Download or read book Ubiquitin proteasome System Regulation of the Chromatin Remodeling and Modification Factors in Orchestrating Gene Expression written by Priyanka Barman and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene expression is central to normal cellular functions and health. Thus, misregulation/alteration of gene expression is associated with cellular pathologies and diseases. In eukaryotes, protein coding gene expression starts in the nucleus at the level of transcription that generates mRNA, which undergoes co-transcriptional processing such as 5'-end capping, 3'-end poly-adenylation, splicing of introns, and subsequent packaging for export through nuclear pores to the cytoplasm for translation to protein. Thus, transcription is an important step of eukaryotic gene expression, which is initiated by the activator protein bound at the specific upstream activating sequence of the gene. Activator targets co-activator that facilitates the assembly of general transcription factors (GTFs) and RNA polymerase II to form the pre-initiation complex (PIC) at the promoter for transcription initiation. Thus, co-activators are important regulators of gene activation. One such co-activator is SAGA (Spt-Ada-Gcn5-Acetyltransferase), a large complex consisting of 20 different proteins. SAGA has multiple structural and functional modules such as TAF (TBP-associated factor), SPT (Suppressor of Ty), HAT (Histone acetyltransferase) and DUB (De-ubiquitinase). During transcription initiation or gene activation, SAGA contacts with activator via its Tra1 subunit, and recruits TBP (TATA-box binding protein) to the promoter via its Spt3 and Spt8 subunits. Subsequently, TBP nucleates the PIC formation to initiate transcription. The PIC formation or transcription requires free DNA template. However, eukaryotic genome is highly packed in the form of chromatin that is an array of nucleosomes, each of which consists of two histone H2A-H2B dimers and one histone H3-H4 tetramer forming an octamer wrapped by about 146 bp (base pair) DNA double helix. Such chromatin/nucleosomal structure of eukaryotic genome occludes the transcription factors to bind the cognate DNA sequence. Therefore, PIC formation and transcription initiation are controlled by chromatin and the factors regulating chromatin. Importantly, in addition to stimulating the PIC formation, the co-activator SAGA regulates chromatin (and hence PIC formation and transcription) via its two distinct enzymatic activities catalyzing histone H3 acetylation and histone H2B de-ubiquitylation. These two enzymatic activities of SAGA are associated with gene expression and cellular functions, alteration of which is associated with cancer and other diseases. The enzymatic activity of the DUB module (that contains Ubp8, Sgf11, Sgf73/ataxin-7 and Sus1) of SAGA is controlled by its Sgf73/ataxin-7 subunit that connects the DUB module with the rest of SAGA, and hence maintains SAGA's overall structural integrity and DUB activity. Consistently, the loss of Sgf73/ataxin-7 impairs SAGA's overall structural integrity, PIC formation and transcription. Thus, functional alteration/misregulation of Sgf73/ataxin-7 is likely to develop cellular pathologies. Indeed, alteration of Sgf73/ataxin-7 abundance or its malfunction/mutation is associated with various diseases such as cancer, early childhood blindness, neurodegenerative disorders, attention-deficit/hyperactivity disorder and ocular coloboma. Therefore, it is important to know the factors/mechanisms that change the cellular level of Sgf73/ataxin-7 towards understanding the disease pathogenesis and therapeutic interventions. However, the regulation of Sgf73/ataxin-7 is poorly understood. In view of this, we have carried out experiments to understand the regulation of Sgf73/ataxin-7 in yeast and human cells. Our results in yeast reveal that Sgf73/ataxin-7 undergoes ubiquitylation and 26S proteasomal degradation, thus unveiling a novel ubiquitin-proteasome system (UPS) regulation of Sgf73/ataxin-7. Alteration of such regulation changes cellular Sgf73/ataxin-7 abundance that affects the PIC formation and transcription. Thus, UPS fine-tunes Sgf73/ataxin-7 in orchestrating the PIC formation and transcription. Therefore, our results