Download or read book Site Specific and Global Epigenomic Editing written by Feng C Zhou and published by Academic Press. This book was released on 2022-06-15 with total page 704 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Epigenome Editing written by Albert Jeltsch and published by Springer Nature. This book was released on with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Targeted Genome Editing Using Site Specific Nucleases written by Takashi Yamamoto and published by Springer. This book was released on 2015-01-05 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Epigenetic Mechanisms of Gene Regulation written by Vincenzo E. A. Russo and published by . This book was released on 1996 with total page 716 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Epigenetics Methods written by Trygve Tollefsbol and published by Academic Press. This book was released on 2020-07-08 with total page 736 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Epigenetic Gene Expression and Regulation written by Suming Huang and published by Academic Press. This book was released on 2015-10-19 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Gene Expression and Regulation reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies. The book shows how these heritable mechanisms allow individual cells to establish stable and unique patterns of gene expression that can be passed through cell divisions without DNA mutations, thereby establishing how different heritable patterns of gene regulation control cell differentiation and organogenesis, resulting in a distinct human organism with a variety of differing cellular functions and tissues. The work begins with basic biology, encompasses methods, cellular and tissue organization, topical issues in epigenetic evolution and environmental epigenesis, and lastly clinical disease discovery and treatment. Each highly illustrated chapter is organized to briefly summarize current research, provide appropriate pedagogical guidance, pertinent methods, relevant model organisms, and clinical examples. Reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies Helps readers understand how epigenetic marks are targeted, and to what extent transgenerational epigenetic changes are instilled and possibly passed onto offspring Chapters are replete with clinical examples to empower the basic biology with translational significance Offers more than 100 illustrations to distill key concepts and decipher complex science

Download or read book Epigenetic Therapy of Cancer written by Michael Lübbert and published by Springer Science & Business Media. This book was released on 2013-12-12 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.

Download or read book Epigenetic Technological Applications written by Yujun George Zheng and published by Academic Press. This book was released on 2015-05-30 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Technological Applications is a compilation of state-of-the-art technologies involved in epigenetic research. Epigenetics is an exciting new field of biology research, and many technologies are invented and developed specifically for epigenetics study. With chapters covering the latest developments in crystallography, computational modeling, the uses of histones, and more, Epigenetic Technological Applications addresses the question of how these new ideas, procedures, and innovations can be applied to current epigenetics research, and how they can keep pushing discovery forward and beyond the epigenetic realm. Discusses technologies that are critical for epigenetic research and application Includes epigenetic applications for state-of-the-art technologies Contains a global perspective on the future of epigenetics

Download or read book Heritable Human Genome Editing written by The Royal Society and published by National Academies Press. This book was released on 2021-01-16 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Epigenetic Biomarkers and Diagnostics written by Jose Luis Garcia-Gimenez and published by Academic Press. This book was released on 2015-12-07 with total page 698 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Biomarkers and Diagnostics comprises 31 chapters contributed by leading active researchers in basic and clinical epigenetics. The book begins with the basis of epigenetic mechanisms and descriptions of epigenetic biomarkers that can be used in clinical diagnostics and prognostics. It goes on to discuss classical methods and next generation sequencing-based technologies to discover and analyze epigenetic biomarkers. The book concludes with an account of DNA methylation, post-translational modifications and noncoding RNAs as the most promising biomarkers for cancer (i.e. breast, lung, colon, etc.), metabolic disorders (i.e. diabetes and obesity), autoimmune diseases, infertility, allergy, infectious diseases, and neurological disorders. The book describes the challenging aspects of research in epigenetics, and current findings regarding new epigenetic elements and modifiers, providing guidance for researchers interested in the most advanced technologies and tested biomarkers to be used in the clinical diagnosis or prognosis of disease. Focuses on recent progress in several areas of epigenetics, general concepts regarding epigenetics, and the future prospects of this discipline in clinical diagnostics and prognostics Describes the importance of the quality of samples and clinical associated data, and also the ethical issues for epigenetic diagnostics Discusses the advances in epigenomics technologies, including next-generation sequencing based tools and applications Expounds on the utility of epigenetic biomarkers for diagnosis and prognosis of several diseases, highlighting the study of these biomarkers in cancer, cardiovascular and metabolic diseases, infertility, and infectious diseases Includes a special section that discusses the relevance of biobanks in the maintenance of high quality biosamples and clinical-associated data, and the relevance of the ethical aspects in epigenetic studies

