Site Specific And Global Epigenomic Editing

In recent years, alongside the largely popularized advances in human genome editing and CRISPR-cas9-driven therapeutics, epigenomic editing has made strong strides, though a clear understanding is still forming in the field of the exact role that epigenetics play in pathogenesis, the full range of sites for possible epigenetic modification, and the potential to target these sites to modulate disease progression. Key questions for researchers embarking in this field include: Which of the hundreds of epigenomic marks and features are relevant, and which of those are likely to serve a role in regulating gene expression, cell behavior, and phenotypic outcomes? This volume is the first to provide a thorough, conceptual introduction to the field of epigenetic regulation and a thorough accounting of sites for possible epigenetic edits and disease modulation. Protocols, and applied case studies examine early disease targets and likely pathways of therapeutic significance, while also outlining common challenges in the field, and the addressing the range of bioethical questions that come with altering phenotypes. This book addresses its topic in a comprehensive, but accessible manner, highlighting practical tools and burning questions remaining in the field to enable fresh research. Offers a full, conceptual and applied framework for implementing epigenomic editing in biological research and drug discovery Discusses fundamental theory, experimental design, and applied approaches alongside common research challenges and bioethical concerns Examines epigenomic editing's potential role in modulation of developmental, neuropsychiatric, and immunological disorders, as well as viral infections and cancer

Many inheritable changes in gene function are not explained by changes in the DNA sequence. Such epigenetic mechanisms are known to influence gene function in most complex organisms and include effects such as transposon function, chromosome imprinting, yeast mating type switching and telomeric silencing. In recent years, epigenetic effects have become a major focus of research activity. This monograph, edited by three well-known biologists from different specialties, is the first to review and synthesize what is known about these effects across all species, particularly from a molecular perspective, and will be of interest to everyone in the fields of molecular biology and genetics.

This book serves as an introduction to targeted genome editing, beginning with the background of this rapidly developing field and methods for generation of engineered nucleases. Applications of genome editing tools are then described in detail, in iPS cells and diverse organisms such as mice, rats, marine invertebrates, fish, frogs, and plants. Tools that are mentioned include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9, all of which have received much attention in recent years as breakthrough technologies. Genome editing with engineered nucleases allows us to precisely change the target genome of living cells and is a powerful way to control functional genes. It is feasible in almost all organisms ranging from bacteria to plants and animals, as well as in cultured cells such as ES and iPS cells. Various genome modifications have proven successful, including gene knockout and knock-in experiments with targeting vectors and chromosomal editing. Genome editing technologies hold great promise for the future, for example in biomedical research, clinical medicine, and generation of crops and livestock with desirable traits. A wide range of readers will find this book interesting, and with its focus on applications in a variety of organisms and cells, the book will be valuable for life scientists in all fields.

Epigenetics is the study of both heritable and non-heritable changes in the regulation of gene activity and expression that occur without an alteration in the DNA sequence. This dynamic and rapidly developing discipline is making its impact across the biomedical sciences, in particular in toxicology where epigenetic differences can mean that different individuals respond differently to the same drug or chemical. Toxicology and Epigenetics reflects the multidimensional character of this emerging area of toxicology, describing cutting-edge molecular technologies to unravel epigenetic changes, the use of in vivo and in vitro models, as well as the potential use of toxicological epigenetics in regulatory environments. An international team of experts consider the interplay between epigenetics and toxicology in a number of areas, including environmental, nutritional, pharmacological, and computational toxicology, nanomaterials, proteomics and metabolomics, and cancer research. Topics covered include: environment, epigenetics and diseases DNA methylation and toxicogenomics chromatin at the intersection of disease and therapy epigenomic actions of environmental arsenicals environment, epigenetics and cardiovascular health toxicology, epigenetics and autoimmunity ocular epigenomics: potential sites of environmental impact in development and disease nuclear RNA silencing and related phenomena in animals epigenomics – impact for drug safety sciences methods of global epigenomic profiling transcriptomics: applications in epigenetic toxicology Toxicology and Epigenetics is an essential insight into the current trends and future directions of research in this rapidly expanding field for investigators, toxicologists, risk assessors and regulators in academia, industry and government.

