Histone Recognition
Histone Recognition

Author: Ming-Ming Zhou

Publisher: Springer

Published: 2015-05-29

Total Pages: 284

ISBN-13: 3319181025

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This book provides a timely review of the role of histone modifications in epigenetic control of gene expression. Topics covered include: basic mechanisms of molecular recognition of histone post-translational modification (PTMs); combinatorial readout of histone PTMs by tandem epigenome reader domains; genome-wide profiling of histone PTM interactions; small molecule modulation of histone PTM interactions and their potential as a new approach to therapeutic intervention in human diseases. All chapters were written by leading scientists who made the original key discoveries of the structure and mechanism of evolutionarily conserved reader domains, which serve to direct gene transcription in chromatin through interactions with DNA-packing histones in a PTM-sensitive manner.

Regulation of Alternative Splicing
Regulation of Alternative Splicing

Author: Philippe Jeanteur

Publisher: Springer Science & Business Media

Published: 2002-10-21

Total Pages: 272

ISBN-13: 9783540438335

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The discovery in 1977 that genes are split into exons and introns has done away with the one gene - one protein dogma. Indeed, the removal of introns from the primary RNA transcript is not necessarily straightforward since there may be optional pathways leading to different messenger RNAs and consequently to different proteins. Examples of such an alternative splicing mechanism cover all fields of biology. Moreover, there are plenty of occurrences where deviant splicing can have pathological effects. Despite the high number of specific cases of alternative splicing, it was not until recently that the generality and extent of this phenomenon was fully appreciated. A superficial reading of the preliminary sequence of the human genome published in 2001 led to the surprising, and even deceiving to many scientists, low number of genes (around 32,000) which contrasted with the much higher figure around 150,000 which was previously envisioned. Attempts to make a global assessment of the use of alternative splicing are recent and rely essentially on the comparison of genomic mRNA and EST sequences as reviewed by Thanaraj and Stamm in the first chapter of this volume. Most recent estimates suggest that 40-60% of human genes might be alternatively spliced, as opposed to about 22% for C. elegans.

The DNA, RNA, and Histone Methylomes
The DNA, RNA, and Histone Methylomes

Author: Stefan Jurga

Publisher: Springer Nature

Published: 2019-08-28

Total Pages: 624

ISBN-13: 3030147924

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This book reviews the chemical, regulatory, and physiological mechanisms of protein arginine and lysine methyltransferases, as well as nucleic acid methylations and methylating enzymes. Protein and nucleic acid methylation play key and diverse roles in cellular signalling and regulating macromolecular cell functions. Protein arginine and lysine methyltransferases are the predominant enzymes that catalyse S-adenosylmethionine (SAM)-dependent methylation of protein substrates. These enzymes catalyse a nucleophilic substitution of a methyl group to an arginine or lysine side chain nitrogen (N) atom. Cells also have additional protein methyltransferases, which target other amino acids in peptidyl side chains or N-termini and C-termini, such as glutamate, glutamine, and histidine. All these protein methyltransferases use a similar mechanism. In contrast, nucleic acids (DNA and RNA) are substrates for methylating enzymes, which employ various chemical mechanisms to methylate nucleosides at nitrogen (N), oxygen (O), and carbon (C) atoms. This book illustrates how, thanks to there ability to expand their repertoire of functions to the modified substrates, protein and nucleic acid methylation processes play a key role in cells.

Chromatin Signaling and Diseases
Chromatin Signaling and Diseases

Author: Olivier Binda

Publisher: Academic Press

Published: 2016-08-06

Total Pages: 468

ISBN-13: 012802609X

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Chromatin Signaling and Diseases covers the molecular mechanisms that regulate gene expression, which govern everything from embryonic development, growth, and human pathologies associated with aging, such as cancer. This book helps researchers learn about or keep up with the quickly expanding field of chromatin signaling. After reading this book, clinicians will be more capable of explaining the mechanisms of gene expression regulation to their patients to reassure them about new drug developments that target chromatin signaling mechanisms. For example, several epigenetic drugs that act on chromatin signaling factors are in clinical trials or even approved for usage in cancer treatments, Alzheimer's, and Huntington's diseases. Other epigenetic drugs are in development to regulate various class of chromatin signaling factors. To keep up with this changing landscape, clinicians and doctors will need to stay familiar with genetic advances that translate to clinical practice, such as chromatin signaling. Although sequencing of the human genome was completed over a decade ago and its structure investigated for nearly half a century, molecular mechanisms that regulate gene expression remain largely misunderstood. An emerging concept called chromatin signaling proposes that small protein domains recognize chemical modifications on the genome scaffolding histone proteins, facilitating the nucleation of enzymatic complexes at specific loci that then open up or shut down the access to genetic information, thereby regulating gene expression. The addition and removal of chemical modifications on histones, as well as the proteins that specifically recognize these, is reviewed in Chromatin Signaling and Diseases. Finally, the impact of gene expression defects associated with malfunctioning chromatin signaling is also explored. - Explains molecular mechanisms that regulate gene expression, which governs everything from embryonic development, growth, and human pathologies associated with aging - Educates clinicians and researchers about chromatin signaling, a molecular mechanism that is changing our understanding of human pathology - Explores the addition and removal of chemical modifications on histones, the proteins that specifically recognize these, and the impact of gene expression defects associated with malfunctioning chromatin signaling - Helps researchers learn about the quickly expanding field of chromatin signaling