reveal a novel UPS regulation of Sgf73/ataxin-7 with physiological relevance in gene expression in yeast. Likewise, we find in human cells that ataxin-7 undergoes ubiquitylation and proteasomal degradation. Alteration of such regulation changes ataxin-7's abundance that is associated with transcription aberration and cellular pathologies, thus implicating altered UPS regulation of ataxin-7 in diseases. Therefore, our results unveil a novel UPS regulation of Sgf73/ataxin-7 in yeast and human cells for normal cellular health, and implicate the alteration of such regulation in diseases. Further, increased or decreased level of Sgf73 impairs the assembly of DUB with the rest of SAGA, thus altering histone H2B ubiquitylation that is associated with transcription elongation. Histone H2B ubiquitylation regulates transcription elongation in collaboration with an evolutionarily conserved chromatin remodeling factor, FACT (Facilitates chromatin transcription), via direct interaction. FACT is a heterodimer of Spt16 and Pob3 in yeast or SSRP1 in humans. Spt16 contains four conserved domains. One such domain is CTD (C-terminal domain) that is negatively charged and intrinsically disordered, and binds to histone H2A-H2B dimer, thus impairing histone-DNA interaction and hence chromatin assembly/disassembly. However, there has not been any study so far to analyze the role of this intrinsically disordered region (IDR) of Spt16 in regulation of chromatin dynamics and transcription in living cells. To address this, we have depleted the CTD/IDR of Spt16, and then analyzed chromatin assembly, disassembly and transcription. Intriguingly, our results reveal that the IDR of Spt16 facilitates chromatin disassembly at the promoter as well as PIC formation and transcription, even though this domain is not required for cellular viability. Thus, our results demonstrate the roles of an IDR of Spt16 in regulating chromatin and transcription, hence advancing our understanding of the FACT regulation of chromatin and gene expression. While FACT is known to regulate transcription and chromatin, it is intriguingly found to be upregulated in cancers, especially aggressive and poorly differentiated tumors. However, how FACT is upregulated in aggressive tumor cells remained unknown until our recent studies that demonstrated ubiquitylation and proteasomal degradation of the Spt16 subunit of FACT in yeast, mouse and human cells in controlling transcription of the genes including the ones associated with cancer. In yeast, Spt16 is ubiquitylated by San1 (an E3 ubiquitin ligase that is involved in nuclear protein quality control) and degraded by the 26S proteasome. However, the role of San1 in genome-wide transcription remained unknown until our recent studies. Such knowledge would provide novel function of a nuclear quality control protein in global gene expression. To address this, we analyzed the role of San1 in the PIC formation and RNA polymerase II elongation genome-wide. Intriguingly, our results demonstrate distinct roles of San1 in regulation of the PIC formation and elongating RNA polymerase II (and hence transcription) genome-wide, thus revealing novel gene regulation by a nuclear protein quality control factor, San1. To determine the role of San1 in regulating transcription via FACT, we carried out a set of experiments including TAP-MS (Tandem affinity purification - mass spectrometry). Our analysis revealed that FACT interacts with a large number of proteins involved in regulation of chromatin, transcription, DNA repair and replication, and several of these interactions are altered in the absence of San1. The factors with altered interactions in the absence of San1 include transcription and chromatin regulatory factors. Thus, our results provide insights as to how San1 regulates transcription via regulation of FACT and its interaction with other proteins, hence advancing our understanding of FACT's interactions, functions and regulation. Collectively, our results reveal novel regulations of the key chromatin and transcription regulatory factors, SAGA and FACT, in controlling gene expression with mechanistic insights and implications in understanding disease pathogenesis (with impact on future targeted therapeutic development).

