Epigenetics: A Reference Manual
"a key information resource" (EpiGenie)
"an outstanding resource" (Quart. Rev. Biol.)
Caister Academic Press
Jeffrey M. Craig and Nicholas C. Wong
Developmental Epigenetics Group, Murdoch Children's Research Institute, Victoria, Australia
xii + 450
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Epigenetics is the study of changes in gene expression caused by mechanisms other than changes in the DNA sequence. Epigenetics is a rapidly advancing field with an increasing impact on biological and medical research.
The editors of this book have assembled top-quality scientists from diverse fields of epigenetics to produce a major new volume. Comprehensive and cutting-edge, the 26 chapters in this book constitute a key reference manual for everyone involved in epigenetics, DNA methylation, cancer epigenetics and related fields. Topics include: early life environment, DNA methylation and behavior, histone acetyltransferase biology, transgenerational epigenetic inheritance, mammalian X inactivation, epigenetic memory in plants, polycomb-group regulation, centromeres and telomeres, DNA sequence contribution to nucleosome distribution, macrosatellite epigenetics, histones, cell-fate specification and reprogramming, DNA methylation in cancer, variant histone H2A and cancer development, RNA modification, paramutation in plants, DNMT3L dependent methylation during gametogenesis, non-coding RNA, bisulphite-enabled technologies, rapid analysis of DNA methylation, microarray mapping, DNA methylation profiling, ChIP-sequencing, genome-wide DNA methylation analysis, and epigenetics in maize. In addition there are useful chapters on bioinformatics in epigenomics, online resources and tools for epigeneticists, and educational resources for epigenetics.
This up-to-date reference manual is an essential book for those working in the field and for scientists in other disciplines it represents a major information resource on the fascinating and fast-moving field of epigenetics.
"essential to anyone working in epigenetics or related fields. The authors for each of the 26 chapters comprise an all-star cast of leaders in epigenetics research ... a key information resource on the intriguing and evolving world of epigenetics. Our only complaint? That it's not pocket-sized and waterproof, so that we can carry it with us everywhere." from EpiGenie (2011)
"Overall, the book provides a good overview of the major molecular, developmental, and technical elements of epigenetics ... it will be a good resource for both experts and nonexperts interested in the area of epigenetics ... an outstanding resource for any academic library." from Quart. Rev. Biol. (2013) 88: 351-352.
Table of contents
Section I. Introduction to Epigenetics and Epigenetic Methods
1. Early Life Environment, DNA Methylation and Behavior
The DNA molecule contains within its chemical structure two layers of information. The DNA sequence that bears the ancestral genetic information and the pattern of distribution of covalently bound methyl groups to cytosines in DNA. While the genetic information is similar in all tissues in the individual, the pattern of distribution of methylation across the genome is cell-type specific. DNA methylation is an important regulator of gene function. Recent data that will be discussed here that supports the hypothesis that DNA methylation is a reversible biological signal. This expands the potential role of DNA methylation beyond embryogenesis to other time-points in life and to post mitotic tissues such as the brain. DNA methylation is proposed to act as a genomic response to both physical and social signals from the environment at different time points in life and to serve as a genomic memory of these exposures at different time scales, stably altering gene expression programming and thus modulating the physical and behavioral phenotypes to respond to these environments. It is hypothesized that DNA methylation provides within the structure of the DNA a dynamic interface between the changing world around us and the relatively fixed and stable genome.
2. Concepts in Histone Acetyltransferase Biology
Anne K. Voss and Tim Thomas
A histone (H3-H4)2 tetramer flanked by two H2A-H2B heterodimers form the core protein structure, around which DNA is wrapped. DNA and the histone octamer together form the smallest chromatin particle, the nucleosome. How intimately the DNA associates with the core histones and how tightly the nucleosomes are packed with each other is determined by a key post-translational modification of the histone proteins, namely acetylation. Histone acetylation was first discovered in the early 1960s. After a dearth of progress, due to technical limitations, our knowledge of histone acetylation has exploded in the last fifteen years. Enzymes that catalyse acetylation of histones, the histone acetyltransferases, have been discovered, proteins associated with these have been identified and their preferences for specific histone residues have been determined. Importantly, we are gaining a better understanding of the relevance of histone acetylation in health and disease through the discovery of genetic mutations underlying human diseases in loci encoding histone acetyltransferases (HATs) and through examination of mouse strains deficient in specific histone acetyltransferases. Here we discuss the principles of histone acetyltransferase biology.
