Epigenetics: Medicine & Health Science Books @ . Epigenetics 1st Edition. by Jorg Tost (Editor). Be the first to review this item. Jorg Tost, Director, Centre National de Genotypage CEA before becoming Director of Laboratory for Epigenetics and Environment at the Centre National de . This volume discusses technologies that analyze global DNA methylation contents, various NGS based methods for genome-wide DNA methylation.
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The field of epigenetics has gained great momentum in recent years and is now a rapidly advancing field of biological and medical research. Epigenetic changes play a key role in normal development as well as in disease. The editor of this book has assembled top-quality scientists from diverse fields of epigenetics to produce a major new volume on current epigenetics research. In this book the molecular mechanisms and biological processes in which epigenetic modifications play a primordial role are described in detail.
The first seven chapters describe the different biological mechanisms of the epigenetic machinery including: The following chapters cover the epigenetic systems of plants, the epigenetic profile of embryonic stem cells, cell differentiation, imprinting marks, and random X chromosome inactivation. Further chapters deal with epigenetics in relation to cancers, premature aging, longevity and the developmental origins of disease.
The final chapter, describes the fascinating potential transfer of epigenetic information across generations. This up-to-date volume is a major resource for those working in the field and will stimulate readers of all levels to dive into the fascinating and fast moving field of epigenetics. The text is clear and concise and all reports include accurate data and figures. It is highly recommended for personal and institutional purchase.
One of the greatest strengths of this edited work is the variety of researchers contributing to the dynamics of the work’s comprehensive nature It will quite effectively cater to the needs of molecular biologists, molecular geneticists, cell and molecular biologists, animal, plant, and crop geneticists, synthetic biologists, biotechnologists, and researchers involved with the fields of stem cell and molecular aspects of cancer research.
Books Site Journal Backlist Gateway. In mammals, cytosine methylation at CpG positions of the DNA sequence is one of the hallmarks of epigenetic gene silencing. During evolution, CpG rich regions, so-called CpG islands, have been established as prominent features of promoter regions of genes.
Whereas most regions of the genome are constantly methylated these elements are mainly kept free of methylation thereby facilitating the establishment of an open chromatin structure and of initiation of transcription.
Besides its role in the regulation of genes, DNA methylation silences repetitive elements and appears to be important for the stability of the mammalian genome. Thus, DNA methylation influences the functional integrity of mammalian genome by shaping its overall structure and leaving its marks in the genomic DNA sequence during evolution.
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The epigenetic modification of DNA with 5-methylcytosine is an important regulatory event involved in chromatin structure, genomic imprinting, inactivation of the X chromosome, transcription, and retrotransposon silencing. This modification is catalyzed and maintained by the DNA methyltransferases and is interpreted by the methyl-CpG binding proteins. DNA methyltransferases are not limited to catalyzing DNA methylation, but also take part in the regulation of gene expression through interactions with other proteins that repress transcription and modify chromatin structure.
The use of mouse models, as well as human diseases resulting from deficiencies in the methylation machinery, have been integral parts of understanding the role of these proteins in development and cellular homeostasis.
More and more studies are reporting additional roles within the cell beyond their DNA methyltransferase and methyl-CpG binding properties.
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There is at this point, though, only limited understanding of how these enzymes and proteins are targeted to specific genomic regions. The function of these enzymes, as well as their interactions with other cellular proteins and each other, will be discussed along with the diseases attributed to aberrations in the DNA methylation machinery.
DNA methylation has experienced a large increase in interest in the last years and the analysis of DNA methylation either on a genome-wide or gene-specific scale has come to center stage for many biological and medical questions. Realizing the importance of epigenetic changes in development and disease and the potential of DNA methylation as reliable biomarker, a large variety of techniques for the study of DNA methylation has been developed in the last years.
No single method has emerged as the “gold” standard unifying quantitative accuracy and high sensitivity or possibilities for whole-genome analysis and precise investigation of individual CpG positions.