Download or read book The Ubiquitin Proteasome System written by Thibault Mayor and published by Humana. This book was released on 2019-10-06 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: “This volume explores numerous techniques used to study the ubiquitin proteasome system. The chapters in this book are organized into five parts and cover topics such as determining the mechanisms of action for E2s, E3s, and DUB enzymes; the latest advances to study the formation of poly-ubiquitin chains as well as their linkage types; the binding partners of proteins in the UPS; methods for structure determination by x-ray crystallography, cryo electron microscopy and SAXS; screening assays to select for degrons or modulators of E3s and DUBs; proteomics approaches in the ubiquitin field and methods to study 26S proteasome function. 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. Thorough and authoritative, The Ubiquitin Proteasome System: Methods and Protocols is a valuable resource for both experienced and novice scientists who are interested in expanding their knowledge in this field.

Download or read book DNA Damage Recognition written by Wolfram Siede and published by CRC Press. This book was released on 2005-09-19 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stands as the most comprehensive guide to the subject-covering every essential topic related to DNA damage identification and repair. Covering a wide array of topics from bacteria to human cells, this book summarizes recent developments in DNA damage repair and recognition while providing timely reviews on the molecular mechanisms employe

Download or read book Chemical Epigenetics written by Antonello Mai and published by Springer Nature. This book was released on 2020-03-31 with total page 569 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an authoritative review of the most significant findings about all the epigenetic targets (writers, readers, and erasers) and their implication in physiology and pathology. The book also covers the design, synthesis and biological validation of epigenetic chemical modulators, which can be useful as novel chemotherapeutic agents. Particular attention is given to the chemical mechanisms of action of these molecules and to the drug discovery prose which allows their identification. This book will appeal to students who want to know the extensive progresses made by epigenetics (targets and modulators) in the last years from the beginning, and to specialized scientists who need an instrument to quickly search and check historical and/or updated notices about epigenetics.

Download or read book Exercise for Cardiovascular Disease Prevention and Treatment written by Junjie Xiao and published by Springer. This book was released on 2017-11-02 with total page 382 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book provides an intensive overview on exercise for cardiovascular disease prevention and treatment, from basic research to clinical practice. The volume firstly summarizes the acute and chronic response to exercise. Secondly, evidence for exercise as medicine for the heart based on clinical studies and basic research is summarized. Thirdly, molecular mechanisms mediating the beneficial effects of exercise including IGF-1-PI3K-AKT signalling, NO signalling, C/EBPB-Cited4 signalling, Non-coding RNAs, epigenetic regulators, mitochondria adaption and exosomes are presented. Finally, exercise dosing, prescription and future prospects are provided. This book will provide valuable reference for researchers in cell biology, physiology, as well as physician, physical therapist in cardiology, sport medicine, etc.

Download or read book Fundamentals of Chromatin written by Jerry L. Workman and published by Springer Science & Business Media. This book was released on 2013-12-04 with total page 594 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​​​​​​​​​​​​​While there has been an increasing number of books on various aspects of epigenetics, there has been a gap over the years in books that provide a comprehensive understanding of the fundamentals of chromatin. ​Chromatin is the combination of DNA and proteins that make up the genetic material of chromosomes. Its primary function is to package DNA to fit into the cell, to strengthen the DNA to prevent damage, to allow mitosis and meiosis, and to control the expression of genes and DNA replication. The audience for this book is mainly newly established scientists ​and graduate students. Rather than going into the more specific areas of recent research on chromatin the chapters in this book give a strong, updated groundwork about the topic. Some the fundamentals that this book will cover include the structure of chromatin and biochemistry and the enzyme complexes that manage it.

Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Download or read book Enzymes of Epigenetics Part B written by and published by Elsevier. This book was released on 2016-07-14 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Enzymes of Epigenetics: Part B, one of two new volumes in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods that are employed in the study of epigenetic regulation, including structural, biochemical, molecular, biological, cellular, computational, and systems approaches. Topics include chromatin structure and histones, posttranslational histone modification enzymes and complexes, histone modification binders, DNA modifications and nucleic acid regulators, epigenetic technologies, and small molecule epigenetic regulators and biological connections. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Contains two new volumes that cover research methods in enzymes of epigenetics - Covers such topics as chromatin structure and histones, posttranslational histone modification enzymes and complexes, histone modification binders, DNA modifications and nucleic acid regulators, epigenetic technologies and small molecule epigenetic regulators, and biological connections

Download or read book Index Medicus written by and published by . This book was released on 2001 with total page 1628 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

