Download or read book Histone Mutations and Cancer written by Dong Fang and published by Springer Nature. This book was released on 2020-11-06 with total page 102 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on histone mutations, especially those mutations closely related to cancer. Genetic mutations and epigenetic alterations contribute to the development of a variety of cancers: recent genetic studies have identified e.g. H3K27M and H3G34R/V mutation in over 75% of DIPG cases, H3.3K36M mutation in more than 90% of chondroblastoma cases, and H3G34W/L mutation in over 90% of giant cell tumors of bone. Given the high incidence and tumorigenesis effects of histone H3 mutations, they are also referred to as oncohistones. This book highlights the advances made in the area over the past 10 years, and offers a state-of-the-art summary of epigenetic alternation, gene expression, protein structure, drug discovery, immunotherapy, and mouse modeling of histone H3 mutations in various tumors. Chiefly intended to provide researchers and graduate students with an overall picture of these mutations, it will also be of interest to researchers in basic oncology, clinical oncology, and epigenetics, as well as academics and clinical oncology practitioners.
Download or read book The Histone Code and Beyond written by Shelley L. Berger and published by Springer Science & Business Media. This book was released on 2007-01-19 with total page 223 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.
Download or read book Introduction to Epigenetics written by Renato Paro and published by Springer Nature. This book was released on 2021-03-23 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book DNA and Histone Methylation as Cancer Targets written by Atsushi Kaneda and published by Springer. This book was released on 2017-09-04 with total page 624 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will focus on DNA and histone methylation in epigenetics and describe how it is involved in the molecular mechanisms responsible for the development of cancer. Chapters will summarize the current knowledge of the molecular basis of DNA and histone methylation and explain how it is involved in cancer, describe the features of DNA and histone methylation associated with particular types of cancer, diagnostic/therapeutic applications, and future directions of DNA and histone methylation as cancer targets.
Download or read book Characterizing the Transcriptional Impact of Histone H3 Mutations on Cell Identity in Cancer and Development written by Nisha Kabir and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Histone proteins have vital roles in the regulation of gene expression during development, where dysregulation of this processes results in diseases such as cancer and neurological disorders. Pediatric high-grade glioma (pHGG) is a highly aggressive cancer with a two-year survival rate of less than 30%. With the advent of whole genome sequencing, recurrent somatic mutations in histone H3 proteins and common co-occurring partner mutations have been identified to drive a subset of cancer. Histone H3 lysine 27 to methionine (H3K27M) cause a subset of pHGGs occurring in the brain midline in younger children, while mutations in glycine 34 to arginine or valine (G34R/V) cause another subset of pHGGs occurring in the cerebral cortex of adolescents and young adults. Histone H3 mutants also drive cancer outside of the brain, where mutations in glycine 34 to tryptophan (G34W) cause over 90% of giant cell tumors of bone (GCTB) in adults. The restricted pattern of histone mutations with anatomical location and age of incidence in brain tumors gave rise to the hypothesis that histone mutations only occurring in a specific developmental window and cellular context give rise to cancer. While the cellular context is known for these tumors, how the mutations subsequently impact cell identity along differentiation are not well characterized. In this thesis, I study the transcriptomic effect of H3 and partner mutations on cellular identity using in silico integrative analysis of genome-wide transcriptomic data from model systems and normal references of the developing brain at single-cell resolution. I will use a variety computational methods to map genome-wide transcriptomic data to normal references to infer changes to cell identity in disease states. First, I study the role of partner mutations in a kinase, ACVR1, in the context of mutant H3 K27M. Gene expression profiling shows that mutations in ACVR1 impact cellular identity in distinct ways depending on the histone context. Second, I study the effect of H3.3 K27M mutations using cell lines subjected to differentiation experiments and orthotopic xenograft models using an isogenic system. In vivo K27M-KO experiments show a difference in cell state towards oligodendrocyte and astrocyte lineages, while in vitro K27M-KO experiments show upregulation of extracellular matrix and cellular adhesion gene programs. Third, I study the transcriptomic effects of germline heterozygous H3.3 G34R/V/W mutations in murine models. Germline G34 mutants have surprising tissue specificity; G34R mutants cause progressive neuronal loss coupled to increased immune infiltration in the brain, while G34W mutants cause an unhealthy obesity phenotype with decreased expression of PPARG, a master regulator of adipocyte differentiation. Together, this work provides insight into changes in cell identity and neurological abnormalities induced by H3 mutations at the level of transcription. This represents an important step in characterizing the cellular contexts of these disease states for the development of therapeutics"--
Download or read book The Histone Code and Beyond written by Shelley L. Berger and published by Springer. This book was released on 2009-09-02 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.