In this review I summarize most of the developed methods that allow the discovery of a region with DNA methylation changes on a genome-wide scale, the methods to rapidly validate a region of interest, the available possibilities to fine-type the CpG positions in an identified target region and finally technologies that permit the sensitive detection of specific DNA methylation patterns in biological fluids.
The choice of the method mainly depends on the desired application, the required sensitivity, the biological material and many studies will require a combination fost several methods. Histone Modifications and Epigenetics. Sims, Tanya Magazinnik, Sabrina I. Houston, Shumin Wu and Judd C. While the DNA sequence in all cells of an organism is identical, each different cell type is largely defined by the specific sets of genes that are expressed and repressed in that particular cell type.
Therefore, cell fate and identity are generally governed by gene expression patterns. In the last decade it has become increasingly clear that the DNA-associated histone proteins play an important, yet enigmatic, joorg in gene regulation within the mammalian genome.
In this chapter we discuss the various covalent chemical modifications of the histones and, by using histone methylation as a model, we illustrate the current paradigm of how histone modifications directly participate in various DNA-templated processes such as transcription. Histone Variants and Nucleosome Occupancy. The modification of chromatin structure is proving to be an important component of many processes involving DNA.
The three recognized mechanisms for modifying chromatin are ATP dependent chromatin remodeling, covalent modification of histones and incorporation of histone sequence variants. Histone variants discussed in this chapter include H3. Bbd, H1 variants and testis tos variants. Table 1 summarizes functions associated with these variants. This chapter also deals with the role of the above-mentioned chromatin-modifying mechanisms and DNA sequences in defining the range of nucleosome occupancy levels found throughout the eukaryotic genome.
Molecular Mechanisms of Polycomb Silencing. Polycomb and Trithorax group proteins have long been known as important epigenetic regulators of homeotic genes.
Recent advances in genome-wide mapping techniques have uncovered their broad role in cell differentiation, which is exerted through the direct control of hundreds of transcription factors as well as important signaling proteins and morphogens. Polycomb silencing, originally believed to result from stable packaging of chromatin is now viewed as dynamic process intimately dependent on histone modifications and balanced by antagonistic action of Trithorax proteins.
These elements are thought to contain a collection of binding sites for sequence-specific DNA binding proteins that assemble PcG complexes.
PREs serve epigeetics binding hubs where Polycomb proteins remain localized but loop over to interact with the promoters and other parts of target genes. Recent studies have revealed a surprisingly large number of RNAs transcribed in eukaryotic cells.
Although the ncRNAs that have so far been characterized represent only the tip of iceberg, it is becoming increasingly evident that ncRNAs are functionally involved in many biological processes, such as proliferation, differentiation and development. MiRNAs and their targets appear to form complex regulatory networks. In addition, miRNAs cooperate with transcription factors to control gene expression.
The properties of gene regulatory networks tosg as feedback loops generated by the combinatorial action of TFs and miRNAs, which facilitate both sustained response and quick transition to stimulation, are beginning to be understood. In this chapter, current knowledge of the epigenetic systems of plants is compared to those discovered in other eukaryotes.
A broad overview of the components of epigenetic systems in plants will be made – covering small RNA pathways, DNA methylation and chromatin – and comparisons made to other organisms in respect to their regulation, organisation and function. In this way, both conserved elements and novel plant-specific innovations will be discussed. A particular theme is the comparative richness of the plant epigenetic machinery in small gene families, such as diversity in Argonaute epigeneticd Polycomb-group proteins.
The reason for the greater epigenetic complexity in plants is not simply their multicellular development but also their need to cope with an ever-changing environment due to their sessile lifestyle. Not only does this necessitate exceptional flexibility in gene expression and developmental programmes but also defence against invasive genomes such as viruses.
All of these challenges are met by the various parts of their epigenetic systems. Embryonic Stem Cell Epigenetics.
