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Epigenetic Determinants of Cellular Differentiation, Transcriptional Reprogramming, and Human Disease

Author : Khoi Thien Nguyen
Publisher :
Page : 130 pages
File Size : 48,92 MB
Release : 2020
Category :
ISBN :

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Much of the diversity we observe in cellular and organismal phenotypes can be attributed to epigenetic and genetic variation. DNA provides the instructions for life, while epigenetic modifications regulate which parts of the genetic information contained in DNA can be read out in a given cell and how this information is interpreted. In recent years, epigenetic and genetic variation has been profiled on a large scale with sequencing-based assays, generating many datasets to be explored. In this thesis, I present three projects which apply computational techniques to identify and characterize epigenetic mechanisms that may contribute to the regulation of phenotypic variance. First, we mine a dataset charactering the epigenomes of diverse cell types in order to discover signatures of adult stem cell differentiation. We identify a novel marker of the multipotent state, a chromatin state characterized by the histone marks H3K36me3 and H3K9me3, and describe biological processes that may be linked to the loss of this chromatin state in fully differentiated cell types. Next, I present what we learned from profiling the epigenetic state of cells before and after transplantation into Xenopus oocytes, a process that transcriptionally reprograms the cells. This analysis elucidates how the initial epigenetic state of a cell influences the success of cellular reprogramming and identifies transcription factors that help regulate this process. Finally, we integrate studies measuring the effects of genetic variants on disease with studies measuring the effects of genetic variants on transcriptional and epigenetic activity. This identifies specific mechanisms underlying disease processes, and demonstrates that transcriptional and epigenetic mechanisms may independently contribute to disease pathogenesis. Together, these projects demonstrate the biological insights that can be gained from epigenetic profiling, and expand our understanding of the potential effects of epigenetic modifications.

Epigenetic Mechanisms in Cellular Reprogramming

Author : Alexander Meissner
Publisher : Springer
Page : 244 pages
File Size : 12,65 MB
Release : 2014-12-11
Category : Medical
ISBN : 3642319742

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The ability of a single genome to give rise to hundreds of functionally distinct cell type programs is in itself remarkable. Pioneering studies over the past few decades have demonstrated that this plasticity is retained throughout development, a phenomenon of epigenetic programming and reprogramming that remains one of the most fascinating areas of modern biology, with major relevance to human health and disease. This book presents the basic biology involved, including key mechanistic insights into this rapidly growing field.

Human Epigenetics: How Science Works

Author : Carsten Carlberg
Publisher : Springer Nature
Page : 153 pages
File Size : 48,12 MB
Release : 2019-09-24
Category : Medical
ISBN : 3030229076

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The view “It’s all in our genes and we cannot change it” developed in the past 150 years since Gregor Mendel’s experiments with flowering pea plants. However, there is a special form of genetics, referred to as epigenetics, which does not involve any change of our genes but regulates how and when they are used. In the cell nucleus our genes are packed into chromatin, which is a complex of histone proteins and genomic DNA, representing the molecular basis of epigenetics. Our environment and lifestyle decisions influence the epigenetics of our cells and organs, i.e. epigenetics changes dynamically throughout our whole life. Thus, we have the chance to change our epigenetics in a positive as well as negative way and present the onset of diseases, such a type 2 diabetes or cancer. This textbook provides a molecular explanation how our genome is connected with environmental signals. It outlines that epigenetic programming is a learning process that results in epigenetic memory in each of the cells of our body. The central importance of epigenetics during embryogenesis and cellular differentiation as well as in the process of aging and the risk for the development of cancer are discussed. Moreover, the role of the epigenome as a molecular storage of cellular events not only in the brain but also in metabolic organs and in the immune system is described. The book represents an updated but simplified version of our textbook “Human Epigenomics” (ISBN 978-981-10-7614-8). The first five chapters explain the molecular basis of epigenetics, while the following seven chapters provide examples for the impact of epigenetics in human health and disease.

