BookLuke B. Hesson, Antonia L. Pritchard, editors.
Summary: In genetic pathology, epigenetic testing is rare and under utilised. In this book, we introduce epigenetics to a non-expert scientific audience and describe current and future clinical utility of epigenetic testing. By focussing on epigenetics in human disease this book will guide professionals (scientists and clinicians) to understand how epigenetics is relevant in a clinical context, and to implement epigenetic testing in diagnostic laboratories. The book begins with a historical perspective of genetics and epigenetics and describes the work of pioneers who have helped shape these fields. The various mechanisms by which epigenetics can regulate the function of the genome is described. These include DNA methylation, histone modifications, histone variants, nucleosome positioning, cis-regulatory elements, non-coding RNAs and the three-dimensional organisation of chromatin in the nucleus. These are discussed in the context of embryological development, cancer and imprinting disorders, and include examples of epigenetic changes that can be used in diagnosis, prediction of therapeutic response, prognostication or disease monitoring. Finally, for those wishing to implement epigenetic testing in a diagnostic setting, the book includes a case study that illustrates the clinical utility of epigenetic testing.
Contents:
Intro; Preface; Epigenetics: A Lay Description; Epigenetics: A Scientific Description; Contents; About the Editors;
1: Genetics and Epigenetics: A Historical Overview; 1.1 The Early Origins of Genetics; 1.2 Discovery of DNA; 1.3 Early Characterisation of DNA; 1.4 Discovering That Genes Are Made of DNA; 1.5 The Birth and Evolution of Epigenetics; 1.6 The Double Helix Structure of DNA; 1.7 The Discovery of DNA Methylation; 1.8 The X-Chromosome and Its Unique Place in Genetics and Epigenetics; 1.9 Heritability of DNA Methylation; 1.10 Genomic Imprinting; 1.11 Why Do Genes Become Imprinted? 1.12 How Do Genes Become Imprinted?1.13 Histones, Nucleosomes and Chromatin Structure; 1.14 Cancer Epigenetics; 1.15 A Molecular Definition of the Term `Gene;́ 1.16 CpG Islands; 1.17 How Does DNA Methylation Cause Transcriptional Silencing?; 1.18 Epigenomics; 1.19 Key Milestones in Genetics and Epigenetics; 1.20 Key Discoveries; References;
2: The DNA Methylation Machinery; 2.1 DNA Methylation/Methylcytosine; 2.2 Readers of Methylcytosine: DNA Methylation and Gene Expression; 2.2.1 Methyl-CpG-Binding Domain Proteins (MBD); 2.3 Writers of Methylcytosine: DNA Methyltransferases (DNMTs) 2.3.1 The Function of DNMTs: Maintenance Methylation2.3.2 The Function of DNMTs: Establishment of DNA Methylation; 2.3.3 CpG Islands; 2.4 Erasers of Methylcytosine; 2.4.1 Regulation of DNA Demethylation by TET Enzymes; 2.5 Conclusion; References;
3: 5-Methylcytosine and Its Oxidized Derivatives; 3.1 Introduction; 3.2 DNA Methyltransferases; 3.3 The Function of 5-Methylcytosine; 3.4 Mutations in DNMT1; 3.5 Mutations in DNMT3A; 3.6 Mutations in DNMT3B; 3.7 5-Methylcytosine-Binding Proteins; 3.8 5-Methylcytosine Oxidases, the TET Proteins 3.9 Biological Role of 5-Hydroxymethylcytosine in Development and Disease3.10 Mutations in TET2; 3.11 Proteins That Bind to Oxidized 5-Methylcytosine Derivatives; References;
4: The Role of Nucleosomes in Epigenetic Gene Regulation; 4.1 Introduction; 4.2 The Role of the Nucleosome; 4.2.1 Nucleosome Remodelling; 4.2.2 Variant Nucleosomes; 4.3 Histone Post-Translational Modifications; 4.3.1 Histone Acetylation; 4.3.2 Histone Methylation; 4.4 DNA Methylation; 4.5 Transcription Regulation; 4.5.1 Promoters; 4.5.1.1 Histone Modifications at Promoters; 4.5.1.2 Histone Variants at Promoters 4.5.1.3 Nucleosome Positioning at Promoters4.5.1.4 DNA Methylation at Promoters; 4.5.1.5 Promoter Nucleosomes and Cancer; 4.5.2 Enhancers; 4.5.2.1 Histone Modifications at Enhancers; 4.5.2.2 Nucleosome Positioning at Enhancers; 4.5.2.3 DNA Methylation at Enhancers; 4.5.3 Gene Bodies; 4.5.3.1 Histone Modifications at Gene Bodies; 4.5.3.2 Nucleosome Positioning at Gene Bodies; 4.5.3.3 DNA Methylation at Gene Bodies; 4.5.4 Bivalent Chromatin; 4.5.4.1 Bivalent Promoters; 4.5.4.2 Bivalent Enhancers; 4.5.5 Nucleosome Asymmetry; 4.6 Future Directions; 4.7 Concluding Remarks; References