Stem cells can both self-renew and produce multiple cell types. Unlike adult stem cells, which can give rise to either one differentiated cell type unipotent or multiple cell types multipotentembryonic stem ES cells are pluripotent, meaning they can contribute to any tissue type in the body.
Each cell type, be it pluripotent or terminally differentiated, is defined by the genes that it expresses and represses, and control tosf gene expression is fundamental to the process of differentiation.
A number of epigenetic processes, including histone modification, DNA methylation and chromatin remodelling, are vital for the ability of ES cells to differentiate correctly.
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The ES cell epigenome possesses certain features that are unique to these cell types and are involved in the regulation of pluripotency. It has been suggested that this unique epigenetic profile allows ES cells to both prevent transcription of genes associated with differentiation, but also to allow transcription should the correct developmental signals jrog received. Understanding transcriptional control in pluripotent and differentiating cells will be vitally important for ES cells fulfil their potential for regenerative medicine.
The Biology of Genomic Imprinting. It takes place at a small subset of genes termed imprinted genes, where the epigenetic marking dictates parental allele-specific imprinted gene expression in somatic tissues. These marks take form as differential DNA methylation, at specialized sequence elements called ‘imprinting control regions’ ICRs.
Translating these methylation imprints into the appropriate patterns of gene expression is crucial for the development and growth of the embryo, and for postnatal well-being.
This review focuses on the biology of genomic imprinting in mammals, discussed in two parts. The first part elaborates the ‘reading’ of the imprints; i. Included is a discussion on the related process, which assures the maintenance of these imprints in somatic tissues. Examples of various reading mechanisms are presented including the blocking of long-range promoter-enhancer interactions and the involvement of non-coding RNAs in chromatin repression.
The second part addresses the mechanism involved in assuring the re-establishment of new imprints in the next generation. It discusses the processes which erase and re-establish the imprints in the male and female germ lines. X inactivation in mammals achieves dosage compensation of X chromosomal genes between XX females and XY males. One of the two female X chromosomes becomes transcriptionally inactivated early in development, such that in both male and female embryos one X chromosome is active.
A mechanism for counting and choice ensures that precisely one X chromosome remains active and all super numerous Xs are inactivated. X chromosome counting and regulation of choice are mediated by a single locus on the X – the X inactivation center Xic.
Chromosome-wide inactivation is initiated by and crucially depends on the expression of the long non-protein-coding Xist RNA. Xist RNA is transcribed from the Xic on the future inactive X Xiattaches to Xi chromatin and accumulates over the chromosome triggering transcriptional silencing. Thus, Xist is a powerful epigenetic regulator that is able to inactivate an entire chromosome. Xist is essential for initiation of X inactivation but the Xi is maintained independent of Xist by other epigenetic mechanisms.
Therefore, X inactivation can be mechanistically separated into an initiation and a maintenance phase. The function of Xist RNA in initiation of silencing is strictly dependent on a particular cellular context. In differentiated cells Xist expression is not sufficient for initiating gene repression.
X inactivation is a multistep process that comprises an ordered series of chromatin modifications that occur in a developmentally regulated manner.
Recruitment of Polycomb group proteins PcGwhich are known to be required for maintaining the repression of Hox genes, to the Xi has been implicated in the transition from the initiation phase to the maintenance phase of X inactivation. Also factors with a role in chromatin and nuclear structure, such as scaffold attachment factor A Saf-A or the histone variant macroH2A, are recruited to the Xi and have been implicated in the stabilization of the inactive state.
X inactivation, thus, provides a model for developmentally regulated formation of silent chromatin domains as similar mechanisms might regulate gene expression in a more general, albeit smaller, context. Genetic and epigenetic mechanisms contribute to the development of human tumors, yet the typical analysis of tumors is focused on only one or the other mechanism.
This approach has led to a biased, primarily genetic view of human tumorigenesis. Epigenetic alterations such as aberrant DNA methylation are mitotically heritable, sufficient to induce tumor formation, and can modify the incidence and tumor type in genetic models of cancer.