METHYLATION - FROM DNA, RNA AND HISTONES TO DISEASES AND TREATMENT Edited by Anica Dricu Methylation - From DNA, RNA and Histones to Diseases and Treatment http://dx.doi.org/10.5772/2932 Edited by Anica Dricu Contributors Anica Dricu, Dmitri Nikitin, Attila Kertesz-Farkas2, Alexander Solonin, Marina Mokrishcheva, Hirokazu Suzuki, Robert Peter Mason, Mark Brown, Xian Wang, Hongchuan Jin, Elena Kubareva, Alexandra Ryazanova, Liudmila Abrosimova, Tatiana Oretskaya, Zvonko Magic, Gordana Supic, Nebojsa Jovic, Mirjana Brankovic-Magic, Jianrong Li, Rita Castro, Byron Baron Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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Publishing Process Manager Iva Simcic Technical Editor InTech DTP team Cover InTech Design team First published February, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Methylation - From DNA, RNA and Histones to Diseases and Treatment , Edited by Anica Dricu p. cm. ISBN 978-953-51-0881-8 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Section 1 Gene Expression and Methylation 1 Chapter 1 Breaking the Silence: The Interplay Between Transcription Factors and DNA Methylation 3 Byron Baron Section 2 DNA-Methyltransferases: Structure and Function in Eukaryotic and Prokaryotic System 27 Chapter 2 Diverse Domains of (Cytosine-5)-DNA Methyltransferases: Structural and Functional Characterization 29 A. Yu. Ryazanova, L. A. Abrosimova, T. S. Oretskaya and E. A. Kubareva Chapter 3 Bifunctional Prokaryotic DNA-Methyltransferases 71 Dmitry V. Nikitin, Attila Kertesz-Farkas, Alexander S. Solonin and Marina L. Mokrishcheva Section 3 Protein Arginine Methylation in Mammals 89 Chapter 4 Deciphering Protein Arginine Methylation in Mammals 91 Ruben Esse, Paula Leandro, Isabel Rivera, Isabel Tavares de Almeida, Henk J Blom and Rita Castro Section 4 Cancer Research Through Study of Methylation Cell Processes 117 Chapter 5 Methylation in Tumorigenesis 119 Melissa A. Edwards, Pashayar P. Lookian, Drew R. Neavin and Mark A. Brown VI Contents Chapter 6 Circulating Methylated DNA as Biomarkers for Cancer Detection 137 Hongchuan Jin, Yanning Ma, Qi Shen and Xian Wang Chapter 7 DNA Methylation, Stem Cells and Cancer 153 Anica Dricu, Stefana Oana Purcaru, Alice Sandra Buteica, Daniela Elise Tache, Oana Daianu, Bogdan Stoleru, Amelia Mihaela Dobrescu, Tiberiu Daianu and Ligia Gabriela Tataranu Chapter 8 DNA Methylation in the Pathogenesis of Head and Neck Cancer 185 Zvonko Magić, Gordana Supić, Mirjana Branković-Magić and Nebojša Jović Section 5 Bacteria, Viruses and Metals Methylation: Risk and Benefit for Human Health 217 Chapter 9 Host-Mimicking Strategies in DNA Methylation for Improved Bacterial Transformation 219 Hirokazu Suzuki Chapter 10 Messenger RNA Cap Methylation in Vesicular Stomatitis Virus, a Prototype of Non‐Segmented Negative‐Sense RNA Virus 237 Jianrong Li and Yu Zhang Chapter 11 The Methylation of Metals and Metalloids in Aquatic Systems 271 Robert P. Mason Preface There is a widespread interest in the today scientific literature for methylation field, which started to be published in the early 60’s and continues to be a future line of research. This book represents a comprehensively reviewed literature on the importance of methylation processes in human health and disease. The book, covers the basic mechanism of DNA and protein methylation, along with the role of mRNA cap methylation in viral replication, gene expression and viral pathogenesis. Human health risks from metals methylation in the natu‐ ral environment has been well describe in the literature. As a consequence, the formation processes, the biotic and abiotic degradation and the accumulation of the methylated metals and metalloids in the aquatic environment is reviwed in the book. DNA methylation is a well-characterized process, allowing cells to control gene expression, while the study of histone methylation is more recent. The enzymes responsible for histone methylation (histone methyltransferases and histone demethylases) are important for tran‐ scriptional regulation in both