Download or read book Dynamic regulation of DNA methylation in human T cell biology written by Antonio Lentini and published by Linköping University Electronic Press. This book was released on 2019-03-19 with total page 65 pages. Available in PDF, EPUB and Kindle. Book excerpt: T helper cells play a central role in orchestrating immune responses in humans. Upon encountering a foreign antigen, T helper cells are activated followed by a differentiation process where the cells are specialised to help combating the infection. Dysregulation of T helper cell activation, differentiation and function has been implicated in numerous diseases, including autoimmunity and cancer. Whereas gene-regulatory networks help drive T-cell differentiation, acquisition of stable cell states require heritable epigenetic signals, such as DNA methylation. Indeed, the establishment of DNA methylation patterns is a key part of appropriate T-cell differentiation but how this is regulated over time remains unknown. Methylation can be directly attached to cytosine residues in DNA to form 5-methylcytosine (5mC) but the removal of DNA methylation requires multiple enzymatic reactions, commonly initiated by the conversion into 5-hydroxymethylcytosine (5hmC), thus creating a highly complex regulatory system. This thesis aimed to investigate how DNA methylation is dynamically regulated during T-cell differentiation. To this end, we employed large-scale profiling techniques combining gene expression as well as genome-wide 5mC and 5hmC measurements to construct a time-series model of epigenetic regulation of differentiation. This revealed that early T-cell activation was accompanied by extensive genome-wide deposition of 5hmC which resulted in demethylation upon proliferation. Early DNA methylation remodelling through 5hmC was not only indicative of demethylation events during T-cell differentiation but also marked changes persisting longterm in memory T-cell subsets. These results suggest that priming of epigenetic landscapes in T-cells is initiated during early activation events, preceding any establishment of a stable lineage, which are then maintained throughout the cells lifespan. The regions undergoing remodelling were also highly enriched for genetic variants in autoimmune diseases which we show to be functional through disruption of protein binding. These variants could potentially disrupt gene-regulatory networks and the establishment of epigenetic priming, highlighting the complex interplay between genetic and epigenetic layers. In the course of this work, we discovered that a commonly used technique to study genome-wide DNA modifications, DNA immunoprecipitation (DIP)-seq, had a false discovery rate between 50-99% depending on the modification and cell type being assayed. This represented inherent technical errors related to the use of antibodies resulting in off-target binding of repetitive sequences lacking any DNA modifications. These sequences are common in mammalian genomes making robust detection of rare DNA modifications very difficult due to the high background signals. However, offtarget binding could easily be controlled for using a non-specific antibody control which greatly improved data quality and biological insight of the data. Although future studies are advised to use alternative methods where available, error correction is an acceptable alternative which will help fuel new discoveries through the removal of extensive background signals. Taken together, this thesis shows how integrative use of high-resolution epigenomic data can be used to study complex biological systems over time as well as how these techniques can be systematically characterised to identify and correct errors resulting in improved detection.
Download or read book Dynamic Regulation and Functions of Locus specific DNA Methylation written by Yuelin Song (Ph. D.) and published by . This book was released on 2020 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt: The role and regulation of DNA methylation at various genetic elements have gathered tremendous interest over decades. The methylomes of many cell types have been described, revealing a dynamic and tissue-specific pattern of DNA methylation (tissue-specific differentially methylated regions, T-DMRs) in the distal regulatory elements, such as enhancers. The formation of T-DMRs still remain mysterious, however, one of their interesting features observed in mouse ES cells (mESCs) is the low-to-intermediate levels of average DNA methylation resulted from inter-cellular epigenetic heterogeneity. Given the transcriptional repressive role of DNA methylation at promoters, such non-zero levels of enhancer methylation is interesting to characterize. Prior to this thesis, a reporter for genomic DNA methylation (RGM) has been developed in the Jaenisch lab, when targeted into T-DMRs of interest, the surrounding locus-specific DNA methylation will be reported as on-and-off of fluorescent signals in single cells. We further modified RGM to investigate the regulation of DNA methylation at pluripotency super-enhancers Sox2 and MiR290 at single allele level in mESCs. We found that enhancer DNA methylation is surprisingly dynamic with two alleles independently being demethylated and methylated within days. Such dynamics is the basis of epigenetic and transcriptional heterogeneity and is coupled with changes in histone modifications and transcription factor binding. Furthermore, epigenetic heterogeneity was also observed in the developing preimplantation embryos. Our work provided a paradigm to functionally investigate locus-specific DNA methylation in heterogenous tissues in diseases and development. The regulation of locus-specific DNA methylation is highly context dependent and sensitive to the environment. Our understanding of how locus-specific DNA methylation is regulated in vivo is still restricted to a few genomic elements. The appendix of this thesis attempts to generate an animal model to expand the scope of research on DNA methylation to retroelement-associated metastable epialleles.
