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Regulation of microRNAs

Regulation of microRNAs
  • Author : Helge Großhans
  • Publisher :Unknown
  • Release Date :2010-12-10
  • Total pages :160
  • ISBN : 1441978232
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Summary : Given this pervasiveness and importance of miRNA-mediated gene regulation, it should come as little surprise that miRNAs themselves are also highly regulated. However, the recent explosion of knowledge on this topic has been remarkable, providing a primary motivation for publication of this book. As miRNAs are transcribed by RNA polymerase II, the enzyme that also generates mRNAs, it was perhaps not unexpected that miRNA transcription would be subject to regulation, and we have willfully mitted this aspect from this monograph. However, what has been unexpected is the extent of post-transcriptional regulation of miRNAs that is illustrated in this book.

Epigenetic Gene Expression and Regulation

Epigenetic Gene Expression and Regulation
  • Author : Suming Huang,Michael D Litt,C. Ann Blakey
  • Publisher :Unknown
  • Release Date :2015-10-19
  • Total pages :482
  • ISBN : 9780128004715
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Summary : 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

Epigenetic Mechanisms in Cancer

Epigenetic Mechanisms in Cancer
  • Author : Sabita Saldanha
  • Publisher :Unknown
  • Release Date :2017-11-16
  • Total pages :392
  • ISBN : 9780128134603
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Summary : Epigenetic Mechanisms in Cancer provides a comprehensive analysis of epigenetic signatures that govern disease development, progression and metastasis. Epigenetic signatures dictating tumor etiologies present an opportunity for biomarker identification which has broad potential for improving diagnosis, prognosis, prediction, and risk assessment. This volumes offers a unique evaluation of signature differences in childhood, sex-specific and race-specific cancers, and in doing so broadly illuminates the scope of epigenetic biomarkers in clinical environments. Chapters detail the major epigenetic process in humans consisting of DNA methylation, histone modifications and microRNAs (miRNAs) involved in the initiation, progression and metastasis of tumors. Also delineated are recent technologies such as next generation sequencing that are used to identify epigenetic profiles (primarily methylation analysis) in samples (normal, benign and cancerous) and which are highly important to the analysis of epigenetic outcomes. Offers broad coverage that is applicable to audiences in various area of cancer research - population studies, diagnostics, prognosis, prediction, therapy, risk, etc. Provides critical review analysis of the topics that will clarify and delineate the potential roles of epigenetic signatures in cancer management Covers basic, as well as, clinical areas of epigenetic mechanisms in tumorigenesis Features contributions by leading experts in the field Provides comprehensive coverage of current epigenetic signatures involved in the etiology of various cancers and miRNAs

Essentials of Noncoding RNA in Neuroscience

Essentials of Noncoding RNA in Neuroscience
  • Author : Davide De Pietri Tonelli
  • Publisher :Unknown
  • Release Date :2017-06-14
  • Total pages :338
  • ISBN : 9780128498996
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Summary : Essentials of Noncoding RNA in Neuroscience: Ontogenetics, Plasticity of the Vertebrate Brain focuses on the role of miRNAs in neurogenesis, gliogenesis, neuronal network formation, and the cell biology of forebrain development. The important role miRNAs play in neuronal maturation, neocortex function, and in some neurodevelopmental disorders is discussed, as are the computational challenges and methods used in the identification of miRNA targets. This book is a valuable reference for neuroscientists who wish to better understand the role of miRNAs in complex processes. It is of strong interest to those working to develop enabling technologies to detect and monitor miRNA expression and function, and to evaluate its roles in neural progenitor proliferation/differentiation, neuronal plasticity, and learning and memory. Discusses the unique features of neural miRNAs Details functional investigation of miRNA actions and current experimental approaches Includes extensive coverage of miRNA biology, developmental and postnatal neurogenesis, and computational challenges for miRNA target identification Contains thorough discussion of the transcriptional control of miRNA expression in forebrain development and in specific neuronal subtypes, as well as miRNA function in neurogenesis, neuronal network maturation, plasticity, gliogenesis, and dysfunction Provides an overview of miRNA roles in neurodevelopmental disorders and their possible role in the evolution of the neocortex

Autophagy: Biology and Diseases

Autophagy: Biology and Diseases
  • Author : Zheng-Hong Qin
  • Publisher :Unknown
  • Release Date :2019-11-27
  • Total pages :727
  • ISBN : 9789811506024
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Summary : This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.

