core discipline of precision medicine, and currently, the clinical application of cutting-edge genomic medicine aimed at improving the prevention, diagnosis and treatment of a wide range of diseases is promoted. However, although the Human Genome Project was completed in 2003 and large-scale genetic analyses have since been accomplished worldwide with the development of next-generation sequencing (NGS), explaining the mechanism of disease onset only using genetic variation has been recognized as difficult. Meanwhile, the importance of epigenetics, which describes inheritance by mechanisms other than the genomic DNA sequence, has recently attracted attention, and, in particular, many studies have reported the involvement of epigenetic deregulation in human cancer.
    [Show full text]
  • Epigenetics: the Biochemistry of DNA Beyond the Central Dogma
    Epigenetics: The Biochemistry of DNA Beyond the Central Dogma Since the Human Genome Project was completed, the newly emerging field of epigenetics is providing a basis for understanding how heritable changes, other than those in the DNA sequence, can influence phenotypic variation. Epigenetics, essentially, affects how genes are read by cells and subsequently how they produce proteins. The interest in epigenetics has led to new findings about the relationship between epigenetic changes and a host of disorders including cancer, immune disorders, and neuropsychiatric disorders. The field of epigenetics is quickly growing and with it the understanding that both the environment and lifestyle choices can directly interact with the genome to influence epigenetic change. This unit is designed to provide a detailed look at the influence of epigenetics on gene expression through developmental stages, tissue-specific needs, and environmental impacts. Students will complete this unit with the understanding that gene regulation and expression is truly “above the genome” and well beyond the simplified mechanism of the Central Dogma of Biology. University of Florida Center for Precollegiate Education and Training www.cpet.ufl.edu 1 EPIGENETICS: THE BIOCHEMISTRY OF DNA www.cpet.ufl.edu 2 Author: Susan Chabot This curriculum was developed as part of Biomedical Explorations: Bench to Bedside, which is supported by the Office Of The Director, National Institutes Of Health of the National Institutes of Health under Award Number R25 OD016551. The content
    [Show full text]
  • 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.
    [Show full text]
  • Chapter 12 Gene Expression and Regulation
    PYF12 3/21/05 8:04 PM Page 191 Chapter 12 Gene expression and regulation Bacterial genomes usually contain several thousand different genes. Some of the gene products are required by the cell under all growth conditions and are called house- keeping genes. These include the genes that encode such proteins as DNA poly- merase, RNA polymerase, and DNA gyrase. Many other gene products are required under specific growth conditions. These include enzymes that synthesize amino acids, break down specific sugars, or respond to a specific environmental condition such as DNA damage. Housekeeping genes must be expressed at some level all of the time. Frequently, as the cell grows faster, more of the housekeeping gene products are needed. Even under very slow growth, some of each housekeeping gene product is made. The gene prod- ucts required for specific growth conditions are not needed all of the time. These genes are frequently expressed at extremely low levels, or not expressed at all when they are not needed and yet made when they are needed. This chapter will examine gene regulation or how bacteria regulate the expression of their genes so that the genes that are being expressed meet the needs of the cell for a specific growth condition. Gene regulation can occur at three possible places in the production of an active gene product. First, the transcription of the gene can be regulated. This is known as transcriptional regulation. When the gene is transcribed and how much it is transcribed influences the amount of gene product that is made. Second, if the gene encodes a protein, it can be regulated at the translational level.
    [Show full text]
  • 1 Genetics, Genomics and Cell Biology, Spring 2013 Instructors
    Genetics, Genomics and Cell Biology, Spring 2013 Monday, Wednesday, Friday 9-10 AM, 2050 VLSB Instructors Michael Levine, Ph.D. ([email protected]; office hours Friday 3-5 PM, 243 Dwinelle) Craig Miller, Ph.D. ([email protected]; office hours: Friday 3-5 PM, 243 Dwinelle) Rebecca Heald, Ph.D. ([email protected]; office hours: TBA) GSIs Jeremy Amon ([email protected]; office hours TBA) Peter Combs ([email protected]; office hours TBA) Anna Maria Desai ([email protected]; office hours TBA) Anna Park ([email protected]; office hours TBA) Jennifer Parks ([email protected]; office hours TBA) Course focus This course will introduce students to key concepts in genetic analysis, eukaryotic cell biology, and state-of-the-art approaches in genomics. Lectures will highlight basic knowledge of cellular processes that form the basis for human diseases. Prerequisite courses will have introduced students to the concepts of cells, the central dogma of molecular biology, and gene regulation. Emphasis in this course will be on eukaryotic cell processes, including cellular organization, dynamics and signaling. Grading Midterm 1 (Feb 21, 7:00-9:00 PM) 100 points Midterm 2 (Mar 14, 7:00-9:00 PM) 100 points Final exam (May 13, 7-10 PM) 200 points Quizzes (3 total, 25 points each) 75 points Mini Quizzes (10 total, 2.5 points each) 25 points Total 500 points Quizzes are given during discussion sections with weekly mini quizzes and one 25 point quiz during each third of the course. Your lowest mini quiz score will be dropped and your mini quiz total score will be based upon the remaining 9 mini quizzes.
    [Show full text]