Download or read book Signaling Mechanisms Regulating T Cell Diversity and Function written by Jonathan Soboloff and published by CRC Press. This book was released on 2017-03-27 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.
Download or read book DNA Methylation Dynamics in the Functional Regulation of Human T Lymphocytes written by Lucia Vincenzetti and published by . This book was released on 2018 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thèse. Biologie. Médecine. 2018
Download or read book DNA Methylation and Complex Human Disease written by Michel Neidhart and published by Academic Press. This book was released on 2015-08-11 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. - Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity - Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field - Describes wholly new concepts, including the linking of metabolic pathways with epigenetics - Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases
Download or read book DNA Methyltransferases Role and Function written by Albert Jeltsch and published by Springer. This book was released on 2016-11-08 with total page 537 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA methyltransferases are important enzymes in a broad range of organisms. Dysfunction of DNA methyltransferases in humans leads to many severe diseases, including cancer. This book focuses on the biochemical properties of these enzymes, describing their structures and mechanisms in bacteria, humans and other species, including plants, and also explains the biological processes of reading of DNA methylation and DNA demethylation. It covers many emerging aspects of the biological roles of DNA methylation functioning as an essential epigenetic mark and describes the role of DNA methylation in diseases. Moreover, the book explains modern technologies, like targeted rewriting of DNA methylation by designed DNA methyltransferases, as well as technological applications of DNA methyltransferases in DNA labelling. Finally, the book summarizes recent methods for the analysis of DNA methylation in human DNA. Overall, this book represents a comprehensive state-of-the-art- work and is a must-have for advanced researchers in the field of DNA methylation and epigenetics.
Download or read book Genome scale Studies of Dynamic DNA Methylation in Mammalian Brain Cells written by Christopher Lee Keown and published by . This book was released on 2018 with total page 165 pages. Available in PDF, EPUB and Kindle. Book excerpt: Developmental processes, genes and environmental factors interact to produce changes in cognition and behavior over the lifespan of an individual. However, the underlying molecular genetic mechanisms that mediate these changes remain to be fully elucidated. DNA methylation is an epigenetic mechanism that defines cell identity and helps regulate gene expression. DNA methylation is dynamic over development and has been shown to mediate experience-dependent changes, including those resulting from learning and memory and early life adversity. Although methylation mainly occurs at genomic cytosines in the CG dinucleotide context, methylation at non-CG sites was recently found in brain tissue. Non-CG methylation is specifically enriched in neurons and accumulates during the early childhood stages of brain development. The biological impact of non-CG methylation in regulating gene expression and regulating cellular function, if any, remains unclear. A major challenge for addressing this question is the complexity and scale of the DNA methylation landscape, which includes nearly one billion cytosines throughout the genome that are potential sites of modification in every cell. Targeted studies of specific candidate genes and genomic loci do not elucidate the overall configuration of the cellular epigenome. Techniques for comprehensively mapping the genome-wide distribution of DNA methylation are powerful, but they require sophisticated new computational methods of analysis that can reliably distinguish and statistically validate epigenomic differences related to developmental and environmental factors. In this thesis we develop new approaches to comprehensively analyze DNA methylation throughout the genome and with single base resolution in order to better characterize the role of CG methylation and elucidate the potential role of CH methylation in mammalian brain cells. First, we consider the impact of enriched early life (peri-pubertal) experience on DNA methylation and gene expression in the dentate gyrus of the hippocampus. In addition to its role in experience-dependent gene regulation, DNA methylation also plays a key role in innate developmental processes, including female X chromosome inactivation. We provide the first allele-specific DNA methylomes from the active and inactive X chromosomes in female brain, and use comprehensive genomic analyses to gain insight into the functional relationship between allele-specific DNA methylation and transcription. These two studies provide new evidence of the dynamic changes in DNA methylation in whole brain tissue caused by environmental and innate developmental factors. However, they do not address the heterogeneity of brain cell types, a hallmark of mammalian brain organization. To address the role of DNA methylation in brain cell diversity, we develop computational methods to analyze data from a new assay that measures single cell methylomes. Using these data, we show that brain cell methylomes can be clustered and used to assess neuronal heterogeneity in the frontal cortex of mouse and human. Upon clustering cells, we are able to gain insight into the role of methylation in the establishment and maintenance of cellular identity in neuronal types. Overall, this thesis adds to the increasing evidence that DNA methylation is a cell type-specific, dynamic epigenomic modification of brain cells that is impacted by, and may in turn help to regulate, neuronal development and adaptation. In addition, this thesis provides new computational methods for analyzing large-scale, whole-genome DNA methylation data sets and demonstrates their use in uncovering new insights into the mammalian brain epigenome.