Download or read book Designing Epigenome Editing Tools to Understand the Functional Role of DNA Methylation Changes in Cancer written by James McDonald (Molecular geneticist) and published by . This book was released on 2017 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA methylation is known to silence gene expression in the context of imprinting, X-chromosome inactivation, and retrotransposon silencing. However, the role of DNA methylation in silencing gene expression outside of these contexts is not fully understood. This is especially true in diseases such as cancer, where normal DNA methylation patterns are significantly altered. In breast cancer as well as nearly all cancer types, most of the genome loses DNA methylation while small regions of the genome gain methylation. DNA methylation generally correlates with decreased gene expression when present at a gene promoter. Therefore, these regions of hypo- and hyper-methylation may contribute to cancer development and progression by activating oncogenes or silencing tumor suppressor genes. My work focuses on building tools to study the functional role of DNA methylation changes and exploring how methylation changes at a gene promoter promote resistance to treatment in breast cancer.About 75% of breast cancers depend on estrogen signaling through the estrogen receptor (ER[alpha]). These tumors are effectively treated by aromatase inhibitors (AI) that prevent estrogen production. However, almost all advanced cases of ER[alpha] positive breast cancer develop resistance to AI therapy. I therefore sought to identify methylation changes that promote this resistance. I studied UCA1 and PTGER4, two genes identified by a screen for negatively correlated methylation and expression changes in a cell line model of AI resistance. UCA1 is a long non-coding RNA that promotes growth and metastasis in bladder cancer. PTGER4 encodes the prostaglandin E2 receptor 4 (EP4), which supports the progression of multiple cancer types by altering cell signaling. While my experiments did not indicate that UCA1 has a strong role in AI resistance, I found that hypomethylation of the PTGER4 promoter correlates with increased expression and EP4 signaling. My data further suggest that the downstream effector of EP4 signaling, CARM1, promotes endocrine therapy resistance by increasing the ligand-independent transcription activity of ER[alpha].The effects of local DNA methylation changes are most often identified by correlating the methylation and expression levels from two samples. To show that methylation causes the expression change, these studies rely on non-specific tools that demethylate the whole genome: DNA methyltransferase (DNMT) inhibitors or by DNMT knockout/knockdown. To build a tool capable of inducing site-specific DNA methylation changes, I fused the human DNMT3A catalytic domain to the RNA-guided nuclease Cas9 (the Cas9 is nuclease dead). I used this tool to induce up to 53% DNA methylation on individual cytosines within 50 bp of the target site. When multiple sites within the CDKN2A or ARF promoters were targeted, the induced DNA methylation decreased the expression of the targeted gene. To determine the optimal DNMT catalytic domain to use in this system, I created alternative DNMT fusions that included human DNMT1, a fusion of mouse Dnmt3a to mouse Dnmt3L, human DNMT3B, and the bacterial methyltransferase M.SssI. While the Dnmt3a-Dnmt3L fusion increased methylation relative to DNMT3A alone, it also induced more off-target methylation. The continued development of targeted DNA methylation technologies will increase our ability to identify functional methylation changes in tumors. As a result, we will learn the specific ways that methylation-induced gene expression changes contribute to cancer.

Download or read book Epigenetics in Human Disease written by Trygve Tollefsbol and published by Academic Press. This book was released on 2012-07-26 with total page 617 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Environmental Epigenetics written by L. Joseph Su and published by Springer. This book was released on 2015-05-18 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book examines the toxicological and health implications of environmental epigenetics and provides knowledge through an interdisciplinary approach. Included in this volume are chapters outlining various environmental risk factors such as phthalates and dietary components, life states such as pregnancy and ageing, hormonal and metabolic considerations and specific disease risks such as cancer cardiovascular diseases and other non-communicable diseases. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses.

Download or read book Human Genome Editing written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2017-08-13 with total page 329 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome editing is a powerful new tool for making precise alterations to an organism's genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions. Human Genome Editing considers important questions about the human application of genome editing including: balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. This report proposes criteria for heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents 7 general principles for the governance of human genome editing.

Download or read book Twin and Family Studies of Epigenetics written by Shuai Li and published by Academic Press. This book was released on 2021-08-19 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: Twin and Family Studies of Epigenetics, Volume 27, the latest release in the Translational Epigenetics series, gathers expert opinions on epigenetic twin and family study research methods, recent findings across various disease areas, and future directions. The book provides in-depth coverage of epigenetics fundamentals, twin and family epigenetic study design, and the broader role of epigenetics in answering questions on the developmental origins of health and disease. Throughout the volume, twin and family studies are employed to examine causes of epigenetic variation, the relationship between epigenetic modifications and mental illness, cancers, cardiovascular disease, diabetes, obesity, high blood pressure, and more. Emerging research methods applied in twin and family studies discussed include imaging epigenetics, exposure-specific DNA methylation changes, and unravelling time trends in epigenetic effects. Offers a practical, interdisciplinary approach across epigenetics, epidemiology and various disease specialties Applies epigenetic twin and family studies to determine the relationship between epigenetics and mental illness, cancers, cardiovascular disease, diabetes, obesity and high blood pressure, among other diseases and disorders Features chapter contributions from a wide range of international researchers in the field

