Investigating the Role of the Nucleosome Remodeling Factor INO80 in Development and NURF in Anti-tumor Immunity PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Investigating the Role of the Nucleosome Remodeling Factor INO80 in Development and NURF in Anti-tumor Immunity PDF full book. Access full book title Investigating the Role of the Nucleosome Remodeling Factor INO80 in Development and NURF in Anti-tumor Immunity by Zeinab Elsayed. Download full books in PDF and EPUB format.
Author: Zeinab Elsayed
Publisher:
ISBN:
Category :
Languages : en
Pages : 150
Get Book Here
Book Description
Understanding how an epigenetic regulator such as ATP-dependent chromatin-remodeling complexes modulate processes such as development and/or immune response is essential for our comprehension of cell biology. Deletion of the ATP-dependent chromatin remodeling factor INO80 is known to be embryonically lethal, however, the mechanism is not known. To identify roles for INO80 in mouse early development we generated Ino80 KO mice. Ino80 KO ESCs (Embryonic stem cells) were viable when maintained at ground state pluripotency but fail to differentiate in vitro and in vivo. Gene expression analysis of Ino80 KO early embryos by in situ hybridization showed elevated Bmp4 expression and reduced expression of DVE (distal visceral endoderm) markers Cer1, Hex, and Lefty1. BMP4 is a known negative regulator of DVE differentiation in the early embryo. Molecular studies in Ino80 KO ESCs demonstrated that INO80 is bound to the Bmp4 promoter, and regulates its chromatin structure, to suppress the positive regulator SP1 from stimulating its transcription. These results, suggest that INO80 directly regulates the chromatin structure of the Bmp4 promoter with consequences to mouse embryo development. These results are significant because they demonstrate a specific role of INO80 in establishing P-D embryonic axis. NURF (Nucleosome remodeling factor) is another ATP-dependent chromatin remodeling complex that is overexpressed in many cancer types including breast cancer. To demonstrate the roles of NURF in breast cancer biology, we knocked-down the NURF essential subunit BPTF (bromodomain PHD finger transcription factor) in mouse breast cancer cell lines. Transplantation of these cell lines into immune-competent mice revealed that BPTF KD enhances NK cell antitumor activity. BPTF KD enhanced NK-92 cytotoxic activity toward BPTF KD cells by NKp30 activation in vitro. NK-92 activity is reduced by the addition of heparin to the culture medium, further indicating the involvement of NKp30 (in human) and NCR1 (in mice) in killing of tumor cells. We found that BPTF controls the abundance of NKp30/NCR1 ligands (heparin sulfate proteoglycans (HSPGs) by regulation of heparanase expression (endoglycosidase that degrades HSPGs). In addition, BPTF depletion in established mouse breast tumors enhanced anti-tumor immunity, without affecting NK or T cell cytotoxic activity, providing a novel immunotherapy target.
Author: Zeinab Elsayed
Publisher:
ISBN:
Category :
Languages : en
Pages : 150
Get Book Here
Book Description
Understanding how an epigenetic regulator such as ATP-dependent chromatin-remodeling complexes modulate processes such as development and/or immune response is essential for our comprehension of cell biology. Deletion of the ATP-dependent chromatin remodeling factor INO80 is known to be embryonically lethal, however, the mechanism is not known. To identify roles for INO80 in mouse early development we generated Ino80 KO mice. Ino80 KO ESCs (Embryonic stem cells) were viable when maintained at ground state pluripotency but fail to differentiate in vitro and in vivo. Gene expression analysis of Ino80 KO early embryos by in situ hybridization showed elevated Bmp4 expression and reduced expression of DVE (distal visceral endoderm) markers Cer1, Hex, and Lefty1. BMP4 is a known negative regulator of DVE differentiation in the early embryo. Molecular studies in Ino80 KO ESCs demonstrated that INO80 is bound to the Bmp4 promoter, and regulates its chromatin structure, to suppress the positive regulator SP1 from stimulating its transcription. These results, suggest that INO80 directly regulates the chromatin structure of the Bmp4 promoter with consequences to mouse embryo development. These results are significant because they demonstrate a specific role of INO80 in establishing P-D embryonic axis. NURF (Nucleosome remodeling factor) is another ATP-dependent chromatin remodeling complex that is overexpressed in many cancer types including breast cancer. To demonstrate the roles of NURF in breast cancer biology, we knocked-down the NURF essential subunit BPTF (bromodomain PHD finger transcription factor) in mouse breast cancer cell lines. Transplantation of these cell lines into immune-competent mice revealed that BPTF KD enhances NK cell antitumor activity. BPTF KD enhanced NK-92 cytotoxic activity toward BPTF KD cells by NKp30 activation in vitro. NK-92 activity is reduced by the addition of heparin to the culture medium, further indicating the involvement of NKp30 (in human) and NCR1 (in mice) in killing of tumor cells. We found that BPTF controls the abundance of NKp30/NCR1 ligands (heparin sulfate proteoglycans (HSPGs) by regulation of heparanase expression (endoglycosidase that degrades HSPGs). In addition, BPTF depletion in established mouse breast tumors enhanced anti-tumor immunity, without affecting NK or T cell cytotoxic activity, providing a novel immunotherapy target.
