Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Abstract

This book will focus on DNA and histone methylation in epigenetics and describe how it is involved in the molecular mechanisms responsible for the development of cancer. Chapters will summarize the current knowledge of the molecular basis of DNA and histone methylation and explain how it is involved in cancer, describe the features of DNA and histone methylation associated with particular types of cancer, diagnostic/therapeutic applications, and future directions of DNA and histone methylation as cancer targets. Foreword; Contents; DNA and Histone Methylation in Epigenetics; 1 Introduction; 2 DNA Methylation; 2.1 DNA Methylation in Mammals; 2.2 DNA Methyltransferase; 2.3 Methylated DNA Binding Protein; 2.4 Function of DNA Methylation; 3 Histone Methylation; 3.1 Methylation Sites; 3.2 Histone Methyltransferases; 3.3 Methylated Histone Binding Protein; 3.4 Function of Histone Methylation; 4 Perspective; References; Part I: DNA Methylation and Cancer; The Molecular Basis of DNA Methylation; 1 Introduction; 2 DNA Methylation and Gene Silencing; 3 DNA Methyltransferases in Mammals 3.1 Proposed Mechanism of Methylation Reaction3.2 Establishment of DNA Methylation Patterns; 3.2.1 Properties of the de novo Methyltransferases Dnmt3a and 3b; 3.2.2 Structural Properties of Dnmt3; 3.2.3 Sequence Specificity of de novo Methyltransferases; 3.2.4 Factors that Guide Dnmt3 to Target Sites for Methylation; 3.2.5 Function of Dnmt3L in Establishing DNA Methylation Patterns; 3.2.6 Chromatin Structure and Establishment of DNA Methylation; 3.3 Maintenance DNA Methylation; 3.3.1 Structure and Properties of Dnmt1; 3.3.2 Factors Necessary for Maintenance DNA Methylation 3.3.3 Exceptional Expression of Dnmt1 and Its Localization3.4 Cross-Talk Between de novo- and Maintenance-Type DNA Methyltransferases; 4 Modifications of Dnmts; 5 DNA Methylation and Aging; 6 Inhibitors of Dnmts; 7 DNA Demethylation; 8 Perspective; References; The Molecular Basis of DNA Demethylation; 1 Introduction; 2 DNA Methylation Machinery; 3 Passive and Active DNA Demethylation; 4 TET-Mediated Oxidative DNA Demethylation; 4.1 TET Family Dioxygenases; 4.2 TET-Mediated Iterative Oxidation of 5mC; 4.3 TDG-Mediated Excision of 5fC/5caC 4.4 Replication-Dependent Dilution of 5mC Oxidation Derivatives4.5 Other Potential TET-Initiated Active DNA Demethylation Pathways; 5 Potential TET-Independent Active DNA Demethylation Mechanisms; 6 Regulation of TET-Mediated DNA Demethylation; 6.1 Regulation of TET Expression; 6…