MicroRNA in Regenerative Medicine

MicroRNA in Regenerative Medicine
  • Author : Chandan K. Sen
  • Publisher :Unknown
  • Release Date :2014-11-26
  • Total pages :1288
  • ISBN : 9780124058583
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Summary : This work encapsulates the uses of miRNA across stem cells, developmental biology, tissue injury and tissue regeneration. In particular contributors provide focused coverage of methodologies, intervention and tissue engineering. Regulating virtually all biological processes, the genome’s 1048 encoded microRNAs appear to hold considerable promise for the potential repair and regeneration of tissues and organs in future therapies. In this work, 50 experts address key topics of this fast-emerging field. Concisely summarizing and evaluating key findings emerging from fundamental research into translational application, they point to the current and future significance of clinical research in the miRNA area. Coverage encompasses all major aspects of fundamental stem cell and developmental biology, including the uses of miRNA across repair and regeneration, and special coverage of methodologies and interventions as they point towards organ and tissue engineering Multi-colour text layout with 150 colour figures to illustrate important findings Take home messages encapsulate key lessons throughout text Short chapters offer focused discussion and clear ‘voice’

Epigenetics of Cancer Prevention

Epigenetics of Cancer Prevention
  • Author : Anupam Bishayee,Deepak Bhatia
  • Publisher :Unknown
  • Release Date :2018-11-27
  • Total pages :442
  • ISBN : 9780128125663
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Summary : Epigenetics of Cancer Prevention, Volume Ten is the first to look at epigenetics and chemoprevention together. Although there is numerous scientific data available on how epigenetics can lead to cancer and how chemoprevention can be beneficial in the treatment of, or improvement of quality of life, together they will set an advanced understanding for the reader in this upcoming field of chemoprevention influencing epigenetics. This book discusses molecular epigenetic targets of natural products, such as green tea polyphenols, curcumin and resveratrol, and organ specific epigenetic targets related to diverse types of cancer, for example prostate, colorectal, breast, lung and skin cancers. Additionally, it encompasses a discussion on research methods and limitations to study epigenetics and epigenomics of chemopreventive drugs and personalized cancer treatment with phytochemicals. The book is ideal for cancer researchers, health care professionals and all individuals who are interested in cancer prevention research and its clinical applications, especially in natural remedies. Lists natural agents, including nutraceuticals, and their effects on normal or tumor genome Addresses various epigenetic systems and mechanisms in the regulation and support of the mammalian genome Discusses how various parts of dietary phytochemicals can influence or modify epigenetic mechanisms in several types of cancer

Computational Epigenetics and Diseases

Computational Epigenetics and Diseases
  • Author : Anonim
  • Publisher :Unknown
  • Release Date :2019-02-06
  • Total pages :450
  • ISBN : 9780128145142
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Summary : Computational Epigenetics and Diseases, written by leading scientists in this evolving field, provides a comprehensive and cutting-edge knowledge of computational epigenetics in human diseases. In particular, the major computational tools, databases, and strategies for computational epigenetics analysis, for example, DNA methylation, histone modifications, microRNA, noncoding RNA, and ceRNA, are summarized, in the context of human diseases. This book discusses bioinformatics methods for epigenetic analysis specifically applied to human conditions such as aging, atherosclerosis, diabetes mellitus, schizophrenia, bipolar disorder, Alzheimer disease, Parkinson disease, liver and autoimmune disorders, and reproductive and respiratory diseases. Additionally, different organ cancers, such as breast, lung, and colon, are discussed. This book is a valuable source for graduate students and researchers in genetics and bioinformatics, and several biomedical field members interested in applying computational epigenetics in their research. Provides a comprehensive and cutting-edge knowledge of computational epigenetics in human diseases Summarizes the major computational tools, databases, and strategies for computational epigenetics analysis, such as DNA methylation, histone modifications, microRNA, noncoding RNA, and ceRNA Covers the major milestones and future directions of computational epigenetics in various kinds of human diseases such as aging, atherosclerosis, diabetes, heart disease, neurological disorders, cancers, blood disorders, liver diseases, reproductive diseases, respiratory diseases, autoimmune diseases, human imprinting disorders, and infectious diseases