Epigenetics: Development and Disease

Author : Tapas Kumar Kundu
Publisher : Springer Science & Business Media
Page : 698 pages
File Size : 32,17 MB
Release : 2012-11-13
Category : Medical
ISBN : 9400745257

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Epigenetics fine-tunes the life processes dictated by DNA sequences, but also kick-starts pathophysiological processes including diabetes, AIDS and cancer. This volume tracks the latest research on epigenetics, including work on new-generation therapeutics.

Transcriptional and Translational Regulation of Stem Cells

Author : Gary Hime
Publisher : Springer Science & Business Media
Page : 370 pages
File Size : 30,14 MB
Release : 2013-05-22
Category : Medical
ISBN : 9400766211

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This volume describes the latest findings on transcriptional and translational regulation of stem cells. Both transcriptional activators and repressors have been shown to be crucial for the maintenance of the stem cell state. A key element of stem cell maintenance is repression of differentiation factors or developmental genes – achieved transcriptionally, epigenetically by the Polycomb complex, and post-transcriptionally by RNA-binding proteins and microRNAs. This volume takes two approaches to this topic – (1) illustrating the general principles outlined above through a series of different stem cell examples – embryonic, iPS and adult stem cells, and (2) describing several molecular families that have been shown to have roles in regulation of multiple stem cell populations.

Stem Cell Epigenetics

Author :
Publisher : Academic Press
Page : 318 pages
File Size : 22,37 MB
Release : 2020-08-13
Category : Medical
ISBN : 0128140852

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Stem Cell Epigenetics, Volume 16, examines how epigenetics are involved in stem cell differentiation, how a stem cell rapidly transitions into a molecularly distinct cell type, and how this process may be reversed or managed via epigenetic reprogramming. Topics discussed include chromatin in pluripotency, epigenetic regulation of reprogramming, stem cells and DNA methylation, histone modifications in stem cells and differentiation, higher-order chromatin conformation in pluripotent cells, epigenetics and disease modeling, 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 potential implementation of stem cell epigenetics in drug discovery, regenerative medicine, and disease treatment is discussed in detail, helping researchers and physicians bring this exciting and fast evolving field to the clinic. Provides genetic researchers, students and physicians with evidence indicating the epigenetic mechanisms involved in stem cell differentiation Highlights the specific characteristics of the epigenetic modifications and misregulations that may result in disease pathogenesis Examines the potential application of stem cell epigenetics towards developing therapeutic interventions for disease and advancing regenerative medicine Features chapter contributions by leading international experts

Epigenetic Mechanisms of Gene Regulation

Author : Vincenzo E. A. Russo
Publisher :
Page : 716 pages
File Size : 45,57 MB
Release : 1996
Category : Medical
ISBN :

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Many inheritable changes in gene function are not explained by changes in the DNA sequence. Such epigenetic mechanisms are known to influence gene function in most complex organisms and include effects such as transposon function, chromosome imprinting, yeast mating type switching and telomeric silencing. In recent years, epigenetic effects have become a major focus of research activity. This monograph, edited by three well-known biologists from different specialties, is the first to review and synthesize what is known about these effects across all species, particularly from a molecular perspective, and will be of interest to everyone in the fields of molecular biology and genetics.

Epigenetics

Author : Lyle Armstrong
Publisher : Garland Science
Page : 319 pages
File Size : 27,20 MB
Release : 2013-11-20
Category : Science
ISBN : 1317683153

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The concept of epigenetics has been known about since the 1940s, but it is only in the last 10 years that research has shown just how wide ranging its effects are. It is now a very widely-used term, but there is still a lot of confusion surrounding what it actually is and does. Epigenetics is a new textbook that brings together the structure and machinery of epigenetic modification, how epigenetic modification controls cellular functions, and the evidence for the relationship between epigenetics and disease. It is a valuable source of information about all aspects of the subject for undergraduate students, graduate students, and professionals.