Author: Aiman S. Alhazmi
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
The nucleosome remodeling factor (NURF) is an evolutionary conserved ATP-dependent chromatin remodeling factor. It was first isolated from Drosophila as a complex with enzymatic activity that once recruited to nucleosome, it slides the nucleosome to provide accessibility for transcription factors. Since then, numerous works from animal models and cell lines show the role of NURF as a regulator of gene expression. NURF interacts with H3K4me3 and sequence specific transcription factors that recruit the complex to promoter regions. Whether this is the only mechanism by which NURF regulates gene expression is not known. However, other ATP-dependent chromatin remodeling complexes are known to regulate gene expression independent from transcription initiation. In order to explore the role of NURF in regulating gene expression, we utilized two genome wide approaches to map NURF binding and NURF dependent changes in chromatin structure using ChIP-Seq and FAIRE-Seq, respectively. From these analyses, we discovered that NURF broadly localizes in the genome with preferences to gene bodies and 3'ends of genes. Also, we found that NURF maintains open chromatin regions at upstream, intron and downstream of genes. These novel findings shed light on new roles for NURF complex within genes, in addition to its classical role at promoter regions. Furthermore, we discovered the function of a previously uncharacterized domain in the NURF specific subunit BPTF. We show that the N-terminal the plant homeodomain (PHD) of BPTF directly interacts with THOC4, a protein associated with RNA-pol 2. Also, we show using ChIP analyses that this interaction recruits BPTF to gene bodies. Next, we investigated functional consequences for NURF recruitment to gene bodies using Cyclin D1 (Ccnd1) gene as a model. These analyses revealed that NURF is required for normal mRNA processing and loss of NURF induces intron retention, which results in unstable transcripts. Finally, we show that the defect in mRNA processing is not specific to the Ccnd1 gene, as we observe similar defects in four other BPTF dependent genes. Together, our work uncovered new role of mammalian NURF complex in regulating gene expression through mRNA processing.
Author: Renato Paro
Publisher: Springer Nature
ISBN: 3030686701
Category : Science
Languages : en
Pages : 215
Get Book Here
Book Description
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: Tapas K. Kundu
Publisher: Springer Science & Business Media
ISBN: 1402054661
Category : Science
Languages : en
Pages : 456
Get Book Here
Book Description
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.
Author: Fumio Hanaoka
Publisher: Springer
ISBN: 443155873X
Category : Science
Languages : en
Pages : 548
Get Book Here
Book Description
This book is a comprehensive review of the detailed molecular mechanisms of and functional crosstalk among the replication, recombination, and repair of DNA (collectively called the "3Rs") and the related processes, with special consciousness of their biological and clinical consequences. The 3Rs are fundamental molecular mechanisms for organisms to maintain and sometimes intentionally alter genetic information. DNA replication, recombination, and repair, individually, have been important subjects of molecular biology since its emergence, but we have recently become aware that the 3Rs are actually much more intimately related to one another than we used to realize. Furthermore, the 3R research fields have been growing even more interdisciplinary, with better understanding of molecular mechanisms underlying other important processes, such as chromosome structures and functions, cell cycle and checkpoints, transcriptional and epigenetic regulation, and so on. This book comprises 7 parts and 21 chapters: Part 1 (Chapters 1–3), DNA Replication; Part 2 (Chapters 4–6), DNA Recombination; Part 3 (Chapters 7–9), DNA Repair; Part 4 (Chapters 10–13), Genome Instability and Mutagenesis; Part 5 (Chapters 14–15), Chromosome Dynamics and Functions; Part 6 (Chapters 16–18), Cell Cycle and Checkpoints; Part 7 (Chapters 19–21), Interplay with Transcription and Epigenetic Regulation. This volume should attract the great interest of graduate students, postdoctoral fellows, and senior scientists in broad research fields of basic molecular biology, not only the core 3Rs, but also the various related fields (chromosome, cell cycle, transcription, epigenetics, and similar areas). Additionally, researchers in neurological sciences, developmental biology, immunology, evolutionary biology, and many other fields will find this book valuable.
Author: Nagwa El-Badri
Publisher: Springer Nature
ISBN: 3030553590
Category : Medical
Languages : en
Pages : 374
Get Book Here
Book Description
This textbook covers the basic aspects of stem cell research and applications in regenerative medicine. Each chapter includes a didactic component and a practical section. The book offers readers insights into: How to identify the basic concepts of stem cell biology and the molecular regulation of pluripotency and stem cell development. How to produce induced pluripotent stem cells (iPSCs) and the basics of transfection. The biology of adult stem cells, with particular emphasis on mesenchymal stromal cells and hematopoietic stem cells, and the basic mechanisms that regulate them. How cancer stem cells arise and metastasize, and their properties. How to develop the skills needed to isolate, differentiate and characterize adult stem The clinical significance of stem cell research and the potential problems that need to be overcome. Evaluating the use of stem cells for tissue engineering and therapies (the amniotic membrane) The applications of bio-nanotechnology in stem cell research. How epigenetic mechanisms, including various DNA modifications and histone dynamics, are involved in regulating the potentiality and differentiation of stem cells. The scientific methods, ethical considerations and implications of stem cell research.