Cancer and Noncoding RNAs

Cancer and Noncoding RNAs
  • Author : Jayprokas Chakrabarti,Sanga Mitra
  • Publisher :Unknown
  • Release Date :2017-10-13
  • Total pages :576
  • ISBN : 9780128134375
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Summary : Cancer and Noncoding RNAs offers an in-depth exploration of noncoding RNAs and their role in epigenetic regulation of complex human disease, most notably cancer. In addition to examining microRNAs, this volume provides a unique evaluation of more recently profiled noncoding RNAs now implicated in carcinogenesis, including lncRNAs, piRNAs, circRNAs, and tRNAs, identifying differences in function between these noncoding RNAs and how they interact with the rest of the epigenome. A broad range of chapters from experts in the field detail epigenetic regulation of various cancer types, along with recent next generation sequencing technologies, genome-wide association studies (GWAS) and bioinformatics approaches. This book will help researchers in genomic medicine and cancer biology better understand the role of noncoding RNAs in epigenetics, aiding in the development of useful biomarkers for diagnosis, prognosis and new RNA-based disease therapies. Provides a comprehensive analysis of noncoding RNAs implicated in epigenetic regulation of gene expression and chromatin dynamics Educates researchers and graduate students by highlighting, in addition to miRNAs, a range of noncoding RNAs newly associated with carcinogenesis Applies current knowledge of noncoding RNAs and epigenomics towards developing cancer and RNA-based disease therapies Features contributions by leading experts in the field

Toxicoepigenetics

Toxicoepigenetics
  • Author : Shaun D. McCullough,Dana Dolinoy
  • Publisher :Unknown
  • Release Date :2018-11-02
  • Total pages :428
  • ISBN : 9780128124345
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Summary : Toxicoepigenetics: Core Principles and Applications examines the core aspects of epigenetics, including chromatin biology, DNA methylation, and non-coding RNA, as well as fundamental techniques and considerations for studying each of these mechanisms of epigenetic regulation. Although its integration into the field of toxicology is in its infancy, epigenetics have taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration. Increasing the presence of epigenetics in toxicological research allows for a more in-depth understanding of important aspects of toxicology such as the role of the environment and lifestyle influencing the individual susceptibility to these effects and the trans-generational transmission of these health effects and susceptibilities. Methods chapters are included to help improve efficacy and efficiency of protocols in both the laboratory and the classroom. Toxicoepigenetics: Core Principles and Applications is an essential book for researchers and academics using epigenetics in toxicology research and study. Introduces the fundamental principles and practices for understanding the role of the epigenome in toxicology Presents the foundation of epigenetics for toxicologists with a broad range of backgrounds Discusses the incorporation of epigenetics and epigenomics into current toxicological studies and interpretation of epigenetic data in toxicological applications

Epigenetics and Cancer

Epigenetics and Cancer
  • Author : Fazlul H. Sarkar
  • Publisher :Unknown
  • Release Date :2013-05-29
  • Total pages :287
  • ISBN : 9789400766129
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Summary : Overall, this book illustrates the complexities of the regulation and deregulation of genes mediated through epigenetics in the development and progression of human malignancies. All the articles have been carefully chosen to represent several cancer systems with state of our knowledge on the role of epigenetic deregulation of microRNAs (miRNAs) and their target mRNAs along with epigenetic deregulation of mRNAs. This book also illustrates the role of several dietary agents, collectively called nutraceuticals or natural agents in modulating the epigenetic reprogramming of miRNAs and mRNAs for the prevention and/or treatment of human malignancies. It is well known that genetic aberrations, especially inherited through parents (somatic genetic alterations) contribute to the development of less than 10% of all cancer yet epigenetic alterations in genes especially through selective methylation and acetylation appears to be responsible for the development and progression of the vast majority of all cancers. Therefore, understanding the role of epigenetics in the regulation of genes especially through deregulated expression of miRNAs as presented in this book will allow scientists to devise targeted therapeutic strategies for re-expression of the lost genes or down-regulate the genes that are over-expressed in order to eradicate cancer. It is hoped that targeting epigenetics will not only target cancer cells but it will also target the tumor microenvironment (more like the entire tumor environment such as the entire host) for achieving better treatment outcomes for patients diagnosed with cancer which will lead to achieve the long-term objective for complete eradication of cancer. This book contains fifteen chapters which begins with the concept of systems and network biology for investigating the epigenetics of cancer followed by a series of articles on the role of miRNAs and their target genes in the biology of pancreatic cancer and other cancers such as breast, kidney, prostate and and colon. Since it is becoming increasingly clear that cancer stem cells (CSCs) are important in the development and progression of cancer, and CSCs are important in therapeutic resistance, treatment failure and tumor recurrence, thus the importance of CSCs and epigenetics has been highlighted by a very timely article on epigenetic variations of stem cell markers in cancer including miRNAs. Moreover, just targeting heterogeneous cancer cell populations may not be optimal to eradicate tumors and for which one must take a holistic approach for developing drugs that could also target the tumor microenvironment and tumor dormancy that are regulated through epigenetics. Keeping abreast with this thought process the concluding chapter provides a concept towards curative cancer therapy with maspin, which could be a unique window of opportunity to target tumor dormancy. Therefore, it suggest that targeting the tumor dormancy and the tumor microenvironment using novel therapeutics specifically by targeting epigenetics would become the future of medicine.