Download or read book Neuropsychiatric Disorders and Epigenetics written by Jacob Peedicayil and published by Elsevier. This book was released on 2023-09-29 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuropsychiatric Disorders and Epigenetics, Second Edition is a comprehensive reference on the epigenetic basis of common neuropsychiatric disorders. The volume is organized into chapters covering individual neuropsychiatric disorders, from addiction to anxiety and autism spectrum disorders, and is contributed by leading experts in their respective fields. The epigenetic aspects of each disorder are discussed, in the context of the full range of associated epigenetic mechanisms, including DNA modification, histone post-translational modification, chromatin organization, and non-coding RNA. A particular emphasis is placed on potential epigenetic interventions, when the effects of environmental stimuli on epigenetic states is particularly relevant to disease.This new edition has been fully updated to reflect recent research advances enabled by genomic technologies, as well as therapeutic interventions for previously unmanageable disorders. Several new chapters have been added on disorders or approaches not considered in the earlier edition, including epigenetics and anxiety disorders, epigenetics and neuroimaging in neuropsychiatric disorders, genome-wide approaches to epigenetic research, and the epigenetics of spinal muscular atrophy. By helping to define epigenetics as a key player in neuropsychiatric disorders, this volume empowers new research, clinical translation, and pharmacological advances, and highlights promising directions for ongoing investigation. - Analyzes the effects of environmental stimuli on epigenetic states that correlate with neuropsychiatric disease induction - Reviews the epigenetic basis for common neuropsychiatric disorders, thereby guiding translational therapies for clinicians and mechanistic studies for scientists - Features extensive use of diagrams, illustrations, tables, and graphical abstracts for each section to reinforce understanding - - Includes chapter contributions from leading global experts

Download or read book Hi C Data Analysis written by Silvio Bicciato and published by Humana. This book was released on 2022-09-04 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume details a comprehensive set of methods and tools for Hi-C data processing, analysis, and interpretation. Chapters cover applications of Hi-C to address a variety of biological problems, with a specific focus on state-of-the-art computational procedures adopted for the data analysis. 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. Authoritative and cutting-edge, Hi-C Data Analysis: Methods and Protocols aims to help computational and molecular biologists working in the field of chromatin 3D architecture and transcription regulation.

Download or read book Principles of Nutrigenetics and Nutrigenomics written by Raffaele De Caterina and published by Academic Press. This book was released on 2019-09-22 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Nutrigenetics and Nutrigenomics: Fundamentals for Individualized Nutrition is the most comprehensive foundational text on the complex topics of nutrigenetics and nutrigenomics. Edited by three leaders in the field with contributions from the most well-cited researchers conducting groundbreaking research in the field, the book covers how the genetic makeup influences the response to foods and nutrients and how nutrients affect gene expression. Principles of Nutrigenetics and Nutrigenomics: Fundamentals for Individualized Nutrition is broken into four parts providing a valuable overview of genetics, nutrigenetics, and nutrigenomics, and a conclusion that helps to translate research into practice. With an overview of the background, evidence, challenges, and opportunities in the field, readers will come away with a strong understanding of how this new science is the frontier of medical nutrition. Principles of Nutrigenetics and Nutrigenomics: Fundamentals for Individualized Nutrition is a valuable reference for students and researchers studying nutrition, genetics, medicine, and related fields. - Uniquely foundational, comprehensive, and systematic approach with full evidence-based coverage of established and emerging topics in nutrigenetics and nutrigenomics - Includes a valuable guide to ethics for genetic testing for nutritional advice - Chapters include definitions, methods, summaries, figures, and tables to help students, researchers, and faculty grasp key concepts - Companion website includes slide decks, images, questions, and other teaching and learning aids designed to facilitate communication and comprehension of the content presented in the book

Download or read book Ubiquitin and the Biology of the Cell written by Jan-Michael Peters and published by Springer Science & Business Media. This book was released on 1998-05-31 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: The last several years have been a landmark period in the ubiquitin field. The breadth of ubiquitin's roles in cell biology was first sketched, and the importance of ubiquitin-dependent proteolysis as a regulatory mechanism gained general acceptance. The many strands of work that led to this new perception are re counted in this book. A consequence of this progress is that the field has grown dramatically since the first book on ubiquitin was published almost a decade ago [M. Rechsteiner (ed. ), Ubiquitin, Plenum Press, 1988]. In this span, students of the cell cycle, transcription, signal transduction, protein sorting, neuropathology, cancer, virology, and immunology have attempted to chart the role of ubi quit in in their particular experimental systems, and this integration of the field into cell biology as a whole continues at a remarkable pace. We hope that for active researchers in the field as well as for newcomers and those on the fence, this book will prove helpful for its breadth, historical perspective, and practical tips. Structural data are now available on many of the components of the ubiquitin pathway. The structures have provided basic insights into the unusual biochemical mechanisms of ubiquitination and proteasome-mediated proteolysis. Because high-speed computer graphics can convey structures more effectively than print media, we have supplemented the figures of the book with a Worldwide Web site that can display the structures in a flexible, viewer-controlled format.