Download or read book Histone Modifications in Therapy written by Pedro Castelo-Branco and published by Academic Press. This book was released on 2020-08-21 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Histone Modifications in Therapy provides an in-depth analysis of the role of histone mechanisms in major diseases and the promise of targeting histone modifications for disease prevention and treatment. Here, researchers, clinicians and students will discover a thorough, evidence-based discussion of the biology of histones, the diseases engaged by aberrant histone modifications, and pathways with therapeutic potential. Expert chapter addresses the role of histone modifications across a variety of disorders, including cancer, neuropsychiatric, neurodegenerative, cardiac, metabolic, infectious, bacterial, autoimmune and inflammatory disorders, among others. In relation to these disease types, histone modifications are discussed, both as mechanisms of prevention and possible treatment. A concluding chapter brings together future perspectives for targeting histone modifications in therapy and next steps in research. Examines the use of histone modifications in disease prevention and therapy Explores the role of histone modifications in cancer, neuropsychiatric, neurodegenerative, cardiac, metabolic, infectious, bacterial, and inflammatory disease, among others Features chapters from a broad range of international authors and disease specialists
Download or read book Epigenetics and Cancer Part A written by and published by Academic Press. This book was released on 2010-11-22 with total page 411 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genes interact with the environment, experience, and biology of the brain to shape an animal’s behavior. This latest volume in Advances in Genetics, organized according to the most widely used model organisms, describes the latest genetic discoveries in relation to neural circuit development and activity. Explores the latest topics in neural circuits and behavior research in zebrafish, drosophila, C.elegans, and mouse models Includes methods for testing with ethical, legal, and social implications Critically analyzes future prospects
Download or read book Cancer Epigenetics written by Trygve Tollefsbol and published by CRC Press. This book was released on 2008-09-19 with total page 472 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the past few decades, it has become increasingly apparent that heredity is not the sole determining factor in disease development, such as cancer. This landmark work covers a wide array of aspects in the relatively new area of epigenetics, ranging from its role in the basic mechanisms of tumorigenesis, to the newest epigenetic drugs being de
Download or read book A Study of Histone H2B Mutations in Cancer written by 劉嘉賢 and published by . This book was released on 2020 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Clinical Epigenetics written by Luke B. Hesson and published by Springer Nature. This book was released on 2019-08-31 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: In genetic pathology, epigenetic testing is rare and under utilised. In this book, we introduce epigenetics to a non-expert scientific audience and describe current and future clinical utility of epigenetic testing. By focussing on epigenetics in human disease this book will guide professionals (scientists and clinicians) to understand how epigenetics is relevant in a clinical context, and to implement epigenetic testing in diagnostic laboratories. The book begins with a historical perspective of genetics and epigenetics and describes the work of pioneers who have helped shape these fields. The various mechanisms by which epigenetics can regulate the function of the genome is described. These include DNA methylation, histone modifications, histone variants, nucleosome positioning, cis-regulatory elements, non-coding RNAs and the three-dimensional organisation of chromatin in the nucleus. These are discussed in the context of embryological development, cancer and imprinting disorders, and include examples of epigenetic changes that can be used in diagnosis, prediction of therapeutic response, prognostication or disease monitoring. Finally, for those wishing to implement epigenetic testing in a diagnostic setting, the book includes a case study that illustrates the clinical utility of epigenetic testing.
