Open Access Medical Books

TEXTBOOK : DNA METHYLATION – FROM GENOMICS TO TECHNOLOGY

DNA METHYLATION

Edited by Tatiana Tatarinova and Owain Kerton .

400 pages . 
Open Access . 

The term epigenetic was coined in 1957 by Conrad Hal Waddington, who is considered to be the last Renaissance biologist. Epigenetics is defined as the study of changes in gene expression due to mechanisms other than structural changes in DNA; that is changes arisen are not as a result of a change in the nucleotide sequence. Epigenetics is consequently used to explain phenomena which cannot be explained by the result of standard genetic mutations, for example, hereditary changes in gene expression as a result of environmental factors.
DNA methylation is one example of such a structural change which affects gene expression. Methylation occurs through the addition of a chemical methyl group (- CH3) in a covalent bond to the cytosine bases of the DNA backbone and typically occurs at a Cysteine-phosphate-Guanine- (CpG) dinucleotide1. DNA methylation is common in humans, where 70 to 80% of CpG dinucleotides are methylated. Generally, methylation occurs in noncoding sequences subsequently having little effect on gene expression. Interestingly, in "simple" organisms, such as yeast and fruit fly, there is little or no DNA methylation.
DNA methyltransferases (DNMTs), are the enzyme family which catalyses the methylation process which they do by , recognizing palindromic dinucleotides of CpG. There are a number of different groups of DNMTs and three DNMTs have been identified to operate in mammals. DNMT1, DNMT3A, and DNMT3B. A fourth similar enzyme (DNMT2 or TRDMT1) has been identified which is structurally similar to the other DMNTs, however, it causes no detectable effect on the total DNA methylation, suggesting that this enzyme has little role in DNA methylation. Interestingly, the genome of Drosophila contains a single DNMT gene, which most closely resembles mammalian DNMT2.
DNA methylation of CpG dinucleotides is essential for plant and mammalian development by mediating the expression of genes and plays a key role in X inactivation, genomic imprinting, embryonic development, chromosome stability, chromatin structure and may also be involved in the immobilization of transposons implications, for example the gain or loss of DNA methylation can produce loss of genomic imprinting and result in diseases such as Beckwith-Wiedermann syndrome, Prader-Willi syndrome or Angelman syndrome.
Changes in the pattern of DNA methylation are commonly seen in human tumors.
Both genome wide hypomethylation (insufficient methylation) and region-specific hypermethylation (excessive methylation) have been suggested to play a role in carcinogenesis2. A common cause of the loss of tumor-suppressor miRNAs in cancer is the silencing of primary transcripts by CpG island promoter by hypermethylation3.
DNA hypomethylation also contributes to cancer development via three major mechanisms, such as: an increase in genomic instability, reactivation of transposable elements and loss of imprinting.
Presence of epigenetic marks enables cells with the same genotype have potential to display different phenotypes and differentiate into many cell-types with different functions, and responses to environmental and intercellular signaling. For example, DNA methylation is essential for the process of imprinting. Imprinted genes are expressed from only one parental allele. This mono-allelic gene expression is directed by epigenetic marks established in the mammalian germ line and a single mutation, either genetic or epigenetic, can cause disease. There is an increased prevalence of imprinting disorders associated with human assisted reproductive technologies.
This books highlights the methods and mechanisms by which epigenetics with a focus on DNA methylation can be studied and its impacts on health.....

Dr Tatiana Tatarinova and Dr Owain Kerton
University of Glamorga
UK

CONTENTS : 


Part 1 of the textbook : Epigenetics Technology and Bioinformatics .

 1 Modelling DNA Methylation Dynamics 3
Karthika Raghavan and Heather J. Ruskin

 2 DNA Methylation Profiling from High-Throughput Sequencing Data 29
Michael Hackenberg, Guillermo Barturen and José L. Oliver

 3 GC3 Biology in Eukaryotes and Prokaryotes 55
Eran Elhaik and Tatiana Tatarinova

 4 Inheritance of DNA Methylation in Plant Genome 69
Tomoko Takamiya, Saeko Hosobuchi, Kaliyamoorthy Seetharam, Yasufumi Murakami
and Hisato Okuizumi

 5 MethylMeter®: A Quantitative, Sensitive, and Bisulfite-Free Method for Analysis of DNA Methylation 93
David R. McCarthy, Philip D. Cotter, and Michelle M. Hanna


Part 2 of the textbook : Human and Animal Health .


 6 DNA Methylation in Mammalian and Non-Mammalian Organisms 119
Michael Moffat, James P. Reddington, Sari Pennings and Richard R. Meehan

 7 Could Tissue-Specific Genes be Silenced in Cattle Carrying the Rob(1;29) Robertsonian Translocation? 151
Alicia Postiglioni, Rody Artigas, Andrés Iriarte, Wanda Iriarte, Nicolás Grasso and Gonzalo Rincón

 8 Epigenetic Defects Related Reproductive Technologies: Large Offspring Syndrome (LOS) 167
Makoto Nagai, Makiko Meguro-Horike and Shin-ichi Horike

 9 Aberrant DNA Methylation of Imprinted Loci in Male and Female Germ Cells of Infertile Couples 183
Takahiro Arima, Hiroaki Okae, Hitoshi Hiura, Naoko Miyauchi, Fumi Sato, Akiko Sato
and Chika Hayashi

 10 DNA Methylation and Trinucleotide Repeat Expansion Diseases 193
Mark A. Pook


Part 3 of the textbook : Methylation Changes and Cancer .

 
11 Investigating the Role DNA Methylations Plays in Developing Hepatocellular Carcinoma Associated with Tyrosinemia Type 1 Using the Comet Assay 211
Johannes F. Wentzel and Pieter J. Pretorius

 12 DNA Methylation and Histone Deacetylation: Interplay and Combined Therapy in Cancer 227
Yi Qiu, Daniel Shabashvili, Xuehui Li, Priya K. Gopalan,
Min Chen and Maria Zajac-Kaye

 13 Effects of Dietary Nutrients on DNA Methylation and Imprinting 289
Ali A. Alshatwi and Gowhar Shafi

 14 Epigenetic Alteration of Receptor Tyrosine Kinases in Cancer 303
Anica Dricu, Stefana Oana Purcaru, Raluca Budiu, Roxana Ola, Daniela Elise Tache, Anda Vlad

 15 The Importance of Aberrant DNA Methylation in Cancer 331
Koraljka Gall Trošelj, Renata Novak Kujundžić and Ivana Grbeša

 16 DNA Methylation in Acute Leukemia 359
Kristen H. Taylor and Michael X. Wang .




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