3. Murine Models of Transgenerational Epigenetic Inheritance
Jennifer E. Cropley and Catherine M. Suter
Epigenetic states are faithfully inherited through mitotic cell division, but are generally cleared and reset on passage through the mammalian germline. But this clearing of epigenetic marks is not always complete, leading to transgenerational inheritance of epigenotype. Transgenerational epigenetic inheritance has been demonstrated in several organisms, including mammals, and has been most comprehensively studied in mouse strains carrying variants of the agouti (Avy) and axin (AxinFu) alleles. The most prominent feature of transgenerational epigenetic inheritance is its non-Mendelian nature: not all offspring that inherit the genetic locus also inherit the parental epigenetic state. Transgenerational epigenetic inheritance is emerging as an important facet of mammalian biology. It may underlie the etiology of human diseases that display complex patterns of inheritance, including diabetes, mental illnesses and autoimmune diseases. As variable epigenetic states can be inherited on an invariant genotype, epigenetic variation may provide a substrate for Darwinian selection that is independent of genetic variation.
4. The Molecular Mechanisms of Mammalian X Inactivation
Marnie E. Blewitt and Linden J. Gearing
X chromosome inactivation is the method of dosage compensation that has evolved to equalise expression of X-linked genes between female (XX) and male (XY) mammals. In somatic cells only one X chromosome is active; the second X in female cells is silenced early during embryonic development, a process that involves the co-ordination of multiple levels of epigenetic regulation to ensure stable chromosome-wide silencing. In this chapter we shall focus on the molecular mechanisms involved in X chromosome inactivation, discuss how the epigenetic marks are believed to elicit stable transcriptional silencing, and why X inactivation represents an excellent model system for studying epigenetic regulation in mammals.
5. Epigenetic Memory in Plants: Polycomb-group Regulation of Responses to Low Temperature
Sandra N. Oliver and E. Jean Finnegan
Polycomb-group (PcG) complexes are essential regulators of plant development. These multiprotein complexes repress gene expression by establishing and maintaining trimethylation of lysine 27 at histone H3, a modification that is associated with repressive chromatin. Recent studies have indicated that plant PcG complexes regulate key genes involved in responses to low temperature. Vernalization is a long-term response to low temperatures whereby plants coordinate their seasonal flowering to occur after winter. In contrast, acclimation of plants to low temperatures, a key step in the establishment of frost tolerance, involves rapid activation of cold-acclimation genes. In this chapter, we describe the dynamics of PcG-mediated gene regulation underlying these two important agronomic traits that are triggered by low temperatures.
6. Centromeres and Telomeres
Emma L. Northrop and Lee H. Wong
In eukaryotes, each chromosome has one centromere and its ends are protected by telomeres. The centromere is a specialized chromosomal locus that directs kinetochore assembly and provides the site for microtubule attachment, allowing accurate chromosome segregation during cell division. Despite the critical role centromeres play, centromeric DNA sequences are highly variable and not conserved between species. Increasing evidence, including the discovery of functional neocentromeres, suggests that centromere identity and function is epigenetically defined through the formation of a specialised chromatin structure. This chapter reviews recent studies addressing the structural and functional characterisation of centromere chromatin, its assembly and propagation during cell division. Telomeres are specialized nucleoprotein complexes that protect the chromosome ends from degradation. In recent years, it has become increasingly clear that heterochromatic marks at telomeres act as negative epigenetic regulators of telomere elongation, repress recombination events at the telomere and are critical for maintaining telomere structural integrity. Recent research reporting telomeres being transcribed by RNA polymerase II to give rise to TERRA RNA, open up an additional level of regulation at the telomere. This chapter will discuss the links between the epigenetic status of telomeres, telomere function and telomere-length regulation, and the implications on cellular reprogramming, aging and cancer.
7. DNA Sequence Contribution to Nucleosome Distribution
Justin A. Fincher and Jonathan H. Dennis
DNA in eukaryotes is efficiently and compactly organized into chromatin, the fundamental subunit of which is the nucleosome: approximately 150 bp of DNA spooled 1.65 times around a histone octamer. The location and density of nucleosomes play a role in regulating nuclear processes including transcription, replication, recombination, and repair. Mechanisms acting in trans, like ATP-dependent remodelers and cellular memory complexes, as well as in cis features intrinsic to the DNA sequence itself regulate the location and density of nucleosomes. Here, we review the three cis acting DNA sequence features that affect the distribution of nucleosomes: (1) two frameworks defining the relationship between the histone octamer and the underlying DNA sequence (nucleosome occupancy and nucleosome position, then statistical positioning and a nucleosome positioning code), (2) the organization of DNA into the nucleosome core particle, and (3) specific DNA sequence features and DNA templates that promote or inhibit the formation of nucleosomes. We close by describing three computational algorithms trained on DNA sequence that have been used to predict nucleosome position and density. In summary, we hope to draw attention to multiple aspects of DNA sequence that specify organization of sequence into nucleosomes and influence the distribution of nucleosomes in eukaryotic genomes.
8. Macrosatellite Epigenetics
Brian P. Chadwick
The recent completion of several mammalian genome sequences makes obvious that we share a near-identical collection of genes. What defines us as human must therefore be encoded within regions of the genome where we differ, providing an added level of complexity that probably influences the spatial and temporal expression of genes. Most DNA sequence variation occurs within the repetitive DNA, once called 'Junk DNA' that accounts for at least half of the human genome, and evidence is mounting for its important role in genome function. Although some repeat elements are conserved to some extent between mammals, their precise copy number and genomic location typically are not. In addition, some repeats are not conserved, including the large tandem repeats. This chapter focuses on two large tandem arrays in the human genome that can adopt quite different chromatin configurations as a result of epigenetic changes; one as a direct consequence of X chromosome inactivation and the other in the context of disease susceptibility. Both cases highlight how alternate packaging of these unusual DNA sequences probably results in differing functions. In each instance, common denominators are the acquisition of the epigenetic organizer protein CTCF and a distinct change in transcripts originating from the array.
9. Histones: Dosage and Degradation
Rakesh Kumar Singh, Johanna Paik and Akash Gunjan
In eukaryotes, the genetic material in the form of DNA is wrapped around histone proteins to form nucleoprotein filaments called chromatin. Histones help package the DNA to fit it inside the nucleus of each cell, which in turn regulates access to the genetic information contained within the DNA. Hence, all DNA transactions are likely to be affected by histone metabolism. Eukaryotes carry multiple histones genes that can potentially generate enormous quantities of histone proteins. When present in excess, the positively charged histones can potentially "stick" non-specifically to the negatively charged DNA and adversely affect processes that require access to DNA. Not surprisingly, aberrant histone stoichiometry, chromatin assembly or chromatin structure lead to genomic instability, which is characterized by the increased rate of acquisition of alterations in the genome and is associated with deleterious human conditions such as cancer and aging. Hence, histone synthesis is coupled to ongoing DNA replication and is regulated transcriptionally and posttranscriptionally. To further avoid the deleterious consequences of excess histones, a posttranslational regulatory mechanism was described recently whereby excess histones are targeted for degradation by the ubiquitin-proteasome system. In this chapter, we discuss the causes and consequences of excess histone accumulation, as well as the strategies that cells have evolved to deal with them.