Download or read book Human Gametes and Preimplantation Embryos written by David K. Gardner and published by Springer Science & Business Media. This book was released on 2013-05-27 with total page 307 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, the advancing science and increasing availability of assisted reproduction have given new hope to infertile couples. However, the use of IVF and ART has also led to marked increases in the number of multiple-infant live births. This poses a public health concern, as these neonates have a higher rate of pre-term delivery, compromising their survival chances and increasing their risk of lifelong disability. By optimizing the selection of gametes and embryos with high probabilities of implantation, it is possible to reduce the number of embryos transferred and, by extension, the number of high-risk multiple gestations, while maintaining or increasing pregnancy rates. Human Gametes and Preimplantation Embryos: Assessment and Diagnosis provides a broad yet concise overview of established and developing methodologies for assessment of gamete and embryo viability in assisted reproduction. This book elucidates the best practices for precisely selecting viable specimens based on morphology and cleavage rate and covers the spectrum of emerging adjunctive technologies for predicting reproductive potential. The authors present their extensive knowledge of “omics” approaches (genomics, transcriptomics, proteomics, and metabolomics), with unbiased delineation of the associated advantages and potential pitfalls. This valuable clinical resource is well suited to infertility specialists, Ob/Gyn physicians, IVF laboratory technicians, and researchers in the fields of embryology and reproductive medicine.
Download or read book Epigenetics of Aging written by Trygve O. Tollefsbol and published by Springer Science & Business Media. This book was released on 2009-11-11 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have indicated that epigenetic processes may play a major role in both cellular and organismal aging. These epigenetic processes include not only DNA methylation and histone modifications, but also extend to many other epigenetic mediators such as the polycomb group proteins, chromosomal position effects, and noncoding RNA. The topics of this book range from fundamental changes in DNA methylation in aging to the most recent research on intervention into epigenetic modifications to modulate the aging process. The major topics of epigenetics and aging covered in this book are: 1) DNA methylation and histone modifications in aging; 2) Other epigenetic processes and aging; 3) Impact of epigenetics on aging; 4) Epigenetics of age-related diseases; 5) Epigenetic interventions and aging: and 6) Future directions in epigenetic aging research. The most studied of epigenetic processes, DNA methylation, has been associated with cellular aging and aging of organisms for many years. It is now apparent that both global and gene-specific alterations occur not only in DNA methylation during aging, but also in several histone alterations. Many epigenetic alterations can have an impact on aging processes such as stem cell aging, control of telomerase, modifications of telomeres, and epigenetic drift can impact the aging process as evident in the recent studies of aging monozygotic twins. Numerous age-related diseases are affected by epigenetic mechanisms. For example, recent studies have shown that DNA methylation is altered in Alzheimer’s disease and autoimmunity. Other prevalent diseases that have been associated with age-related epigenetic changes include cancer and diabetes. Paternal age and epigenetic changes appear to have an effect on schizophrenia and epigenetic silencing has been associated with several of the progeroid syndromes of premature aging. Moreover, the impact of dietary or drug intervention into epigenetic processes as they affect normal aging or age-related diseases is becoming increasingly feasible.
Download or read book Environmental Genomics written by C. Cristofre Martin and published by Springer Science & Business Media. This book was released on 2008-01-18 with total page 363 pages. Available in PDF, EPUB and Kindle. Book excerpt: Here is a manual for an environmental scientist who wishes to embrace genomics to answer environmental questions. The volume covers: gene expression profiling, whole genome and chromosome mutation detection, and methods to assay genome diversity and polymorphisms within a particular environment. This book provides a systematic framework for determining environmental impact and ensuring human health and the sustainability of natural populations.
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Epigenetics and Chromatin written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2008-09-10 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics refers to heritable patterns of gene expression which do not depend on alterations of genomic DNA sequence. This book provides a state-of-the-art account of a few selected hot spots by scientists at the edge in this extremely active field. It puts special emphasis on two main streams of research. One is the role of post-translational modifications of proteins, mostly histones, on chromatin structure and accessibility. The other one deals with parental genomic imprinting, a process which allows to express a few selected genes from only one of the parental allele while extinguishing the other.
