Tet Proteins And Dna Demethylation PDF Download
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Author | : Ozren Bogdanovic |
Publisher | : Humana |
Total Pages | : 320 |
Release | : 2021-05-20 |
Genre | : Science |
ISBN | : 9781071612934 |
Download TET Proteins and DNA Demethylation Book in PDF, ePub and Kindle
This volume explores the latest methods used to study various aspects of TET proteins and their biology. Chapters in this book are divided into five parts. Part One describes technologies aimed at detecting and quantifying DNA methylation turnover using massively parallel sequencing, ELISA, and mass spectrometry approaches. Part Two looks at data analyses protocols for distinguishing acting versus passive DNA demethylation and estimation of 5mC and 5hmC levels. Part Three deals with a new topic that takes advantage of modified CRISPR/Cas9 genome editing systems to target DNA demethylation activity to genomic loci of interest. Part Four discusses protocols that detail how to purify TET proteins and unravel their protein interactions, and Part Five looks at the assessment of TET protein function and activity in vivo and in vitro. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, TET Proteins and DNA Demethylation: Methods and Protocols is a valuable resource that aims to help research scientists at all levels working in the fields of DNA demethylation dynamics. Chapters 3, 7 and 17 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Author | : Michael Lübbert |
Publisher | : Springer Science & Business Media |
Total Pages | : 332 |
Release | : 2013-12-12 |
Genre | : Medical |
ISBN | : 3642384048 |
Download Epigenetic Therapy of Cancer Book in PDF, ePub and Kindle
The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.
Author | : Daniela Samaniego Castruita |
Publisher | : |
Total Pages | : 0 |
Release | : 2022 |
Genre | : |
ISBN | : |
Download Role of TET Proteins in B Cells and Treg Cells Book in PDF, ePub and Kindle
DNA demethylation is promoted by TET enzymes, a family of three proteins--TET1, TET2 and TET3--which oxidize methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). TET proteins have been previously associated to cancer. In particular, Tet2 loss of function is strongly associated to haematopoietic malignancies in humans, such as B cell and T cell lymphoma. In this dissertation we explore the role of TET proteins in B and Treg cells. To do this we rely in the use of in vivo and in vitro models. We generated a mouse model with Tet2/3 deletion, CD19 Tet2/3 DKO mice. The TET deficient mice showed an expansion of Germinal Center B cells and developed B cell lymphoma, as early as 6 weeks of age; coupled to this, we observed an increase of G-quaruplexes and R-loops and increase of DNA damage. Mice generated with the adiddtional [additional] deletion of DNMT1, the enzyme responsible to maintain DNA methylation and also a G-quadruplex binding protein, on top of the Tet2/3 deletion, showed an inhibition of Germinal Center B cells and a significant delay on B cell lymphoma. We also explored the role of TET proteins in Treg cells using genomic and epigenomic approaches in in vivo and in vitro models. The Tet2/3 deficient Treg cells showed a loss of Treg-specific molecular features, and an impairement of IL-2/STAT5 signaling pathway. In our in vitro system, we induced Treg (iTreg) cells with TGF[beta] and treated them with Vitamin C, a potent activator of TET proteins and other dioxygenases. Oposite [opposite] to what we observed in vivo, boosting TET activity with Vitamin C enhanced IL-2 responsiveness in iTreg cells by increasing IL2R[alpha] expression and STAT5 activity.
Author | : George Fink |
Publisher | : Academic Press |
Total Pages | : 346 |
Release | : 2020-10-24 |
Genre | : Science |
ISBN | : 0128131578 |
Download Stress: Genetics, Epigenetics and Genomics Book in PDF, ePub and Kindle
This fourth volume in the Handbook of Stress series, Stress: Genetics, Epigenetics and Genomics, deals with the influence that genetics, epigenetics, and genomics have on the effects of and responses to stress. Chapters refer to epigenetic mechanisms that involve DNA methylation, histone modification, and/or noncoding RNA-associated gene activation or silencing. There is also coverage of epigenetic mechanisms in stress-related transgenerational transmission of characteristics, and how these may help explain heritability in some complex human diseases.The Handbook of Stress series, comprised of self-contained volumes that each focus on a specific stress area, covers the significant advances made since the publication of Elsevier’s Encyclopedia of Stress (2000 and 2007). Volume 4 is ideal for graduate students, post-doctoral fellows, faculty and clinicians interested in stress genetics, epigenetics and genomics involved in neuroendocrinology, neuroscience, biomedicine, endocrinology, psychology, psychiatry and the social sciences Articles carefully selected by eminent stress researchers and prepared by contributors representing outstanding scholarship in the field, with each chapter fully vetted for reliable expert knowledge Richly illustrated with explanatory figures and tables Each chapter includes a boxed “Key points call out section Affordably priced, self-contained volume for readers specifically interested in stress genetics and epigenetics, removing the need to purchase the whole Handbook series
Author | : L. Joseph Su |
Publisher | : Springer |
Total Pages | : 327 |
Release | : 2015-05-18 |
Genre | : Medical |
ISBN | : 1447166787 |
Download Environmental Epigenetics Book in PDF, ePub and Kindle
This book examines the toxicological and health implications of environmental epigenetics and provides knowledge through an interdisciplinary approach. Included in this volume are chapters outlining various environmental risk factors such as phthalates and dietary components, life states such as pregnancy and ageing, hormonal and metabolic considerations and specific disease risks such as cancer cardiovascular diseases and other non-communicable diseases. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses.