10. The Epigenetic Basis of Cell-Fate Specification and Reprogramming
Cell-fate specification and stem-cell renewal are fundamental processes in the development of multicellular organisms. In both animals and plants, a key role for transcription factors in these processes has been established, but an accumulating body of evidence indicates that epigenetic regulation also plays a critical role. Once regarded as stable marks, all epigenetic modifications, including DNA and histone methylation, are now known to be reversible, and a cohort of enzymes that add or erase epigenetic marks has been identified. Throughout the life of an organism, the epigenome is dynamically modified, leading in turn to transcriptional changes and ultimately cell-fate specification. Here, I review the recent literature that has shaped this view. Plants are unique among complex organisms in having the ability to generate a whole new organism from a single differentiated cell. How plant cells retain this amazing capability while maintaining their cell identity is a mystery. I introduce a model system for study of cell-fate specification, stem-cell renewal, and reprogramming.
11. DNA Methylation Changes in Cancer
Samson Mani and Zdenko Herceg
DNA methylation is an important regulator of gene transcription and a large body of evidence has demonstrated that aberrant DNA methylation is associated with unscheduled gene silencing, and the genes with high levels of 5-methylcytosine in their promoter region are transcriptionally silent. DNA methylation is essential during embryonic development, and in somatic cells, patterns of DNA methylation are generally transmitted to daughter cells with a high fidelity. Aberrant DNA methylation patterns have been associated with a large number of human malignancies and found in two distinct forms: hypermethylation and hypomethylation compared to normal tissue. Hypermethylation is one of the major epigenetic modifications that repress transcription via promoter region of tumour suppressor genes. Hypermethylation typically occurs at CpG islands in the promoter region and is associated with gene inactivation. Global hypomethylation has also been implicated in the development and progression of cancer through different mechanisms. This chapter will focus on DNA methylation as the major epigenetic mechanism involved in normal biological processes and abnormal events leading to cancer development. It will also focus on the interaction between DNA methylation and other epigenetic mechanisms.
12. Variant Histones H2A and Cancer Development
The histone variants of the H2A family are highly conserved in mammals, playing critical roles in regulating many nuclear processes by altering chromatin structure. One of the key H2A variants, H2A.X, marks DNA damage, facilitating the recruitment of DNA repair proteins to restore genomic integrity. Another variant, H2A.Z, plays an important role in both gene activation and repression. A high level of H2A.Z expression is ubiquitously detected in many cancers and is significantly associated with cellular proliferation and genomic instability. This review summarizes the current understanding of these variants and their functions, as well as their links to cancer development. Furthermore, the significance of dysfunction of these variants is highlighted with respect to their potential as biomarkers and as new targets for anticancer therapy.
13. 5-methylcytosine As a Modification in RNA
Jeffrey E. Squires and Thomas Preiss
A wealth of nucleobase and ribose modifications have been identified in multiple types of RNA including tRNAs, rRNAs, mRNAs, and small regulatory RNAs. Among them, 5-methylcytosine (m5C) has been detected in rRNAs, tRNAs, and early reports have indicated its presence in mRNAs. Well established as an epigenetic mark in DNA, the prevalence and function of m5C in RNA is either incompletely explored (tRNA, rRNA) or virtually unknown (mRNA, other noncoding RNA). Two eukaryotic m5C RNA methyltransferases have been identified; however, their substrate specificity and biological roles are incompletely understood. With recent advances in bisulfite sequencing of RNA, comprehensive analyses to determine the occurrence and functions of m5C in the transcriptome now appear feasible. In this chapter, we summarise the current knowledge in this field, focussing primarily on eukaryotic transcriptomes.
14. Paramutation in Plants
Mario A. Arteaga-Vazquez and Ana E. Dorantes-Acosta
Paramutation is a fascinating phenomenon in which epigenetic information can be transmitted through trans-interactions between one allele of a gene to another allele or between homologous DNA sequences that establishes a state of gene expression that is heritable for generations. Paramutation was discovered in maize and similar phenomena have been described in other plants, fungi and animals. In this chapter, we describe several classic plant paramutation systems and discuss recent advances that implicate a role for RNA and a number of components of an RNA-based transcriptional silencing pathway on paramutation.
