Environmental epigenomics and the human imprintome

For years many have believed that genetic heritage defined one's destiny, if an individual would grow to be healthy, or if he or she would suffer from chronic illness or cancer. Recent scientific evidence and the field of epigenetics has proven this to be untrue. Certainly, the DNA sequence and the genetic code are fixed; but the field of epigenetics has shown how methylation and other chemical modifications of the genome directly influence the production of proteins that can alter the phenotype of an organism. This article will lay out the supporting research, the details on how the internal and external environments influence genetic function, and will allow the reader to develop an action plan necessary to influence the genetic code, with the goal of then moving the individual toward optimal health. These research details will enable health care professionals in every field of medicine to work with patients on positively influencing the genetic output in order to improve the quality of life and longevity.

The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that the prenatal and early postnatal environments shape the future ­probability of physical and mental wellbeing and risk of disease. A wealth of epidemiologic data supports the associations between maternal malnutrition, intrauterine growth retardation, and birthweight, and the risk of chronic disease including ­cardiovascular disease, hypertension, type 2 diabetes mellitus, obesity, neuropsychiatric disorders, and cancer. While the mechanisms underlying these observations remain unresolved, the DOHaD model assumes a developmental plasticity that allows adaptive regulation of the embryonic, fetal, and/or early postnatal metabolism in response to nutritional and environmental perturbations. Establishment of the epigenome coincides with vulnerable phases in development and provides one potential mechanism for long-lasting responses to transient environmental stimuli. Future studies in epigenetic epidemiology will seek to understand the role of various epigenetic mechanisms in DOHaD.

Epigenetics in teleost fish: From molecular mechanisms to physiological phenotypes.

The field of Epigenetics is rapidly evolving, such that the pace of our advances in the knowledge and understanding of this phenomenon often outstrips the basic teaching literature. In the preface to this book, the author describes the rationale for the book was to develop a text that would provide an “easily digestible text that could provide an introduction to the subject of epigentics.” In essence, this is what this book does provide, as it is an easily read and understandable piece of work which introduces the novice to the world of epigenetics. The book is split over 16 chapters into three main areas or sections. The first section deals with the general issues on how epigenetic regulation/modification is achieved with an introduction to basic chromatin structure and key concepts relating to the issues of regulating transcription, followed by how this regulation can be achieved through the auspices of the epigenetic machinery. There are eight chapters associated with this section dealing with various elements including chapters on chromatin (Chapters 3 and 4), DNA methylation (Chapter 5), Histone post-translational modifications (Chapter 6), and on Locus-specific control of chromatin structure (Chapter 8). Having covered this, the reader is then brought into the second section of the book which deals with how epigenetics controls cellular functions, with five specific chapters on issues such as cell-specific gene expression (Chapter 9), the role of epigenetics in the regulation of the mitotic cell cycle (Chapter 10), the basis of genomic imprinting (Chapter 11, and an absolute requisite chapter for a book on epigenetics), through the role of epigenetics in cellular differentiation and reprogramming. In this regard the book is well represented as this is the authors area of speciality, and the chapters entitled “Epigenetic Control of Cellular Differentiation” (Chapter 12) and “Reversibility of Epigenetic Modification Patterns” (Chapter 13) nicely discuss the role of epigenetics and the potential clinical implications of aberrant epigenetics in both cellular reprogramming and induced pluripotent stem cell (iPSC) production. The final section has three chapters discussing the evidence for the various roles of epigenetics with disease development and progression. The main critique of this section is the paucity of chapters. There are only three chapters linking the wealth of information now linking epigenetics with disease. Chapter 14 is entitled “epigenetic predisposition to disease and imprinting based disorders.” The author briefly touches on predisposition briefly mentioning epidemiology and the potential role of epigenetics as a cause of stochastic variation in disease. Imprinting based disorders are discussed in more detail with emphasis on some of the “classical” examples of such disorders (Prader-Willi and Angelman syndrome) followed by Beckwith-Wiedemann and Silver-Russell syndromes. The areas dealing with epigenetics of major disease groups is in fact fairly limited and focuses primarily on cardiovascular disease with smaller texts on kidney disease and diabetes, with some of the evidence for epigenetics simply described for each. Admittedly in this chapter summary the author notes this limitation. Chapter 15 deals with the roles of epigenetics within the neuronal setting. The introductory sections dealing with the roles of epigenetics and memory formation is nicely written. Two examples of the role of epigenetics in neurodegeneration are discussed (Alzheimers and Parkinson's disease), and the potential role of epigenetics in mental health is discussed fairly superficially in relation to bipolar disorders and depression. While there is some discussion on the effects of cocaine on epigenetics in relation to depression, there is no discussion on how epigenetics may play roles in drug addiction. The final chapter deals with “Epigenetics of Cancer” (Chapter 16), a daunting task for any author. Not unexpectedly, this chapter was unfortunately very superficial discussing in general terms the roles of aberrant DNA CpG Methylation and histone post-translational modification patterns in cancer. There was some discussion of the role of miRNAs in regulating DNA methyltransferases but no real discussion on the roles of miRNAs and lncRNAs in cancer. There was no chapter on the available data relating to the discovery and development of the currently licensed FDA approved epigenetic targeting agents and the current excitement within the field moving forward with the novel agents currently being developed for various epigenetic “readers,” “writers,” and “erasers.” Nevertheless, the book itself is well written, easy to read and more importantly easily understood. There are elements of this book which shine, and conversely elements that grate, particularly for those familiar or expert within the field. It is not perfect, but overall, this book represents an excellent primer for the complete novice, or for instructors who wish to introduce the topic of epigenetics to students with little or no knowledge of the topic.

The field of epigenetics is currently one of the most rapidly expanding in biology and has resulted in increasing public interest in its applications to human health. Epigenetics provides a promising avenue for both targeted individual intervention and public health messaging. However, to develop effective strategies for engagement, it is important to understand the public's understanding of the relevant concepts. While there has been some research exploring the public's understanding of genetic and environmental susceptibility to disease, limited research exists on public opinion and understanding of epigenetics and epigenetic concepts. Using an online questionnaire, this study investigated the Australian public's understanding, views, and opinions of epigenetics and related concepts, including the concepts of the developmental origins of health and disease (DOHaD) and the first 1000 days. Over 600 questionnaires were completed, with 391 included in the analysis. The survey included questions on knowledge of epigenetics and perceptions of epigenetic concepts for self and for children. Data were analyzed using predominately descriptive statistics, with free-text responses scored based on concordance with predetermined definitions. While participants' recognition of epigenetic terms and phrases was high, their understanding was limited. The DOHaD theory was more accurately understood than the first 1000 days or epigenetics itself. Female participants without children were more likely to recognize the term epigenetics, while age also had an impact. This research provides a solid foundation for further detailed investigation of these themes, all of which will be important data to help inform future public health messages regarding epigenetic concepts.

The Developmental Origins of Health and Disease (DOHaD) hypothesis studies the short- and long-term consequences of the conditions of the developmental environment for phenotypic variations in health and disease. Central to this hypothesis is the idea of interdependence of developmental influences, genes, and environment. Developmental programming effects are mediated by alterations in fundamental life functions, and the most enduring effects seem to occur if the main regulatory instances of the organ - the (epi)genome and the brain - are affected. Some new insights in the role of chromatin, in cellular development and differentiation, and neural plasticity from the field of epigenetics are introduced, followed by a section on epigenetics and brain development. It is proposed to extend the DOHaD hypothesis into the 'Developmental Origins of Behaviour, Health, and Disease' (DOBHaD) concept. Pregnancy and the early postnatal period are times of both great opportunity and considerable risk, and their influence can extend over a lifetime. The DOBHaD hypothesis opens fundamental new perspectives on preventing diseases and disorders.

The field of epigenetics is currently garnering a great deal of interest, exploring how our very molecular makeup in the form of modifications to the genome can be altered by factors as diverse as aging, disease, nutrition, stress, alcohol, and exposure to pollutants. Epigenetic changes have previously been implicated in the etiology of a variety of diseases, notably in the development of certain cancers, and inherited growth disorder syndromes, but the exploration of epigenetics’ role in fetal programming is still in its infancy. This chapter focuses on how nutritional exposures during pregnancy may affect the infant epigenome, and the impact that such modifications may have on the long-term health of the child. We start by describing some keys concepts in epigenetics and discuss windows of epigenetic plasticity in the context of the developmental origins of health and disease (DOHaD) hypothesis. We then review some of the key mechanisms by which nutrition can affect the epigenome, with a particular focus on the role of one-carbon metabolism. We finish by outlining some of the child health outcomes that have been linked to epigenetic dysregulation, and discuss possible next steps that need to be realized if insights into the basic science of epigenetics are to be translated into tangible public health benefits.