Role of DNA Methyltransferases in the Epigenome
Role of DNA Methyltransferases in the Epigenome

Author: Albert Jeltsch

Publisher: MDPI

Published: 2020-03-05

Total Pages: 150

ISBN-13: 3039280201

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DNA methylation, a modification found in most species, regulates chromatin functions in conjunction with other epigenome modifications, such as histone post-translational modifications and non-coding RNAs. In mammals, DNA methylation has an essential role in development by orchestrating the generation and maintenance of the phenotypic diversity of human cell types. Recent years have brought spectacular advances in our understanding of the mechanism, function and regulation of DNA methyltransferases through their interaction with other epigenome modifications, chromatin factors and post-translational modifications, which are described in this Special Issue of Genes. Manuscripts are specifically addressing describing the targeting and regulation of DNA methyltransferases by interacting factors and their roles in cellular differentiation and the development of diseases. Prof. Dr. Albert Jeltsch and Prof. Dr. Humaira Gowher, Guest Editors

Comprehensive Toxicology
Comprehensive Toxicology

Author:

Publisher: Elsevier

Published: 2017-12-01

Total Pages: 8639

ISBN-13: 0081006128

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Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system Features additional coverage throughout and a new volume on toxicology of the hematopoietic system Presents in-depth, comprehensive coverage from an international author base of domain experts

Epigenetics in Human Disease
Epigenetics in Human Disease

Author: Trygve O Tollefsbol

Publisher: Academic Press

Published: 2018-05-18

Total Pages: 1112

ISBN-13: 012812329X

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Epigenetics in Human Disease, Second Edition examines the diseases and conditions on which we have advanced knowledge of epigenetic mechanisms, such as cancer, autoimmune disorders, aging, metabolic disorders, neurobiological disorders and cardiovascular disease. In addition to detailing the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, novel epigenetic approaches to treatment are also explored. Fully revised and up-to-date, this new edition discusses topics of current interest in epigenetic research, including stem cell epigenetic therapy, bioinformatic analysis of NGS data, and epigenetic mechanisms of imprinting disorders. Further sections explore online epigenetic tools and datasets, early-life programming of epigenetics in age-related diseases, the epigenetics of addiction and suicide, and epigenetic approaches to regulating and preventing diabetes, cardiac disease, allergic disorders, Alzheimer's disease, respiratory diseases, and many other human maladies. - Includes contributions from leading international investigators involved in translational epigenetic research and therapeutic applications - Integrates methods and applications with fundamental chapters on epigenetics in human disease, along with an evaluation of recent clinical breakthroughs - Presents side-by-side coverage of the basis of epigenetic diseases and treatment pathways - Provides a fully revised resource covering current developments, including stem cell epigenetic therapy, the bioinformatic analysis of NGS data, epigenetic mechanisms of imprinting disorders, online epigenetic tools and datasets, and more

Fundamentals of Chromatin
Fundamentals of Chromatin

Author: Jerry L. Workman

Publisher: Springer Science & Business Media

Published: 2013-12-04

Total Pages: 594

ISBN-13: 1461486246

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​​​​​​​​​​​​​While there has been an increasing number of books on various aspects of epigenetics, there has been a gap over the years in books that provide a comprehensive understanding of the fundamentals of chromatin. ​Chromatin is the combination of DNA and proteins that make up the genetic material of chromosomes. Its primary function is to package DNA to fit into the cell, to strengthen the DNA to prevent damage, to allow mitosis and meiosis, and to control the expression of genes and DNA replication. The audience for this book is mainly newly established scientists ​and graduate students. Rather than going into the more specific areas of recent research on chromatin the chapters in this book give a strong, updated groundwork about the topic. Some the fundamentals that this book will cover include the structure of chromatin and biochemistry and the enzyme complexes that manage it.

Structural Biology in Drug Discovery
Structural Biology in Drug Discovery

Author: Jean-Paul Renaud

Publisher: John Wiley & Sons

Published: 2020-01-27

Total Pages: 692

ISBN-13: 1118900405

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With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins