Patho Epigenetics Of Disease

In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences. Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to “remember” their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of human diseases.

Epigenetic modification of cellular genomes is a fascinating means of regulating tissue- and cell type-specific gene expression in all developmental stages of the life of an organism. Carefully orchestrated processes, such as DNA methylation and a plenitude of specific histone modifications secure the faithful transmission of gene expression patterns to progeny cells. Upon chronic infection, the epigenetic cellular balance can become disrupted and, in the long run, through the epigenetic reprogramming of host cell genomes, contribute to the malignant conversion of formerly healthy cells, in many cases preceded by the establishment of an epigenetic field of cancerization. The present volume undertakes to highlight the interactions of infectious pathogens and their effector molecules with the epigenetic regulatory machinery of the cell. Clearly, the recent take-off of epigenetics research did not leave Research on Infectious Diseases and Infection-Associated Cancer untouched. This resulted in a great many of clinically relevant data on understanding the molecular mechanisms of chronic infectious disease. Infectious pathogen- and disease-specific epigenetic alterations are already being used for the early detection of malignant disease and for the prediction of chemotherapy resistance or response to treatment.

In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences. Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to “remember” their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of human diseases.

The present volume of Epigenetics and Human Health is devoted to the patho-epigenetics of viral and microbial infections, an exiting new field of disease-related epigenetic research. As recognized during the past years, epigenetic reprogramming of pathogen and host genome functions – the latter frequently induced by pathogens – plays an important role in many infectious processes. Beyond their immediate relevance for pathogen proliferation and obligatorily associated symptoms, such alterations frequently contribute to severe additional complications, such as the development of immunodeficiency, cancer and various chronic disorders. This holds in particular for epigenetic dysregulation of host gene expression induced by latent infections. The present book summarizes current knowledge of the mechanisms underlying epigenetic changes caused by viral, bacterial, fungal and protozoan infections and their impact on human health.

This important book explores recent research by experts in the field pertaining to the role played by genetic factors in human pathology. A range of perspectives creates a well-rounded picture, including: host-pathogen interactions causal relationships between genes and the environment the effects of environmental chemicals on gene expression DNA methylation The book also covers the analysis and provides models for understanding the epigenetics-pathology connection. This book is designed for use by senior undergraduate and graduate students from several disciplines such as general, molecular, cellular biology, genetics, genomics, proteomics, and bioinformatics. It will also serve as a reference book for existing researchers and new investigators entering this rather unexplored field.

There are now compelling human epidemiological and animal experimental data that indicate the risk of developing adult-onset complex diseases and neurological disorders are influenced by persistent epigenetic adaptations in response to prenatal and early postnatal exposures to environmental factors. Epigenetics refers to heritable changes in gene function that occur without a change in the sequence of the DNA. The main components of the epigenetic code are DNA methylation, histone modifications, and non-coding RNAs. The epigenetic programs are established as stem cell differentiate during embryogenesis, and they are normally faithfully reproduced during mitosis. Moreover, they can also be maintained during meiosis, resulting in epigenetic transgenerational disease inheritance, and also potentially introducing phenotypic variation that is selected for in the evolution of new species. The objective of this book is to provide evidence that environmental exposures during early development can alter the risk of developing medical conditions, such as asthma, autism, cancer, cardiovascular disease, diabetes, obesity, and schizophrenia later in life by modifying the epigenome.

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

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