15. Lessons from DNMT3L Dependent Methylation During Gametogenesis
Sarah A. Kinkel and Hamish S. Scott
DNMT3L (DNA methyltransferase 3 like) is member of the DNA methyltransferase family of enzymes responsible for the methylation of CpG dinucleotides. Biochemical studies have revealed that while DNMT3L lacks DNA methyltransferase activity, it can bind to and stimulate the activity of de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3L has also been shown to interact directly with chromatin via its plant homeodomain (PHD)-like zinc finger domain. Studies in Dnmt3L-deficient mice have revealed that DNMT3L is essential for establishing correct methylation patterns at RetroTransposable Elements (RTE), unique loci and parentally imprinted genes in germ cells, and mice without DNMT3L are rendered infertile. Female Dnmt3L-/- mice have apparently normal meiosis but in male Dnmt3L-/- germ cells there is asynapsis of chromosomes, and "meiotic catastrophe". Dnmt3L was among the first mammalian genes shown to have a paternal effect, where the genotype of the father (Dnmt3L+/-) affects sex chromosome aneuploidy in adult and embryonic offspring. This chapter will discuss the role of DNMT3L in establishing DNA methylation patterns during gametogenesis, as well as the proven and potential consequences of DNMT3L-deficiency to fertility and somatic and germline genetic disease in light of the increasing evidence that epigenetic reprogramming is a dose sensitive and partially stochastic process.
16. Non-Coding RNA: an Overview
Alka Saxena and Piero Carninci
In the past decade, we have become acquainted with an entire new world of fine regulatory control within cells governed by non-coding RNAs. Although we have not completely explored this world, we know from a few well studied examples that not only gene dosage but protein function also, is fine tuned by non-coding RNAs. It appears that proper cell function is largely dependent on non-coding RNAs, many of which were invisible to us until the advent of high throughput sequencing and tiling array technology. The realization, that transcripts with no open reading frames are biologically active molecules with multiple functions including regulation of the expression of coding RNA, shifts the power from proteins to non-coding RNAs as key modulators of cellular function. In this review, we discuss the various classes of non coding RNAs and the mechanisms employed by them to achieve this status, with a particular focus on their ability to induce epigenetic modifications.
Section II. Epigenetic Techniques
17. Bisulphite-enabled Technologies
A large variety of methods to measure DNA methylation have been developed and used extensively over the last twenty years. These have been based on selective restriction digestion of methylated DNA, the capture of methylated DNA by methyl binding proteins or antibodies, or bisulphite conversion of DNA. However, all restriction enzyme based methods are dependent on available restriction sites for methylation-specific restriction enzymes and therefore cannot be used to analyse every CpG site in the genome. Although immunoprecipitation methods are not sequence specific, they are unable to provide methylation data at a single-base resolution. Therefore, both of these approaches are limited in their applicability. On the other hand, bisulphite conversion based methods allow methylation studies directed to any CpG site in the genome. Sodium bisulphite treatment of DNA converts all unmethylated cytosines into uracil while methylated cytosines remain unchanged, thus transferring an epigenetic difference into a measureable genetic difference. A variety of downstream methods such as Polymerase Chain Reaction (PCR), sequencing, Single Nucleotide Polymorphism (SNP) genotyping and mass spectrometry can be coupled with bisulphite conversion. This chapter provides an overview of some of these methods, concentrating on bisulphite sequencing, methylation-specific PCR, pyrosequencing, MassARRAY EpiTYPER and Infinium HumanMethylation27 BeadChip. Considerations for assay selection and detailed protocols for each method are presented in the end of this chapter.
18. Methylation-sensitive High Resolution Melting for the Rapid Analysis of DNA Methylation
Thomas Mikeska and Alexander Dobrovic
Methylation-sensitive high resolution melting (MS-HRM) is an inexpensive and robust closed tube screening methodology that enables rapid analysis of locus specific DNA methylation for multiple samples. MS-HRM is based on the differential melting behaviour of PCR amplification products derived from methylated and unmethylated templates after bisulfite treatment. The melting profiles of an unknown sample are compared to the melting profiles of standards with known DNA methylation levels. MS-HRM has the advantage of allowing ready distinction between homogenous and heterogeneous DNA methylation. Estimation of DNA methylation to quite low levels in a semi-quantitative manner is possible for homogeneously methylated templates where all the CpG sites are methylated. However for heterogeneous methylation, the formation of multiple heteroduplexes makes quantitation difficult. Digital MS-HRM utilises limiting dilution to amplify single templates enabling DNA methylation analysis at a single allele resolution and enables the quantitative analysis of both homogenous and heterogeneous methylation. The PCR products either generated by MS-HRM or digital MS-HRM can subsequently undergo Sanger DNA sequencing or pyrosequencing to investigate DNA methylation at individual CpG positions.
19. Microarray Mapping of Nucleosome Position
Brian Spetman, Sarah Lueking, Brooke Roberts and Jonathan H. Dennis
The location and density of nucleosomes in the eukaryotic genome plays a role in regulating nuclear processes including transcription, replication, recombination, and repair. Microarray mapping of nucleosomally protected DNA has emerged as a powerful, cost-effective, high-throughput method to analyze the relationship between nucleosome position and genomic regulation. In this chapter we discuss experimental considerations such as sample preparation and microarray design. In addition, two procedures are detailed: (1) Formaldehyde Crosslink and Harvest Cells, Isolate Nuclei, and MNase cut chromatin, and (2) Isolation of mononucleosomally protected DNA and fluorescent labeling of DNA for microarray hybridization. With the information specified in this chapter, most any laboratory equipped for molecular biology with institutional or commercial access to microarray facilities should be should be able to map nucleosome position and occupancy.
20. Enzymatic Approaches for Genome DNA Methylation Profiling
Benjamin Chanrion, Yurong Xin and Fatemeh Haghighi
DNA methylation plays an essential role in normal human development, where abnormalities in proper establishment and maintenance of DNA methylation patterns result in human disease. Many experimental approaches have been developed for assaying DNA methylation patterns, including enzymatic-based approaches. In this chapter, we highlight some of these approaches and describe their relative advantages and disadvantages. We also describe advances in microarray and sequencing technologies that have improved resolution of enzymatic-based methods, providing expanded coverage of CpG dinucleotides throughout the genome. These approaches are important tools in characterizing the role of DNA methylation in genome organization and function.
Sebastian Lunke and Assam El-Osta
With the advances in traditional genetics failing to provide causal genes for many complex diseases, the focus of research is shifting towards determining the importance of gene-environment interactions, more specifically epigenetic regulation. Paramount to answering this question is the knowledge of which transcription factors bind to what sequence, as well as a detailed understanding of how the transcriptional state of a genetic sequence is epigenetically distinguished. The chromatin immuno-precipitation (ChIP) strategy has proven to be a powerful tool to investigate these mechanisms, but has been limited for a long time to single locus analysis. The recent emergence of next-generation sequencing (NGS) technology however has revolutionized the field of epigenomics and for the first time enabled unbiased genome-wide analysis of ChIPed DNA. Here we provide a detailed discussion and protocol on how to best perform ChIP for NGS analysis.
22. Genome-wide DNA Methylation Analysis
Marcel W. Coolen and Susan J. Clark
Over the past decades it has become ever more apparent that understanding the genome did not stop with unravelling the genetic code. Regulatory mechanisms are needed to determine which parts of the genome are active or inactive, and to form a memory system that can be passed on over multiple cell divisions for proper functioning of the cell. These mechanisms underpinning heritable gene regulation are encapsulated by the term "epigenetics" and include histone modifications, miRNA and non-coding RNA expression, and methylation of cytosine residues in DNA. In this review, we compare the various methods that can be used to analyse DNA methylation patterns throughout the genome, and discuss their advantages and disadvantages. In addition, we present a detailed protocol for genome-wide DNA methylation analysis based on the capture of methylated DNA using a methyl-CpG binding domain-based (MBD) protein combined with second generation sequencing.