Author: Carsten Carlberg
Publisher: Springer
ISBN: 9811076146
Category : Medical
Languages : en
Pages : 234
Get Book Here
Book Description
The term epigenetics describes regulatory and information storing mechanisms of specific genes that do not involve any change of their DNA sequence. Epigenetics is closely related to the extensively folded state, in which the genome is packaged, known as chromatin. New genomic tools nowadays allow the genome-wide assessment of, for example, chromatin states and DNA modifications, and led to the discovery of unexpected new epigenetic principles, such as epigenomic memory. This was the start of the field of epigenomics, the relation of which to human health and disease is discussed in this textbook. This book aims to summarize, in a condensed form, the role of epigenomics in defining chromatin states that are representative of active genes (euchromatin) and repressed genes (heterochromatin). Moreover, this book discusses the principles of gene regulation, chromatin stability, genomic imprinting and the reversibility of DNA methylation and histone modifications. This information should enable a better understanding of cell type identities and will provide new directions for studies of, for example, cellular reprograming, the response of chromatin to environmental signals and epigenetic therapies that can improve or restore human health. In order to facilitate the latter, we favor a high figure-to-text ratio following the rule “a picture tells more than thousand words”. The content of the book is based on the lecture course “Molecular Medicine and Genetics” that is given by one of us (C. Carlberg) in different forms since 2002 at the University of Eastern Finland in Kuopio. Thematically, this book is located between our textbooks “Mechanisms of Gene Regulation” (ISBN 978-94-017-7741-4) and “Nutrigenomics” (ISBN 978-3-319-30415-1), studying of which may also be interesting to our readers. The book is sub-divided into three sections and 13 chapters. Following the Introduction (section A), section B will explain the molecular basis of epigenomics, while section C will provide examples for the impact of epigenomics in human health and disease. The lecture course is primarily designed for Master level students of biomedicine, but is also frequented by PhD students as well as by students of other bioscience disciplines. Besides its value as a textbook, Human Epigenomics will be a useful reference for individuals working in biomedicine.
Author: Jerry L. Workman
Publisher: Springer Science & Business Media
ISBN: 1461486246
Category : Medical
Languages : en
Pages : 594
Get Book Here
Book Description
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.
Author: Pramod C. Rath
Publisher: Springer
ISBN: 9789811021541
Category : Medical
Languages : en
Pages : 0
Get Book Here
Book Description
This book presents a collection of articles on various aspects of current research on aging. These include model systems, cellular, biochemical and molecular aspects of experimental aging research, as well as selected intervention studies on age-related diseases. Aging is a global challenge to human society. Children are always in a hurry to become adults, while adults produce offspring and add to the gene pool. However, after adulthood or the attainment of reproductive maturity, all physiological parameters of the living organism start to undergo the aging process. Old age sets in slowly but surely, and usually continues for a prolonged period. If vigor and vitality are the main advantages of adulthood, old age offers the rewards of experience and maturity. Biologists ask questions such as: Why do we age? How do we become old? Is it possible to slow down, postpone or even prevent aging? In turn, medical experts ask: What are the diseases associated with old age? Are there medicines that can help affected elderly patients? In fact both groups are asking themselves how can we add more health to old age. Healthy aging is the dream of every individual. But to achieve this, it is fundamental that we first understand the cellular, biochemical and molecular basis of the aging process in mammalian cells, tissues and intact living organisms, which can serve as experimental model systems in Biomedical Gerontology. Once the biology of aging is understood at the genetic and molecular levels, interventional approaches to aging and its associated diseases may be easier to plan and implement at the preclinical level.
Author: Horst Feldmann
Publisher: John Wiley & Sons
ISBN: 3527644865
Category : Science
Languages : en
Pages : 349
Get Book Here
Book Description
Yeast is one of the oldest domesticated organisms and has both industrial and domestic applications. In addition, it is very widely used as a eukaryotic model organism in biological research and has offered valuable knowledge of genetics and basic cellular processes. In fact, studies in yeast have offered insight in mechanisms underlying ageing and diseases such as Alzheimers, Parkinsons and cancer. Yeast is also widely used in the lab as a tool for many technologies such as two-hybrid analysis, high throughput protein purification and localization and gene expression profiling. The broad range of uses and applications of this organism undoubtedly shows that it is invalubale in research, technology and industry. Written by one of the world's experts in yeast, this book offers insight in yeast biology and its use in studying cellular mechanisms.