This detailed book explores the concepts and applications of epigenome editing, as presented by leading scientists in the field. Beginning with some general and topical reviews, the collection continues by covering the design of DNA-binding devices, optimization of the effector domains, readout of epigenome marks, and approaches for delivery at the cellular and organismal level. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Epigenome Editing: Methods and Protocols will be of great assistance to people new to the field but also to those already engaged, as epigenetic editing is still a relatively unexplored field with many issues to be resolved.

Heritable human genome editing - making changes to the genetic material of eggs, sperm, or any cells that lead to their development, including the cells of early embryos, and establishing a pregnancy - raises not only scientific and medical considerations but also a host of ethical, moral, and societal issues. Human embryos whose genomes have been edited should not be used to create a pregnancy until it is established that precise genomic changes can be made reliably and without introducing undesired changes - criteria that have not yet been met, says Heritable Human Genome Editing. From an international commission of the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the U.K.'s Royal Society, the report considers potential benefits, harms, and uncertainties associated with genome editing technologies and defines a translational pathway from rigorous preclinical research to initial clinical uses, should a country decide to permit such uses. The report specifies stringent preclinical and clinical requirements for establishing safety and efficacy, and for undertaking long-term monitoring of outcomes. Extensive national and international dialogue is needed before any country decides whether to permit clinical use of this technology, according to the report, which identifies essential elements of national and international scientific governance and oversight.

In recent years, the field of epigenetics has grown significantly, driving new understanding of human developmental processes and disease expression, as well as advances in diagnostics and therapeutics. As the field of epigenetics continues to grow, methods and technologies have multiplied, resulting in a wide range of approaches and tools researchers might employ. Epigenetics Methods offers comprehensive instruction in methods, protocols, and experimental approaches applied in field of epigenetics. Here, across thirty-five chapters, specialists offer step-by-step overviews of methods used to study various epigenetic mechanisms, as employed in basic and translational research. Leading the reader from fundamental to more advanced methods, the book begins with thorough instruction in DNA methylation techniques and gene or locus-specific methylation analyses, followed by histone modification methods, chromatin evaluation, enzyme analyses of histone methylation, and studies of non-coding RNAs as epigenetic modulators. Recently developed techniques and technologies discussed include single-cell epigenomics, epigenetic editing, computational epigenetics, systems biology epigenetic methods, and forensic epigenetic approaches. Epigenetics methods currently in-development, and their implication for future research, are also considered in-depth. In addition, as with the wider life sciences, reproducibility across experiments, labs, and subdisciplines is a growing issue for epigenetics researchers. This volume provides consensus-driven methods instruction and overviews. Tollefsbol and contributing authors survey the range of existing methods; identify best practices, common themes, and challenges; and bring unity of approach to a diverse and ever-evolving field. Includes contributions by leading international investigators involved in epigenetic research and clinical and therapeutic application Integrates technology and translation with fundamental chapters on epigenetics methods, as well as chapters on more novel and advanced epigenetics methods Written at verbal and technical levels that can be understood by scientists and students alike Includes chapters on state-of-the-art techniques such as single-cell epigenomics, use of CRISPR/Cas9 for epigenetic editing, and epigenetics methods applied to forensics

Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors play a role in gene expression. The goal of this volume is to highlight those diseases or conditions for which we have advanced knowledge of epigenetic factors such as cancer, autoimmune disorders and aging as well as those that are yielding exciting breakthroughs in epigenetics such as diabetes, neurobiological disorders and cardiovascular disease. Where applicable, attempts are made to not only detail the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, but also novel epigenetic approaches to the treatment of these diseases. Chapters are also presented on human imprinting disorders, respiratory diseases, infectious diseases and gynecological and reproductive diseases. Since epigenetics plays a major role in the aging process, advances in the epigenetics of aging are highly relevant to many age-related human diseases. Therefore, this volume closes with chapters on aging epigenetics and breakthroughs that have been made to delay the aging process through epigenetic approaches. With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike. Comprehensive coverage of fundamental and emergent science and clinical usage Side-by-side coverage of the basis of epigenetic diseases and their treatments Evaluation of recent epigenetic clinical breakthroughs