Download or read book Characterization of Chromatin Dynamics During DNA Repair and Transcriptional Regulation written by Beth Ann Tamburini and published by . This book was released on 2006 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Role of Chromatin and Transcriptional Regulation in the DNA Damage Response written by Neeraja Vegesna and published by . This book was released on 2021 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA is the repository of genetic information and thus, it is important to maintain its integrity over time and generations. However, DNA can be damaged by a multitude of endogenous and exogenous damaging agents leading to genome instability. In order to maintain genomic integrity and organismal fitness, organisms have evolved highly conserved mechanisms--collectively termed the DNA damage response (DDR)--that coordinate key biological processes needed to repair damaged DNA, including cell cycle arrest, gene regulation, DNA repair and programmed cell death. As a first step, the DDR includes the recognition of the DNA lesion in the context of the local chromatin landscape followed by activation of signaling cascades and transcriptional programs, depending on the type of DNA damage. Two critical, but as yet poorly understood aspects of the DDR in the plant model, Arabidopsis thaliana, are: (1) the kinetics and regulatory networks controlling the expression of genes orchestrating key biological processes during the DDR and (2) the roles of specific chromatin modifications and chromatin modifying complexes in regulating the process of DNA repair. In the studies comprising my thesis, we worked to shed light on both these knowledge gaps using a combination of genetic, genomic, and biochemical approaches. Chapter one introduces what is currently known about the transcriptional and chromatin-mediated aspects of the DNA damage response, specially focusing on plants. Chapter two presents the development of a temporal model of the Arabidopsis transcriptional response to DNA damage as well as the identification and characterization of key factors that regulate this transcriptional network. Chapter three outlines the setup of a reverse genetic screen to identify candidate chromatin-associated factors required for DNA repair. It also includes the characterization of a candidate chromatin reader, YAF9B, and its homolog YAF9A, in DNA repair. Chapter four concludes by synthesizing the core achievements of the dissertation and suggesting future directions. Together, these chapters have helped understand the multifaceted roles of chromatin in orchestrating DNA repair by revealing the (1) dynamics of transcriptional regulation during the DNA damage response and (2) demonstrating roles for two histone reader proteins, YAF9B and YAF9A, in double strand break repair via homologous recombination-like mechanisms.

Download or read book Chromatin Regulation and Dynamics written by Anita Göndör and published by Academic Press. This book was released on 2016-10-25 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromatin Regulation and Dynamics integrates knowledge on the dynamic regulation of primary chromatin fiber with the 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes. The final chapters discuss the many ways chromatin dynamics can synergize to fundamentally contribute to the development of complex diseases. Chromatin dynamics, which is strategically positioned at the gene-environment interface, is at the core of disease development. As such, Chromatin Regulation and Dynamics, part of the Translational Epigenetics series, facilitates the flow of information between research areas such as chromatin regulation, developmental biology, and epidemiology by focusing on recent findings of the fast-moving field of chromatin regulation. Presents and discusses novel principles of chromatin regulation and dynamics with a cross-disciplinary perspective Promotes crosstalk between basic sciences and their applications in medicine Provides a framework for future studies on complex diseases by integrating various aspects of chromatin biology with cellular metabolic states, with an emphasis on the dynamic nature of chromatin and stochastic principles Integrates knowledge on the dynamic regulation of primary chromatin fiber with 3D nuclear architecture, then connects related processes to circadian regulation of cellular metabolic states, representing a paradigm of adaptation to environmental changes

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 Chromatin written by Ralf Blossey and published by CRC Press. This book was released on 2017-08-04 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: An invaluable resource for computational biologists and researchers from other fields seeking an introduction to the topic, Chromatin: Structure, Dynamics, Regulation offers comprehensive coverage of this dynamic interdisciplinary field, from the basics to the latest research. Computational methods from statistical physics and bioinformatics are detailed whenever possible without lengthy recourse to specialized techniques.

Download or read book Chromatin Dynamics in Cellular Function written by Brehon Laurent and published by Springer. This book was released on 2014-10-19 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume includes timely reviews of several aspects of chromatin biology written by scientists at the forefront of this rapidly moving field. Topics covered include the structure and function of protein modules within chromatin-remodeling proteins, newly characterized histone modifications (methylation, ubiquitylation) and their functional consequences, transcription and histone dynamics, roles of chromatin remodeling factors in DNA replication and repair, and current models of nucleosome-remodeling mechanisms.

Download or read book Chromatin and Disease written by Tapas K. Kundu and published by Springer Science & Business Media. This book was released on 2007-05-04 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book includes a collection of articles with the broad theme of disease connection to chromatin structure and function. It elaborates on the molecular pharmacology of the drugs targeting chromatin structure and its components. The book contains up-to-date information about the chromatin structure and chromatin related diseases and drug functions. This work is the first endeavor to present different aspects encompassing the above theme.