Download or read book The Genetic Basis of Sleep and Sleep Disorders written by Paul Shaw and published by Cambridge University Press. This book was released on 2013-10-24 with total page 434 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first comprehensive book on the subject, The Genetic Basis of Sleep and Sleep Disorders covers detailed reviews of the general principles of genetics and genetic techniques in the study of sleep and sleep disorders. The book contains sections on the genetics of circadian rhythms, of normal sleep and wake states and of sleep homeostasis. There are also sections discussing the role of genetics in the understanding of insomnias, hypersomnias including narcolepsy, parasomnias and sleep-related movement disorders. The final chapter highlights the use of gene therapy in sleep disorders. Written by genetic experts and sleep specialists from around the world, the book is up to date and geared specifically to the needs of both researchers and clinicians with an interest in sleep medicine. This book will be an invaluable resource for sleep specialists, neurologists, geneticists, psychiatrists and psychologists.

Download or read book Mechanisms of DNA Methylation Control and Epigenome Engineering written by Wanlu Liu and published by . This book was released on 2018 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytosine DNA methylation is an evolutionarily conserved epigenetic mark that plays critical roles in diverse biological processes, including gene and transposon silencing and imprinting. In mammals, DNA methylation mostly occurs in the symmetric dinucleotide CG sites. In the model plant Arabidopsis thaliana, DNA methylation frequently occurs at cytosine bases in all sequence contexts (CG, CHG and CHH, where H represents A, C or T). In Arabidopsis, de novo DNA methylation is established by a process known as RNA-directed DNA methylation (RdDM). RdDM in plants not only requires the upstream production of 24-nucleotide (nt) small interfering RNAs (siRNAs) and the downstream recruitment of de novo DNA methyltransferase DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), the production of RNA polymerase V (Pol V)-dependent intergenic non-coding (IGN) transcripts plays a crucial role likely in serving as scaffolds for siRNAs binding. Pol V is required for DNA methylation and gene silencing and has been shown to be transcriptionally active in vitro. However, the characteristics of Pol V transcripts is poorly understood probably due to its low abundance. In this dissertation, to better understand the features of Pol V transcripts in vivo, I will first describe the application of a technique modified from global nuclear run-on (GRO) assay to characterize nascent Pol V transcripts at genome-wide level. With this technique, we captured Pol V nascent transcripts and we uncovered a novel mechanism of ARGONAUTE4/6/9 (AGO4/6/9) dependent, small-RNA-guided co-transcriptional slicing of nascent Pol V transcripts. With the fast development of genome editing recent years, epigenetic modification including targeted DNA methylation and demethylation also becomes attractive for its capability of stably regulate gene expression. In order to develop site-specific and efficient tools for DNA methylation targeting, we tethered artificial zinc finger protein recognizing specific DNA sequence to various RdDM proteins (ZF-RdDM) in Arabidopsis. With this tool, we studied the hierarchy of action within RdDM pathway by testing their ability to target methylation in different mutant backgrounds. Also, at thousands of ZF-RdDM off target sites, we characterized the ectopic siRNAs production, Pol V recruitment and DNA methylation establishment and found that simultaneously recruiting both arms of the RdDM pathway, siRNA biogenesis and Pol V recruitment, dramatically enhanced targeted methylation. We then also developed a tool to target DNA demethylation in plants by fusing the catalytic domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and an artificial zinc finger protein or CRISPR/dCas9 system. Finally, I will discuss DNA methylation landscape in human embryonic stem cells (hESCs). hESCs are morphologically and transcriptionally similar to stem cells derived from the mouse post-implantation epiblast. Thus, hESCs are typically considered to exhibit 'primed' pluripotency. Various culture conditions have been developed to promote maintenance and self-renewal of hypomethylated 'naive' hESCs. We have discovered that reverting primed hESCs to naive hESCs results in a Stage Specific Embryonic Antigen 4 (SSEA4)-negative population with a transcriptional program resembling the human pre-implantation epiblast. However, we also discovered that the methylation landscape of naive hESCs in vitro is distinct from human epiblast in vivo with a lost 'memory' of methylation state at primary imprints and human oocyte.