Download or read book Functional Characterization of Histone H3 3 glycine 34 Mutations in Development and Cancer written by Sima Khazaei and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Recurrent mutations impacting the glycine 34 codon of H3F3A encoding noncanonical H3 variant H3.3 arise in specific cancers: G34R and rarely G34V mainly occur in high grade gliomas (HGGs) of the cerebral cortex, while G34W characterize 90% of a specific bone cancer, giant cell tumor of the bone (GCTB). There is limited information on H3.3G34-mutant's oncogenic mechanisms. Using an innovative initial mosaic step approach, we generated direct knock-in (DKI) mice carrying heterozygous germline H3.3 (H3f3a) G34R, V or W mutations. Our data in two different mouse genetic backgrounds consistently show drastically distinct phenotypes between G34R and W mutant mice, while H3.3G34V mice show a similar but milder phenotype to that observed in H3.3G34R DKI mice and no phenotype is observed in mice carrying a deletion of one H3f3a allele. Indeed, severe neurological issues are observed in G34R mutant mice and to a lesser degree in G34V, while minor neurological insults are observed in G34W mice, which in contrast have bladder and uretero-genital issues. All G34 mutant mice exhibit an obesity phenotype, which is most severe in G34W mice. This is consistent with patient data where G34R/V mutations in H3F3A seem exclusive to HGG of the brain while H3.3G34W are specific to mesenchymal tumors namely GCTB. GCTB are characterized by a neoplastic H3.3G34W-mutant stromal population and a bone-resorptive giant osteoclast population. The mechanism by which the H3.3G34W mutation alters the epigenome to give rise to GCTB remains unknown. Here, we generated isogenic cell lines from patient derived GCTB stromal cultures and defined the epigenetic and transcriptomic changes mediated by H3.3G34W. G34W induced H3.3K36me3 loss and H3.3K27me3 gain on mutant H3.3 histones. We show that H3.3G34W promotes H3K27me3 redistribution from intergenic to genic regions. This epigenetic dysregulation and associated transcriptional changes are linked to cell identity, with upregulation of extracellular matrix organization genes and downregulation of contractile actomyosin pathways in H3.3G34W cells. Single-cell transcriptomics of GCTB tumors reveals that G34W stromal cells resemble osteoblast progenitors with distinct populations comprising a neoplastic trajectory from an SPP1+IBSP+ osteoblast-like population towards an ACTA2+ contractile population. Correction of the H3.3G34W mutation by CRISPR-Cas9 in GCTB stromal cells results in increased progression to myogenic differentiation along this trajectory in vitro. We further show that ACTA2+ contractile H3.3G34W stromal cells secrete ligands promoting extracellular matrix remodeling, likely facilitating association and recruitment of osteoclasts. Importantly, orthotopic tibial injection of H3.3G34W, but not isogenic CRISPR-edited stromal cells, resulted in aggressive osteolytic tumors with recruitment of murine multinucleated osteoclasts, indicating a persistent requirement for H3.3G34W mutation in GCTB tumorigenesis"--
Download or read book Epigenetic Mechanisms of Gene Regulation written by Vincenzo E. A. Russo and published by . This book was released on 1996 with total page 716 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Chromatin and Genomic Instability in Cancer written by and published by Academic Press. This book was released on 2021-09-08 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromatin and DNA Repair in Cancer, Volume 364 in the International Review of Cell and Molecular Biology series reviews and details current advances in cell and molecular biology. Chapters in this new release cover Genomic Instability and metabolism in cancer, Histones variants and Histones modifications in cancer and Aging, DNA Double-stranded breaks Repair in Cancer, Reactive oxygen species and DNA damage response in cancer, Transcription-Associated DNA Breaks and Cancer: A Matter of DNA Topology, Mechanisms of Base Excision Repair: Its Significance to Human Health, and more. The IRCMB series has a worldwide readership, maintaining a high standard by publishing invited articles on important and timely topics that are authored by prominent cell and molecular biologists. The articles published in IRCMB have a high impact and an average cited half-life of 9 years. This great resource ranks high amongst scientific journals dealing with cell biology. Publishes only invited review articles on selected topics Authored by established and active cell and molecular biologists, drawn from international sources Offers a wide range of perspectives on specific subjects
Download or read book Systems Analysis of Chromatin Related Protein Complexes in Cancer written by Andrew Emili and published by Springer Science & Business Media. This book was released on 2013-08-13 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic modifications underlie all aspects of human physiology, including stem cell renewal, formation of cell types and tissues. They also underlie environmental impacts on human health, including aging and diseases like cancer. Consequently, cracking the epigenetic "code" is considered a key challenge in biomedical research. Chromatin structure and function are modified by protein complexes, causing genes to be turned “on” or “off” and controlling other aspects of DNA function. Yet while there has been explosive growth in the epigenetics field, human chromatin-modifying machines have only recently started to be characterized. To meet this challenge, our book explores complementary experimental tracks, pursued by expert international research groups, aimed at the physical and functional characterization of the diverse repertoire of chromatin protein machines - namely, the "readers, writers and erasers" of epigenomic marks. These studies include the identification of RNA molecules and drugs that interact selectively with components of the chromatin machinery. What makes this book distinctive is its emphasis on the systematic exploration of chromatin protein complexes in the context of human development and disease networks.
