Download or read book Transcriptional and Chromatin Regulation in Adaptive and Innate Immune Cells written by Keiko Ozato and published by Frontiers Media SA. This book was released on 2020-05-22 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transcription depends on an ordered sequence of events, starting with (i) setting of the enhancer and chromatin environment, (ii) assembly of DNA binding and general transcription factors, (iii) initiation, elongation, processing of mRNA and termination, followed by (iv) creation of epigenetic marks and memory formation. Highlighting the importance of these activities, more than 10% total genes are dedicated to regulating transcriptional mechanisms. This area of research is highly active and new insights are continuously being added to our knowledge. Cells of the immune system have unique features of gene regulation to support diverse tasks required for innate and adaptive immunity. Innate immunity involves the recognition of external infectious and noxious agents as well as internal cancer cell components, and the elimination of these agents by non-specific mechanisms. Adaptive immunity involves gene rearrangement to achieve highly specific T and B cell responses, imparting the capability of self and non-self discrimination. This requires transcription and epigenetic regulation. Adaptive immunity also employs epigenetic memory, enabling recapitulation of prior transcription. Recent advances in nuclear architecture, chromatin structure, and transcriptional regulation have provided new insights into immune responses. The increased understanding of these molecular mechanisms is now affording opportunities to improve therapeutic strategies for various diseases.
Download or read book Chromatin Transcriptional Tango on the Immune Dance Floor written by Ananda L Roy and published by Frontiers Media SA. This book was released on 2015-04-14 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt: Signaling through the cell surface antigen receptor is a hallmark of various stages of lymphocyte development and adaptive immunity. Besides the adaptive immune system, the innate immunity is equally important for protection. However, the mechanistic connection between signaling, chromatin changes and downstream transcriptional pathways in both innate and adaptive immune system remains incompletely understood in hematopoiesis. A related issue is how the enhancers communicate to the promoters in a stage specific fashion and in the context of chromatin. Because the factors that regulate chromatin are generally present and active in most cell types, how could cell type and/or stage specific chromatin architecture is achieved in response to a particular immune signal? The genetic loci that encode lymphocyte cell surface receptors are in an ‘unrearranged” or “germline” configuration during the early stages of development. Thus, in addition to expressing lineage and/or stage specific transcription factors during each developmental stage, lymphocytes also need to rearrange their cognate receptor loci in a strictly ordered fashion. Hence, there must be a tightly coordinated communication between the recombination machinery and the transcriptional machinery (including chromatin regulators) at every developmental step. Mature B cells also undergo classswitch recombination and somatic hypermutation. Importantly, along the way, these cells must avoid autoimmune responses and only those cells capable of recognizing foreignantigens are preserved to reach peripheral organs where they must function. The exquisite regulation that govern chromatin accessibility, recombination and transcription regulation in response to the environmental signals in the immune system is discussed here is a series of articles.
Download or read book Chromatin Transcriptional Tango on the Immune Dance Floor written by Ananda L. Roy and published by . This book was released on 2015 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: The process of generating differentiated cell types performing specific effector functions from their respective undifferentiated precursors is dictated by extracellular signals and the recipient cell's ability to transmit those signals to effect changes in cellular functions. One major mechanism for bringing about such changes is at the level of transcription. Thus, inducing transcription of previously silent genes and suppressing active genes in response to the extracellular signal can result in acquiring new functions by the cells. The transcriptional machinery, comprising of RNA Polymerase II and associated general transcription factors, assemble at the core promoter of eukaryotic protein coding genes. The rate and/or stability of formation of this machinery dictate the transcriptional regulation of the corresponding gene, which can be at the level of chromatin regulation as well as enhancer-promoter communication. Such coordinated temporal and spatial regulation of gene expression in response to specific signals determines lineage differentiation, cellular proliferation and development. Every event in the life cycle of a lymphocyte is modulated by the signals they receive. For instance, expression of the B cell antigen receptor (BCR) on the surface of B cells is a hallmark of various stages of B cell development--signaling via the BCR is important both during early/antigen independent (tonic) and late/antigen dependent phases of development. Despite the established requirement for BCR signaling during various phases of B cell maturation, how BCR signaling connects to chromatin changes and downstream transcriptional pathways in each step of development remains poorly understood. Similar questions also remain in other cells of the immune system. Moreover, how the enhancers communicate to the promoters in a stage specific fashion and in the context of chromatin also remain unclear. Chromatin modifiers are generally present and active in most cell types. How could then there be differences in chromatin architecture dependent on a particular stage of development? The B (and T) lymphocytes also perform a unique developmental program because they have an unparalleled genetic makeup--the genetic loci that encode their cell surface receptors are in an 'unrearranged" or "germline" configuration during the early stages of development. Thus, they not only express stage specific genes and transcription factors during each developmental stage, they need to undergo rearrangement of their cognate receptor loci in a strictly ordered fashion to generate a pool of receptor proteins, each capable of recognizing a specific antigen, which they encounter at a much later step. Hence, there must be a strict negotiation between the recombination machinery and the transcriptional machinery at every developmental step of the way. Importantly, along the way, the B cells expressing receptors capable of recognizing self-antigens must be eliminated to avoid autoimmune responses and only those cells capable of recognizing foreign-antigens are preserved to reach peripheral organs where they eventually meet pathogens. How are these processes coordinately regulated in a stage specific fashion and what role does chromatin play? Are the rules of engagement different in innate versus adaptive immune responses? Here we seek to address some of these questions and provide our current understanding of signal-induced chromatin and transcriptional regulation of the immune system
Download or read book Chromatin Remodelling and Immunity written by and published by Academic Press. This book was released on 2017-01-02 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromatin Remodelling and Immunity, Volume 106, the latest release in the Advances in Protein Chemistry and Structural Biology series is an essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics. - Provides cutting-edge developments in protein chemistry and structural biology - Written by authorities in the field - Targeted to a wide audience of researchers, specialists, and students
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Transcriptional Control of Lineage Differentiation in Immune Cells written by Wilfried Ellmeier and published by Springer. This book was released on 2014-09-02 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: Insights into the regulation of immune cell lineage differentiation and specification as well as into the control of lineage integrity, stability and plasticity are of fundamental importance to understanding innate and adaptive immune responses. In this volume, leading experts provide an up-to-date and comprehensive overview of recent advances in the transcriptional control mechanisms and transcription factor networks that regulate these processes in a variety of different immune cell lineages. The chapters cover the regulation of T versus B cell lineage choice, discuss early B cell development and pre-B cell leukemia prevention, address transcriptional control mechanisms during the differentiation, in regulatory T cells and iNKT cells, detail genomic switches in helper cell fate choice and plasticity and highlight the role of the BTB-zinc finger family of transcription factors in T cells. Moreover, the chapters discuss transcriptional networks in DCs, NK cells and in innate lymphoid cells. Together, the reviews illustrate key transcriptional control mechanisms that regulate the development and function of immune cells and demonstrate the impressive advances made over the last decade.