Download or read book DNA Methylation written by J. Jost and published by Birkhäuser. This book was released on 2013-11-11 with total page 581 pages. Available in PDF, EPUB and Kindle. Book excerpt: The occurrence of 5-methylcytosine in DNA was first described in 1948 by Hotchkiss (see first chapter). Recognition of its possible physiologi cal role in eucaryotes was first suggested in 1964 by Srinivasan and Borek (see first chapter). Since then work in a great many laboratories has established both the ubiquity of 5-methylcytosine and the catholicity of its possible regulatory function. The explosive increase in the number of publications dealing with DNA methylation attests to its importance and makes it impossible to write a comprehensive coverage of the literature within the scope of a general review. Since the publication of the 3 most recent books dealing with the subject (DNA methylation by Razin A. , Cedar H. and Riggs A. D. , 1984 Springer Verlag; Molecular Biology of DNA methylation by Adams R. L. P. and Burdon R. H. , 1985 Springer Verlag; Nucleic Acids Methylation, UCLA Symposium suppl. 128, 1989) considerable progress both in the techniques and results has been made in the field of DNA methylation. Thus we asked several authors to write chapters dealing with aspects of DNA methyla tion in which they are experts. This book should be most useful for students, teachers as well as researchers in the field of differentiation and gene regulation. We are most grateful to all our colleagues who were willing to spend much time and effort on the publication of this book. We also want to express our gratitude to Yan Chim Jost for her help in preparing this book.
Download or read book Epigenome Editing written by Albert Jeltsch and published by Springer Nature. This book was released on with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Stem Cell Epigenetics written by and published by Academic Press. This book was released on 2020-08-07 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Growing evidence suggests that epigenetic mechanisms play a central role in stem cell biology and are vital for determining gene expression during cellular differentiation and governing mammalian development. In Stem Cell Epigenetics, leading international researchers examine how chromatin regulation and bona fide epigenetic mechanisms underlie stem cell renewal and differentiation. Authors also explore how the diversity of cell types, including the extent revealed by single cell omic approaches, is achieved, and how such processes may be reversed or managed via epigenetic reprogramming. Topics discussed include chromatin in pluripotency, stem cells and DNA methylation, histone modifications in stem cells and differentiation, higher-order chromatin conformation in pluripotent cells, stem cells and cancer, epigenetics and disease modeling, brain organoids from pluripotent cells, transcriptional regulation in stem cells and differentiation, non-coding RNAs in pluripotency and early differentiation, and diseases caused by epigenetic alterations in stem cells. Additionally, the book discusses the potential implementation of stem cell epigenetics in drug discovery, regenerative medicine, and disease treatment. Stem Cell Epigenetics will provide researchers and physicians with a state-of-the-art map to orient across the frontiers of this fast-evolving field. Analyzes the role of epigenetics in embryonic stem cell regulation Indicates the epigenetic mechanisms involved in stem cell differentiation and highlights modifications and misregulations that may result in disease pathogenesis Examines the potential applications of stem cell epigenetics in therapeutic disease interventions and regenerative medicine, providing a foundation for researchers and physicians to bring this exciting and fast-evolving field into a clinical setting Features chapter contributions by leading international experts
Download or read book Next Generation Sequencing written by Jerzy Kulski and published by BoD – Books on Demand. This book was released on 2016-01-14 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Next generation sequencing (NGS) has surpassed the traditional Sanger sequencing method to become the main choice for large-scale, genome-wide sequencing studies with ultra-high-throughput production and a huge reduction in costs. The NGS technologies have had enormous impact on the studies of structural and functional genomics in all the life sciences. In this book, Next Generation Sequencing Advances, Applications and Challenges, the sixteen chapters written by experts cover various aspects of NGS including genomics, transcriptomics and methylomics, the sequencing platforms, and the bioinformatics challenges in processing and analysing huge amounts of sequencing data. Following an overview of the evolution of NGS in the brave new world of omics, the book examines the advances and challenges of NGS applications in basic and applied research on microorganisms, agricultural plants and humans. This book is of value to all who are interested in DNA sequencing and bioinformatics across all fields of the life sciences.
Download or read book Cellular Ecophysiology of Microbe written by Tino Krell and published by Springer. This book was released on 2018-03-24 with total page 585 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book assembles concisely written chapters by world-leaders in the field summarizing recent advances in understanding microbial responses to hydrocarbons. Subjects treated include mechanisms of sensing, hydrocarbon tolerance and degradation as well as an overview on hydrophobic modification of biomolecules. Other chapters are dedicated to issues related to the reduced bioavailability of hydrocarbons, which differentiates this class of compounds form many others, but which of central importance to understand the ecophysiological consequences. This book should be standard literature in any laboratory working in this area.