Download or read book Recurrent Pregnancy Loss written by Asher Bashiri and published by Springer. This book was released on 2016-01-13 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing the latest evidence-based information on etiology, evaluation and treatment, this unique text provides an in-depth, comprehensive discussion of the epidemiology, genetic and endocrinologic factors and medical and surgical management of recurrent pregnancy loss (RPL). Taking a multidisciplinary approach including psychological treatment and patient perspectives, all aspects of current RPL prevention and treatment are elucidated. Detailed chapters provide real-world illustrative material and cover the set-up and management of RPL clinics and databases, containing practical tips. Recurrent Pregnancy Loss will be an excellent resource for OB-GYN specialists, general and reproductive endocrinologists, radiologists, hematologists, psychiatrists, psychologists, and any other investigators or clinicians treating patients confronted with this emotionally and physically trying condition.

Download or read book Epigenetics in Human Disease written by Trygve Tollefsbol and published by Academic Press. This book was released on 2012-07-26 with total page 617 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics is one of the fastest growing fields of sciences, illuminating studies of human diseases by looking beyond genetic make-up and acknowledging that outside factors play a role in gene expression. The goal of this volume is to highlight those diseases or conditions for which we have advanced knowledge of epigenetic factors such as cancer, autoimmune disorders and aging as well as those that are yielding exciting breakthroughs in epigenetics such as diabetes, neurobiological disorders and cardiovascular disease. Where applicable, attempts are made to not only detail the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, but also novel epigenetic approaches to the treatment of these diseases. Chapters are also presented on human imprinting disorders, respiratory diseases, infectious diseases and gynecological and reproductive diseases. Since epigenetics plays a major role in the aging process, advances in the epigenetics of aging are highly relevant to many age-related human diseases. Therefore, this volume closes with chapters on aging epigenetics and breakthroughs that have been made to delay the aging process through epigenetic approaches. With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike. Comprehensive coverage of fundamental and emergent science and clinical usage Side-by-side coverage of the basis of epigenetic diseases and their treatments Evaluation of recent epigenetic clinical breakthroughs

Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

Download or read book Brassinosteroids Plant Growth and Development written by Shamsul Hayat and published by Springer. This book was released on 2019-04-02 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: The entire range of the developmental process in plants is regulated by a shift in the hormonal concentration, tissue sensitivity and their interaction with the factors operating around the plants. Phytohormones play a crucial role in regulating the direction of plant in a coordinated fashion in association with metabolism that provides energy and the building blocks to generate the form that we recognize as a plant. Out of the recognized hormones, attention has largely been focused on Auxins, Gibberellins, Cytokinins, Abscisic acid, Ethylene and more recently on Brassinosteroids. In this book we are providing the information about a brassinosteroids that again confirm its status as phytohormones because it has significant impact on various aspects of the plant life and its ubiquitous distribution throughout the plant kingdom. Brassinosteroids are generating a significant impact on plant growth and development, photosynthesis, transpiration, ion uptake and transport, induces specific changes in leaf anatomy and chloroplast structure. This book is not an encyclopedia of reviews but includes a selected collection of newly written, integrated, illustrated reviews describing our knowledge of brassinosteroids. The aim of this book is to tell all about brassinosteroids, by the present time. The various chapters incorporate both theoretical and practical aspects and may serve as baseline information for future researches through which significant development is possible. It is intended that this book will be useful to the students, teachers and researchers, both in universities and research institutes, especially in relation to biological and agricultural sciences.