Protein Complexes That Modify Chromatin

An early view of eukaryotic chromosomes was that of static structures, which stored DNA not in use within a given cell type. It was thought that packaging of DNA into higher levels of chromatin structure would suffice to repress gene expression and that the challenge to the cell would be to rescue specific sequences from these structures. The exten sive packaging of inactive DNA was considered the primary difference between eukaryotic and prokaryotic genomes and except for that point both would be similarly regulated by cis-acting sequences and trans acting factors. Our view of eukaryotic chromosomes has evolved dra matically over the last decade. The picture of chromosomes that is emerging is that of dynamic breathing organelles actively regulating the flow of genetic information from the genome. Indeed chromatin is so fluid that even maintaining gene quiescence is an active process and is tightly regulated. Chromatin dynamics is a consequence of protein complexes that modify histones, remove histone modifications, mobi lize nucleosomes or stabilize nucleosomes. Awide variety of such com plexes have now been described. Some are abundant and may play glo bal roles in chromosome fluidity and function. Others are more rare and specialized for specific functions at discreet loci. Moreover, several complexes share biochemical activities and genetic studies suggest overlapping functions in vivo. Many components of these complexes were first revealed in genetic screens, while others were discovered by novel cell biological or biochemical approaches.

​​​​​​​​​​​​​​​​​​​​​​​ Epigenetic modifications underlie all aspects of human physiology, including stem cell renewal, formation of cell types and tissues. They also underlie environmental impacts on human health, including aging and diseases like cancer. Consequently, cracking the epigenetic "code" is considered a key challenge in biomedical research. Chromatin structure and function are modified by protein complexes, causing genes to be turned “on” or “off” and controlling other aspects of DNA function. Yet while there has been explosive growth in the epigenetics field, human chromatin-modifying machines have only recently started to be characterized. To meet this challenge, our book explores complementary experimental tracks, pursued by expert international research groups, aimed at the physical and functional characterization of the diverse repertoire of chromatin protein machines - namely, the "readers, writers and erasers" of epigenomic marks. These studies include the identification of RNA molecules and drugs that interact selectively with components of the chromatin machinery. What makes this book distinctive is its emphasis on the systematic exploration of chromatin protein complexes in the context of human development and disease networks.

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

This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease

The term "chromatin remodelling" is widely used to describe changes in chromatin structure which is controlled by histone-modifying enzymes, chromatin remodelling complexes, non-histone DNA-binding proteins and noncoding RNAs. Many human diseases such as cancer, various genetic syndromes, autism and infectious disease have been linked to the disruption of these control processes by genetic, environmental or microbial factors. Therefore, to unravel the mechanisms by which they operate is one of the most exciting and rapid developing fields of modern biology and will contribute to new ways in treatment of these diseases. The chapters in this book will focus on recent advances in our understanding of the mechanisms that govern the dynamic structural of chromatin, thereby providing important insights into gene regulation, DNA repair, and human diseases.

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

This volume focuses on the relevance of epigenetic mechanisms in autoimmune disease. It provides new directions for future research in autoimmune disease.