normal and abnormal states, representing an important target for drug discovery. The interconection between DNA methylation and other regulatory mol‐ ecules such as: enzymes, transcription factors, proteins and growth factors is discussed, pro‐ viding key information about the mechanisms that trigger cell proliferation, differentiation, aging and malignant transformation. This textbook strongly point out the importance of me‐ thylated DNA as a biological marker of cancer an also gives the reader insights into the re‐ cently emerged treatment modalities targeting methylation mechanism, in various diseases including cancer. The textbook addresses the following topics: Gene expression and methylation, DNA-meth‐ yltransferases: structure and function in eukaryotic and prokaryotic system; Protein arginine methylation in mammals; Cancer research through study of methylation cell processes; Bac‐ teria, viruses and metals methylation: risk and benefit for human health. The book aims at the advanced undergraduate and graduate biomedical students and re‐ searchers working in the epigenetic area, providing readers with both classical and relevant recent discoveries that have been made in the research field of methylation and also point‐ ing out pathways where questions remain. Prof. Anica Dricu University of Medicine and Pharmacy Faculty of Medicine Craiova, Romania Section 1 Gene Expression and Methylation Chapter 1 Breaking the Silence: The Interplay Between Transcription Factors and DNA Methylation Byron Baron Additional information is available at the end of the chapter http://dx.doi.org/10.5772/55021 1. Introduction DNA methylation is best known for its role in gene silencing through a methyl group (CH3) being added to the 5' carbon of cytosine bases (giving 5-methylcytosine) in the promoters of genes leading to supression of transcription [1]. However this is far from the whole story. De novo methylation, which involves the addition of a methyl group to unmodified DNA, is described as an epigenetic change because it is a chemical modification to DNA not a change brought about by a DNA mutation. Unlike mutations, methylation changes are potentially reversible. Epigenetic changes also include changes to DNA-associated molecules such as histone modifications, chromatin-remodelling complexes and other small non-coding RNAs including miRNAs and siRNAs [2]. These changes have key roles in imprinting (gene-ex‐ pression dependent on parental origin), X chromosome inactivation and heterochromatin formation among others [3-5]. DNA methylation leading to silencing is a very important survival mechanism used on re‐ petitive sequences in the human genome, which come from DNA and RNA viruses or from mRNA and tRNA molecules that are able to replicate independently of the host genome. Such elements need to be controlled from spreading throughout the genome, by being si‐ lenced through CpG methylation, as they cause genetic instability and activation of onco‐ genes [6-10]. Such elements can be categorised into three groups: SINEs (Small Interspersed Nuclear Elements), LINEs (Long Interspersed Nuclear Elements) and LTRs (Long Terminal Repeats) [6,11-13]. Repetitive sequences are recognised by Lymphoid-Specific Helicase (LSH) also known as the ‘heterochromatin guardian’ [14,15], which additionally acts on sin‐ gle-copy genes [16]. © 2013 Baron; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 4 Methylation - From DNA, RNARNA andand Histones Histones to to Diseases Diseases and and Treatment Treatment DNA methylation generally occurs when a cytosine is adjacent 5’ to a guanine, called a CpG di‐ nucleotide. Such dinucleotides are spread all over the genome and over 70% of CpGs are me‐ thylated. Clusters of CpGs, called CpG Islands (CGI), consist of stretches of 200–4000bp that are 60 to 70% G/C rich, found in TATAless promoters and/or first exons of genes [17-19]. In the human genome almost 50% of transcription start sites (TSS) [20], and about 70% of all genes contain CGIs [21,22]. CGIs present in the promoters or first exons