Section III. Epigenetics Reference Manual
23. Bioinformatics Analysis of Epigenomic Methylation Patterns in the Era of Massively Parallel Sequencing
Mark D. Robinson, Bryan Beresford-Smith, Anthony Kaspi and I. Haviv
Since biological phenotype and differentiation is regulated partially through CpG DNA methylation, and this mark is relatively easy to measure, genome-wide profiling of methylation landscape is a popular tool in epigenetic research. The burden then falls on bioinformatics to provide normalization, quality control, and interpretation, while adopting to the vast number of versatile methods to interrogate methylation profiles. While creating a relational report of the results from either of these methods is critical for data to cross over from lab to lab, and from research to diagnostic and translation purposes, the methods are each introducing their unique bias to the data. Ideally, one would hope all labs would adopt a single method, but since each method offers a unique advantage, such as price, sensitivity, or confidence, one has to overcome the disparity hurdle via bioinformatic tools. Thus identifying the methodological biases of each technique, and the way to compensate for those in the process of generating a universal CpG methylation prediction on a genome region is the ultimate goal we are describing here. Follow up of CpG methylation with other read outs, such as impact on gene expression or coincidence with locations in the genome, where allelic variation is associated with the investigated phenotype, are also key to proper interpretation of the results.
24. Genetic Resources for the Study of Epigenetic Gene Regulation in Maize
Andre Irsigler and Karen M. McGinnis
Maize has served as an excellent model for the study of epigenetic gene regulation for the past several decades. The pioneering work of maize geneticists like Barbara McClintock, Alexander Brink, Marcus Rhoades, and others led to the observation of many fascinating phenomena that were later demonstrated to be epigenetically regulated events. Since these observations were made, a great deal of progress has been made in determining the underlying causes of the phenomena, and many of these examples of epigenetic gene regulation are currently being used to elucidate the mechanisms of epigenetic heritability in plants. Today, these phenomena and the mutants that impact them serve as resources for studying how DNA methylation, chromatin structure, and small RNAs act to influence paramutation, gene silencing, and parent-of-origin dependent dosage compensation. The key attributes and potential contributions of each resource are discussed in the context of understanding the mechanisms and significance of epigenetic gene regulation in large, complex genomes.
25. Online Resources and Tools for Epigeneticists
Nicholas C. Wong
Biological experiments are rapidly moving into the information age with the explosion of data generated from rapidly evolving technologies. Microarrays can interrogate many thousands to millions of loci within any one sample, while massively parallel sequencing platforms can essentially measure the entire genome. Keeping up with this rapid pace of data accumulation has required the development of online tools for the processing, analysis and annotation of data generated from large numbers of microarrays or next generation sequencing (NGS) experiments. I will cover a selected range of tools available to the biological researcher, from online discussion forums and blogs, to curated databases that store the data and associated annotations. I will then cover viewer tools that enable visualisation the annotations and finally review tools for assay design for follow up validation of NGS and microarray analyses. I will pay particular attention to DNA methylation and provide the reader with an insight into what is available online for the epigenetics researcher aiming to make sense of epigenomic data. As a disclaimer, this chapter is by no means a comprehensive list of available epigenetics resources, which are constantly being updated and expanded through the Internet and just a mouse click through Google away.
26. Educational Resources for Epigenetics
Yuk Jing Loke and Jeffrey M. Craig
Epigenetics can appear as an impenetrable subject; not just to those encountering it for the first time, but to those within the field too. However, epigenetics, like any subject can be made easier to understand using a combination of clear language, creative illustrations and even animations and film clips. This chapter aims to point readers of all experiences towards helpful and easy-to-read resources that educate about epigenetics. It is split into two main sections, the first aimed at a lay audience including teachers and high school students and the second, at graduate and postgraduate students and beyond. Each section contains summaries of published articles and web sites. The chapter ends with a short section on epigenetic societies and research networks and a summary table of resources. It is intended to provide a sample of some of the best short to medium length reviews on general topics within the field of epigenetics and while we cover a wide variety of themes, we apologise for any areas not covered. We cite the URLs of freely-available articles wherever possible, but many articles will require library access. We also urge readers to contact authors or publishers if they wish to distribute any of the articles for teaching purposes.
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(EAN: 9781904455882 9781912530533 Subjects: [molecular microbiology] [genomics] [bioinformatics] [molecular biology] [epigenetics] )