Download or read book Epigenetic Regulation of Cancer in Response to Chemotherapy written by and published by Elsevier. This book was released on 2023-03-27 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Regulation of Cancer in Response to Chemotherapy, Volume 158 of the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting chapters on timely topics, including Epigenetically Programmed Resistance to Chemotherapy and Promotion of Immune Evasion in Cancer, A Role for the Epigenome in Cancer Cell Drug Tolerance, Histone Methylation and X Chromosomal Genes in Metastasis of Breast Cancer, Targeting Epigenetic Regulation Using Small Molecule Inhibitors, Histone Deacetylase Inhibitors as Sanguine Epigenetic Therapeutics against Pugnacious Lung Cancer, From ecology to oncology: To understand cancer stem cell dormancy, ask a Brine shrimp (Artemia), and more. Additional chapters cover Predictive Models of Chemoresistance Generated by Crunching the Public Drug Screen, Epigenomic and Genomic Profiling Datasets via Regression-, Machine Learning, and Knowledge-Based Methods, Probing on the Mechanisms of lncRNAs on Cancer Drug Resistance, Drug Tolerant Persister Cells in Cancer: Current Knowledge and Therapeutic Perspectives, and much more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Cancer Research series Includes the latest information on the Epigenetic Regulation of Cancer in Response to Chemotherapy
Download or read book Elucidating the Epigenetic and Transcriptional Impact of Mutant H3 in Cancer written by Nicolas De Jay and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Pediatric high-grade glioma (pHGG) is an incurable disease with less than 10% overall survival at 5 years. The deadliest subset is prevalent in the youngest patients, mostly restricted to the midline, and carries lysine 27 to methionine mutations in histone H3 (H3K27M). Outside of the brain, H3 mutant cancers show similarly restricted patterns of incidence: glycine 34 to tryptophan mutations (H3G34W) occur in the majority (92%) of giant cell tumors of the bone (GCTB) but not elsewhere. In the normal setting, histone H3 plays a conserved role in epigenetic patterning during development via major antagonistic repressive (H3K27me3 and H3K9me3) and active (H3K27ac, H3K36me2 and H3K36me3) chromatin marks. Mutations disrupting these marks appear to be tumor- promoting only in the right cell type, at the right time, on the right residue of H3. The incomplete understanding of the context-dependent effects of mutant H3 has been a major obstacle to the development of effective therapies for these devastating diseases.In this thesis, I present a study of the epigenetic and transcriptional impact of mutant H3 in cancer using integrative multi-omic approaches and model systems that provide appropriate cellular conditions for oncogenic transformation by mutant H3. First, I describe a preclinical mouse model that highlights cellular conditions amenable to transformation by H3K27M. The model faithfully recapitulates gene expression and deposition patterns of the repressive H3K27me3 in human pHGG. Second, I show how isogenic cellular models allow us to decouple the impact of the cell of origin from that of the mutation on the activating H3K27ac mark and its transcriptional consequences in the search for actionable targets. H3K27M induces a baseline derepression of repetitive elements in pHGG that can be exacerbated using epigenetic therapies and that may therefore carry therapeutic potential. Third, I define the molecular impact of the poorly understood H3G34W mutant in GCTB and show its association with a global chromatin remodeling of major antagonistic marks that may promote a change in cell identity. This thesis provides valuable insights into transcriptomic and epigenetic anomalies caused by H3 mutants H3K27M and H3G34W on pHGG and GCTB. They represent an important first step towards unravelling the pathophysiology of cancers driven by mutant H3 and highlighting therapeutic opportunities against these diseases"--