Nutritional Epigenomics

Nutritional Epigenomics
  • Author : Anonim
  • Publisher :Unknown
  • Release Date :2019-07-20
  • Total pages :478
  • ISBN : 9780128173107
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Summary : Nutritional Epigenomics offers a comprehensive overview of nutritional epigenomics as a mode of study, along with nutrition’s role in the epigenomic regulation of disease, health and developmental processes. Here, an expert team of international contributors introduces readers to nutritional epigenomic regulators of gene expression, our diet’s role in epigenomic regulation of disease and disease inheritance, caloric restriction and exercise as they relate to recent epigenomic findings, and the influence of nutritional epigenomics over circadian rhythms, aging and longevity, and fetal health and development, among other processes. Disease specific chapters address metabolic disease (obesity and diabetes), cancer, and neurodegeneration, among other disorders. Diet-gut microbiome interactions in the epigenomic regulation of disease are also discussed, as is the role of micronutrients and milk miRNAs in epigenetic regulation. Finally, chapter authors examine ongoing discussions of race and ethnicity in the social-epigenomic regulation of health and disease. Empowers the reader to employ nutritional epigenomics approaches in their own research Discusses the latest topics in nutritional epigenomics in the regulation of aging, circadian rhythm, inheritance and fetal development, as well as metabolism and disease Offers a full grounding in epigenetic reprogramming and nutritional intervention in the treatment and prevention of disease, as informed by population-based studies

Epigenetics and Dermatology

Epigenetics and Dermatology
  • Author : Qianjin Lu,Christopher C. Chang,Bruce C. Richardson
  • Publisher :Unknown
  • Release Date :2015-02-16
  • Total pages :520
  • ISBN : 9780128012727
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Summary : Epigenetics and Dermatology explores the role of epigenetics in the pathogenesis of autoimmune-related skin diseases and skin cancer. Leading contributors cover common and uncommon skin conditions in which extensive epigenetic research has been done. They explain how environmental exposures (chemicals, drugs, sunlight, diet, stress, smoking, infection, etc.) in all stages of life (from a fetus in-utero to an elderly person) may result in epigenetic changes that lead to development of some skin diseases in life. They also discuss the possibilities of new and emergent epigenetic treatments which are gradually being adopted in management of various skin diseases. Chapters follow a conventional structure, covering fundamental biology of the disease condition, etiology and pathogenesis, diagnosis, commonly available treatments, and epigenetic therapy where applicable. Discusses the basic biology of skin diseases and skin cancers induced or aggravated by aberrant epigenetic changes Evaluates how to approach autoimmune-related skin diseases from a therapeutic perspective using the wealth of emergent epigenetic clinical trials Offers a coherent and structured table of contents with basic epigenetic biology followed by discussion of the spectrum of rheumatologic through neoplastic skin diseases, finally ending with a discourse on epigenetic therapy

Epigenetic Alterations in Oncogenesis

Epigenetic Alterations in Oncogenesis
  • Author : Adam R. Karpf
  • Publisher :Unknown
  • Release Date :2012-09-06
  • Total pages :348
  • ISBN : 9781441999672
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Summary : The purpose of this book is to provide an up to date review of the nature and consequences of epigenetic changes in cancer. Epigenetics literally means “above” genetics, and consists of heritable gene expression or other phenotypic states not accounted for by DNA base sequence. Epigenetic changes are now known to make a large contribution to various aspects of tumorigenesis. These changes include alterations in global and promoter specific DNA methylation, activating and repressive histone modifications, and changes in higher order chromatin structures. Each of these topics will be covered in this book.