Role of epigenetics in carcinogenesis: Recent advancements in anticancer therapy

The book aims to provide an overview of current knowledge regarding epigenetics and epigenomics. Included are reviews on the role of epigenetics in the development and pathogenesis of the vascular endothelium and nervous system, as well as our current understanding of the potential etiologies of Autism Spectrum Disorders. Additional chapters are devoted to DNA methylation, genomic imprinting and human reproduction. A discussion of the role of the epigenome in cancer prevention and polyphenols is also included. Authors provide research findings from both human data and animal model studies. This book will be of interest to scientists, physicians and lay readers wishing to review recent developments in the field of epigenetics and epigenomics.

1.1 Epigenetics and cancer: An overview Genetic and epigenetic alterations are hallmarks of human cancer. In the last few decades, it has been well established that epigenetic changes are important events in human cancer development and progression in addition to genetic alterations (such as chromosomal rearrangements, aneuploidies and point mutations). Epigenetics refers to the study of changes in gene expression that are determined by mechanisms other than changes in the DNA sequence. Epigenetic phenomena include X-chromosome inactivation, genomic imprinting, cellular differentiation and the maintenance of cell identity. These events are mediated by several molecular mechanisms, including DNA methylation, post-translational histone modifications and various RNA-mediated processes. Many studies in the field of epigenetics have focused on the effects of histone modifications and DNA methylation in the transcription process because these mechanisms are often linked and interdependent (Ballestar, 2011). A variety of methods are currently being applied to detect epigenetic changes, and the past two decades have shown an exponential increase in novel approaches aimed at elucidating the molecular basis of epigenetic inheritance. DNA methylation is the most well studied epigenetic modification in human diseases (Fernandez et al., 2011). It involves the addition of a methyl group to the 5 carbon of a cytosine that is immediately followed by one guanine; i.e., DNA methylation typically occurs in a CpG dinucleotide context. CpG dinucleotides are generally underrepresented in the genome due to the increased mutation frequencies of the methylcytosines that are spontaneously converted to thymines. However, within the regions that are known as CpG islands, these dinucleotides are found at higher frequencies than is expected. It is believed that the human genome is comprised of approximately 38,000 CpG islands, and a large proportion of them (~37%) are located in the 5’ gene regulatory regions (promoters). The aberrant content of DNA methylation (global genome hypomethylation) and patterns of cytosine methylation, especially hypermethylation in promoter-associated CpG islands, are known to be associated with cancer. Gene-specific promoter hypermethylation causes the breakdown of normal cell physiology by silencing tumor suppressor genes, while DNA hypomethylation can reactivate oncogenes and repetitive sequences of the genome and lead to chromosomal instability (Sawan et al., 2008).

Chapter 7 - Maternal Prenatal Stress and the Developmental Origins of Mental Health: The Role of Epigenetics

AimsTo describe change in self-reported diet and plasma vitamin C, and to examine associations between change in diet and cardiovascular disease risk factors and modelled 10-year cardiovascular disease risk in the year following diagnosis of Type 2 diabetes.MethodsEight hundred and sixty-seven individuals with screen-detected diabetes underwent assessment of self-reported diet, plasma vitamin C, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multivariable linear regression was used to quantify the association between change in diet and cardiovascular disease risk at 1 year, adjusting for change in physical activity and cardio-protective medication.ResultsParticipants reported significant reductions in energy, fat and sodium intake, and increases in fruit, vegetable and fibre intake over 1 year. The reduction in energy was equivalent to an average-sized chocolate bar; the increase in fruit was equal to one plum per day. There was a small increase in plasma vitamin C levels. Increases in fruit intake and plasma vitamin C were associated with small reductions in anthropometric and metabolic risk factors. Increased vegetable intake was associated with an increase in BMI and waist circumference. Reductions in fat, energy and sodium intake were associated with reduction in HbA1c, waist circumference and total cholesterol/modelled cardiovascular disease risk, respectively.ConclusionsImprovements in dietary behaviour in this screen-detected population were associated with small reductions in cardiovascular disease risk, independently of change in cardio-protective medication and physical activity. Dietary change may have a role to play in the reduction of cardiovascular disease risk following diagnosis of diabetes.

The Future of Environmental Epigenetics: Insights Using the Clonal Water Flea Model

Downregulation of long noncoding RNA UCA1 is involved in Het-1A cells malignant transformation induced by N-nitrosamines combined microcystin-LR

Epigenetic analytical approaches in ecotoxicological aquatic research