Author | : Renato Paro |
Publisher | : Springer Nature |
Total Pages | : 215 |
Release | : 2021-03-23 |
Genre | : Science |
ISBN | : 3030686701 |
Download Introduction to Epigenetics Book in PDF, ePub and Kindle
This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Author | : Antonio Lentini |
Publisher | : Linköping University Electronic Press |
Total Pages | : 65 |
Release | : 2019-03-19 |
Genre | : |
ISBN | : 9176851079 |
Download Dynamic regulation of DNA methylation in human T-cell biology Book in PDF, ePub and Kindle
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.
Author | : Trygve O. Tollefsbol |
Publisher | : Springer Science & Business Media |
Total Pages | : 462 |
Release | : 2009-11-11 |
Genre | : Medical |
ISBN | : 1441906398 |
Download Epigenetics of Aging Book in PDF, ePub and Kindle
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.
Author | : Albert Jeltsch |
Publisher | : Springer |
Total Pages | : 537 |
Release | : 2016-11-08 |
Genre | : Science |
ISBN | : 3319436244 |
Download DNA Methyltransferases - Role and Function Book in PDF, ePub and Kindle
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.
Author | : Isaac Fernando López Moyado |
Publisher | : |
Total Pages | : 122 |
Release | : 2019 |
Genre | : |
ISBN | : |
Download Association of TET Loss of Function with Heterochromatin DNA Hypomethylation and Genome Instability Book in PDF, ePub and Kindle
Cancer genomes are characterized by focal increases in DNA methylation, co-occurring with widespread hypomethylation. Here we show that TET loss-of-function results in a similar genomic footprint. Both 5hmC in wildtype genomes, and DNA hypermethylation in TET-deficient genomes, are largely confined to the active euchromatic compartment, consistent with the known functions of TET proteins in DNA demethylation and the known distribution of 5hmC at transcribed genes and active enhancers. In contrast, an unexpected DNA hypomethylation noted in multiple TET-deficient genomes is primarily observed in the heterochromatin compartment. In a mouse model of T cell lymphoma driven by TET deficiency (Tet2/3 DKO T cells), genomic analysis of malignant T cells revealed DNA hypomethylation in the heterochromatic genomic compartment, as well as reactivation of repeat elements and enrichment for single nucleotide alterations, primarily in heterochromatic regions of the genome. Furthermore, like DNMT-deficient cells, expanded Tet2/3 DKO T cells displayed recurrent aneuploidies and increased accumulation of DNA double-strand breaks. Noteworthy, hematopoietic stem/precursor cells (HSPC) doubly deficient for Tet2 and Dnmt3a displayed greater losses of DNA methylation than HSPC singly deficient for Tet2 or Dnmt3a alone, potentially explaining the unexpected synergy between DNMT3A and TET2 mutations in myeloid and lymphoid malignancies. Tet1-deficient cells showed decreased localization of Dnmt3a in the heterochromatin compartment compared to WT cells, pointing to a functional interaction between TET and DNMT proteins and providing a potential explanation for the hypomethylation observed in TET-deficient genomes. Our data suggest that TET loss-of-function may at least partially underlie the characteristic pattern of global hypomethylation coupled to regional hypermethylation observed in diverse cancer genomes, propose that heterochromatin DNA hypomethylation may at least partially explain some of the shared features between TET and DNMT mutants, and highlight the potential contribution of heterochromatin hypomethylation to oncogenesis.