MicroRNAs in Diseases and Disorders

MicroRNAs in Diseases and Disorders
  • Author : Aurora Esquela-Kerscher,Philip V Peplow,George A Calin,Bridget Martinez
  • Publisher :Unknown
  • Release Date :2019-05-07
  • Total pages :480
  • ISBN : 9781788017817
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Summary : From pathology to treatment, MicroRNAs in Diseases and Disorders highlights the role of microRNAs (miRNAs) in the development and progression of a variety of diseases, including cancer, neurological disease, endocrine disease and autoimmune disease, and underscores the utilization of miRNA targets in the treatment of these conditions. Providing a comprehensive account, this book also includes the identification of miRNAs as diagnostic and prognostic biomarkers for disease, as well as evaluates translational value from clinical trials using synthesized and functionalized miRNA mimics and inhibitors. With a global contribution list and chapters from leading experts across the field, MicroRNAs in Diseases and Disorders is an invaluable reference to miRNA researchers and health professionals in a variety of disease areas in government, academia and industry. The book will also appeal to pharmaceutical and medicinal chemists with an interest in miRNA targeting therapeutics, as well as to advanced students in chemical biology and drug discovery.

Puberty from Bench to Clinic

Puberty from Bench to Clinic
  • Author : J.-P. Bourguignon,A.-S. Parent
  • Publisher :Unknown
  • Release Date :2015-12-17
  • Total pages :276
  • ISBN : 9783318027891
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Summary : Puberty is a unique paradigm for the understanding of gene-environment interaction and developmental programming. Therefore, normal and abnormal pubertal development can be divided and examined in three sections: the role of genetic factors, the role of environmental factors (including nutrition) and therapeutic issues in disorders of puberty. Dealing with all of these sections and framed along current key concepts in pediatric endocrinology, experts share their view on critical issues such as weighting of genetic versus environmental factors or the impact of environmental factors in relation to critical periods in development. Not only showing the consensus and controversial issues in the various areas, each chapter presents lessons for clinical management in an attempt to link basic research, physiology and pathophysiology with the clinical management of pubertal disorders. Puberty from Bench to Clinic bridges up-to-date concepts from animal and human physiology and pathology towards a better understanding and management of pubertal disorders, making it a unique resource for researchers in the field of development and reproduction, clinical scientists and practitioners in neuro-, pediatric and adolescent endocrinology as well as gynecology.

DNA Methylation Protocols

DNA Methylation Protocols
  • Author : Jörg Tost
  • Publisher :Unknown
  • Release Date :2018-08-30
  • Total pages :704
  • ISBN : 1493984993
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Summary : This third edition volume expands on the previous editions by providing a comprehensive update on the available technologies required to successfully perform DNA methylation analysis. The different technologies discussed in this book analyze the global DNA methylation contents, comprehensive analyses using various NGS based methods for genome-wide DNA methylation analysis, along with precise quantification of DNA methylation levels on single CpG positions. The chapters in this book are divided into 7 parts: an introduction to the field along with tips on study design and data analysis; global DNA methylation levels; genome-wide DNA methylation analysis; highly multiplexed target regions; locus-specific DNA methylation analysis; DNA methylation analysis of specific biological samples; and hydroxymethylation. Written in the highly successful Methods in Molecular Biology series format, 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. Cutting-edge and thorough, DNA Methylation Protocols, Third Edition is a valuable resource for postdoctoral investigators and research scientists who work with different aspects of genetics, and cellular and molecular biology, as well as clinicians who are involved in diagnostics or treatment of diseases with epigenetic components.

Gene Expression and Regulation in Mammalian Cells

Gene Expression and Regulation in Mammalian Cells
  • Author : Fumiaki Uchiumi
  • Publisher :Unknown
  • Release Date :2018-02-28
  • Total pages :372
  • ISBN : 9789535138679
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Summary : Sixty years after the "central dogma," great achievements have been developed in molecular biology. We have also learned the important functions of noncoding RNAs and epigenetic regulations. More importantly, whole genome sequencing and transcriptome analyses enabled us to diagnose specific diseases. This book is not only intended for students and researchers working in laboratory but also physicians and pharmacists. This volume consists of 14 chapters, divided into 4 parts. Each chapter is written by experts investigating biological stresses, epigenetic regulation, and functions of transcription factors in human diseases. All articles presented in this volume by excellent investigators provide new insights into the studies in transcriptional control in mammalian cells and will inspire us to develop or establish novel therapeutics against human diseases.