Download or read book Functional Analysis of Chromodomain Helicase DNA Binding Protein 2 Chd2 Mediated Genomic Stability written by Sangeetha Rajagopalan and published by . This book was released on 2010 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt: Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. In this study we demonstrate that mutation of Chd2 renders cells susceptible to inefficient DNA repair and genomic instability. Homozygous and heterozygous Chd2 mutant mouse embryonic fibroblast accumulates higher levels of gamma-H2AX after DNA damage. Chd2 mutant cells show inefficiency in DNA repair of DNA lesions induced by X-rays and UV irradiation as assessed by single cell gel electrophoresis assays. These cells also exhibit increased chromosomal aberrations after treatment with low doses of X-ray irradiation (2 Gy) and show increased radiosensitivity in a clonogenic survival assay. At the molecular level, endogenous CHD2 protein level is induced after exposure to X-ray radiation. In addition, we have also demonstrated in this study that CHD2 is phosphorylated after DNA damage and is a potential substrate for phosphoinositide 3-kinase-related kinases (PIKK) - ATM/ATR. Additionally, mass spectrometric analysis showed possible association of CHD2 with the paraspeckle family of proteins known to be involved in an array of cellular processes specifically in RNA processing and DNA repair. An in vivo splicing assay demonstrated that CHD2 played a role in modulation of pre-mRNA splicing event. Collectively, our findings suggest that CHD2 is a multifunctional protein working with the paraspeckle protein complex to facilitate both the pre-mRNA splicing process and the initial DNA repair process. CHD2 may also be involved in the later stages of DNA damage response pathway by influencing p53's transcriptional activity.

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 Regulation of Nucleosome Dynamics written by Justin Andrew North and published by . This book was released on 2012 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The DNA in eukaryotic cells is organized into a tightly-regulated structural polymer called chromatin that ultimately controls crucial functions of the genome, including gene expression, DNA synthesis, and repair. The basic unit of chromatin is the nucleosome in which 147 base pairs of DNA wraps 1.7-times around eight "core" histone proteins (two copies each of H2A, H2B, H3, H4). Repeats of this structural unit have been shown to fold into higher order structures, which play a central role in controlling DNA accessibility for transcription regulation. However, at the individual nucleosome level, DNA-histone interactions that wrap DNA into the nucleosome also control DNA accessibility. A significant number of factors have been shown to regulate nucleosome accessibility, including variants and post-translational chemical modifications of to the core histone proteins, chromatin remodeling complexes that reposition and disassemble nucleosomes, and histone chaperones that deposit or remove histones. Ultimately, these chromatin regulatory factors must physically alter nucleosomes to change DNA accessibility to transcription, replication, and DNA repair machinery.

Download or read book The Barley Genome written by Nils Stein and published by Springer. This book was released on 2018-08-18 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an overview of the state-of-the-art in barley genome analysis, covering all aspects of sequencing the genome and translating this important information into new knowledge in basic and applied crop plant biology and new tools for research and crop improvement. Unlimited access to a high-quality reference sequence is removing one of the major constraints in basic and applied research. This book summarizes the advanced knowledge of the composition of the barley genome, its genes and the much larger non-coding part of the genome, and how this information facilitates studying the specific characteristics of barley. One of the oldest domesticated crops, barley is the small grain cereal species that is best adapted to the highest altitudes and latitudes, and it exhibits the greatest tolerance to most abiotic stresses. With comprehensive access to the genome sequence, barley’s importance as a genetic model in comparative studies on crop species like wheat, rye, oats and even rice is likely to increase.

Download or read book The Structure and Function of Chromatin written by David W. FitzSimons and published by John Wiley & Sons. This book was released on 2009-09-16 with total page 192 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world.

Download or read book DNA Damage DNA Repair and Disease written by Miral Dizdaroglu and published by Royal Society of Chemistry. This book was released on 2020-11-11 with total page 509 pages. Available in PDF, EPUB and Kindle. Book excerpt: The DNA of all organisms is constantly being damaged by endogenous and exogenous sources. Oxygen metabolism generates reactive species that can damage DNA, proteins and other organic compounds in living cells. Exogenous sources include ionizing and ultraviolet radiations, carcinogenic compounds and environmental toxins among others. The discovery of multiple DNA lesions and DNA repair mechanisms showed the involvement of DNA damage and DNA repair in the pathogenesis of many human diseases, most notably cancer. These books provide a comprehensive overview of the interdisciplinary area of DNA damage and DNA repair, and their relevance to disease pathology. Edited by recognised leaders in the field, this two-volume set is an appealing resource to a variety of readers including chemists, chemical biologists, geneticists, cancer researchers and drug discovery scientists.

Download or read book Gene Regulation Epigenetics and Hormone Signaling written by Subhrangsu S. Mandal and published by John Wiley & Sons. This book was released on 2017-10-23 with total page 678 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first of its kind, this reference gives a comprehensive but concise introduction to epigenetics before covering the many interactions between hormone regulation and epigenetics at all levels. The contents are very well structured with no overlaps between chapters, and each one features supplementary material for use in presentations. Throughout, major emphasis is placed on pathological conditions, aiming at the many physiologists and developmental biologists who are familiar with the importance and mechanisms of hormone regulation but have a limited background in epigenetics.

Download or read book Anatomy of Gene Regulation written by Panagiotis A. Tsonis and published by Cambridge University Press. This book was released on 2003-01-13 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Table of contents

Download or read book Epigenetics Development and Disease written by Tapas Kumar Kundu and published by Springer Science & Business Media. This book was released on 2012-11-13 with total page 698 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book DNA Recombination and Repair written by Paul James Smith and published by Oxford University Press, USA. This book was released on 1999 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: The processes of DNA recombination and repair are vital to cell integrity - an error can lead to disease such as cancer. It is therefore a large and exciting area of research and is also taught on postgraduate and undergraduate courses. This book is not a comprehensive view of the field, but a selection of the issues currently at the forefront of knowledge.