Non-coding RNAs and Epigenetic Regulation of Gene Expression

Non-coding RNAs and Epigenetic Regulation of Gene Expression
  • Author : Kevin V. Morris
  • Publisher :Unknown
  • Release Date :2012
  • Total pages :216
  • ISBN : 1904455948
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Summary : Non-coding RNAs potentially play an active role in modulating gene transcription and epigenetic states. Several genes in differentiated cells may be under some form of RNA-based transcriptional and epigenetic regulatory control. This form of regulation may be controlled by selective pressures and influence the adaptability of the cell. The concept that RNA can control epigenetic states impacts our understanding of the basic fabric of the cell and may have therapeutic potential. Many studies have been carried out on the modulation of gene transcription by non-coding RNAs. This book, written by a group of distinguished scientists, represents an important overview and summary of the field to date. The 13 chapters are organized into three sections: a) Non-coding RNAs: Form, Function and Diversity; b) Non-coding RNAs: Gene Regulation and Epigenetics; and c) Non-coding RNAs: Disease and Therapeutics. This up-to-date volume is an essential book for those working in the area and represents a major information resource on current research in the fast-moving fields of epigenetics, the regulation of gene expression, and RNA research.

Skeletal Muscle Development

Skeletal Muscle Development
  • Author : James G. Ryall
  • Publisher :Unknown
  • Release Date :2017-08-25
  • Total pages :226
  • ISBN : 1493972820
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Summary : This detailed volume presents a wide range of techniques that go beyond the standard assays typically used to assess Myogenesis. The content included addresses assays to analyze skeletal muscle gene expression, proliferating muscle cells, the process of myoblast fusion, muscle development (in vivo), as well as muscle repair. 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, Skeletal Muscle Development serves as an ideal guide to the study of this highly complex yet carefully regulated process.>

Epigenetics of B Cells and Antibody Responses

Epigenetics of B Cells and Antibody Responses
  • Author : Paolo Casali
  • Publisher :Unknown
  • Release Date :2016-04-12
  • Total pages :229
  • ISBN : 9782889197903
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Summary : Epigenetics is the study of changes in gene activity that are heritable but not caused by changes in the DNA sequence. By modulating gene activities, epigenetic changes regulate cell functions. They include DNA methylation, histone posttranslational modifications and gene silencing by the action of non-coding RNAs, particularly microRNAs. It is now clear that epigenetic changes regulate B cell development. By acting in concert with networks of transcription factors, they modulate the activation of B cell lineage specific gene programs and repress inappropriate gene transcription in particular B cell differentiation states.

A hallmark of B cell development in the bone marrow is the assembly of the B cell receptor (BCR) for antigen through rearrangement of immunoglobulin heavy (IgH) and light (IgL) chain V(D)J genes, as mediated by RAG1/RAG2 recombinases. Ig V(D)J rearrangement critically times the progression from pro-B cell to pre-B cell and, finally, mature B cell. Such progression is modulated by epigenetic marks, such as DNA methylation and histone posttranslational modifications, that increase chromatin accessibility and target RAG/RAG2 to V, D and J DNA. It is also dependent on the expression of multiple microRNAs. Mice deficient in Ago2, which is essential for microRNA biogenesis and function, have B cell development blocked at the pro-B cell stage. In agreement with this, B cell specific ablation of microRNA by B cell-specific knockout of Dicer virtually blocks B cell differentiation at the pro-B to pre-B cell transition.

After mature B cells encounter antigen, changes of the epigenetic landscape are induced by the same stimuli that drive the antibody response; such epigenetic changes underpin the maturation of the antibody response itself. They instruct those B cell differentiation processes, somatic hypermutation (SHM), class switch DNA recombination (CSR) and plasma cell differentiation, that are central to the maturation of the antibody response as well as differentiation of memory B cells. Inducible histone modifications, together with DNA methylation and microRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID), central to SHM and CSR, and B lymphocyte-induced maturation protein-1 (Blimp-1), which is central to plasma cell differentiation.

Combinatorial histone modifications also function as histone codes in the targeting of the CSR and, possibly, the SHM machinery to the Ig locus by recruiting specific adaptors (histone code readers) that can in turn target and/or stabilize CSR/SHM factors. Epigenetic alterations in memory B cells contribute to their functionally distinction from their naive counterparts. Memory B cells inherit epigenetic information from their precursors and acquire new epigenetic marks, which make these resting B cells poised to promptly respond to antigen. The cross/feedback regulation of different epigenetic modifications/elements further increases the complexity of the B cell epigenome, which interacts with the genetic information for precise modulation of gene expression. It is increasingly evident that epigenetic dysregulation in B cells, including aberrant expression of microRNAs, can result in aberrant antibody responses to microbial pathogens, emergence of pathogenic autoantibodies or B cell neoplastic transformation. Epigenetic marks are potential targets for new therapeutics in autoimmunity and B cell malignancy.