Download or read book Computational Genomic Analysis of Transcriptional Regulation in Innate Lymphoid Cell Development written by Herman Gudjonson and published by . This book was released on 2017 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: Innate lymphoid cells (ILCs) are a recently identified subset of the innate immune system found to have transformative roles in integrating innate and adaptive immune responses. In a wide distribution of tissues, ILCs are important sources of cytokines that promote inflammation, host defense against infection, tissue repair, regulation of microbiota, and physiological homeostasis. As a newly appreciated lineage, many aspects of ILC development and differentiation are not well understood. The Bendelac lab recently identified a common ILC precursor (ILCP) in the fetal liver and bone marrow on the basis of expression of PLZF, the NKT master regulator. The ILCP gives rise to all ILC lineages, including ILC1, ILC2, and ILC3, but not LTi or NK. The developmental stages and associated regulatory factors surrounding the emergence and differentiation of the ILCP have yet to be defined. We present three experimental designs that probe transcriptional regulation in ILC precursors. First we use genome-wide expression profiling to describe the role PLZF plays in distinguishing cNK and ILC1 lineages. Next we performed computational clustering of single ILC progenitor expression profiles to establish a hierarchy of ILC development and found: 1) There is a specific developmental progression of transcription factor induction upstream of the ILCP. 2) ILC differentiation occurs after acquisition of PLZF in the ILCP. 3) LTi specification immediately precedes ILC differentiation and is a distinct lineage decision. 4) ILC differentiation occurs through multilineage transcriptional priming. Finally, we compared chromatin accessibility transcriptional profiling in the ILPC to identify the predominant transcriptional regulators affiliated with ILC specification. The precise elaboration of ILC developmental stages and identification of novel ILC developmental regulators will improve our understanding of the functional requirements of ILCs and their roles in immunity.
Download or read book Chromatin and Transcriptional Regulation in Mouse Macrophages written by Michael McAndrew and published by . This book was released on 2017 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Transcriptional and Epigenetic Control of Natural Killer Cells During Viral Infection written by Luke Riggan and published by . This book was released on 2021 with total page 187 pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural killer (NK) cells are circulating group 1 innate lymphocytes (ILCs) that play a critical role during herpesvirus infection in mice and humans1-3. Although historically categorized as innate immune cells, circulating and tissue-resident group 1 ILCs can exhibit memory responses to mouse cytomegalovirus (MCMV)-associated glycoproteins through expression of germline encoded activating receptors4-6. NK cells possess traits of adaptive immunity, such as memory formation. However, the molecular mechanisms by which NK cells persist to form memory cells are not well understood. In chapter 2, we used single cell RNA sequencing to identify two distinct effector NK cell (NKeff) populations following mouse cytomegalovirus (MCMV) infection. Ly6C- memory precursor NK cells displayed enhanced survival during the contraction phase in a Bcl2-dependent manner, and differentiated into Ly6C+ memory NK cells. MP NK cells exhibited distinct transcriptional and epigenetic signatures compared to Ly6C+ NKeff cells, with a core epigenetic signature shared with MP CD8+ T cells enriched in ETS1 and Fli1 DNA-binding motifs. Until recent years, studying gene function intrinsic to innate immune cell function was limited to Cre-inducible murine models. In order to increase the speed at which we can study gene function, we developed a novel method in Chapter 3 to study gene function in multiple innate immune cell linages during viral infection using a quick and robust protocol. Using this method, we were able to identify Fli1, a transcription factor, which controls memory precursor (MP) Natural Killer cell formation during viral infection. Fli1 was induced by STAT5 signaling ex vivo, and increased Bim levels in early effector NK cells following viral infection. Collectively, these results suggest that a NK cell-intrinsic checkpoint controlled by Fli1 limits MP NK formation by regulating early effector NK cell fitness during viral infection. In addition to transcriptional regulation, NK cells undergo dynamic chromatin remodeling during development and in response to viral infection6,7. However, the epigenetic regulators that are responsible for these genome-wide chromatin changes are unknown. In chapter 4, we identify ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) as a critical regulator of the NK cell regulome. Deletion of UTX in NK cells results in global transcriptional changes and differences in chromatin accessibility at several gene loci involved in NK cell development, homeostasis, and effector function. Together, these results identify UTX as a critical epigenetic regulator of NK cells in mice. In summary, our work has developed a method for studying gene function in innate immune cells, identified novel transcriptional regulation of MP NK cells during memory NK cell formation and profiled epigenetic regulation of NK cell effector function during viral infection.
Download or read book Signaling Mechanisms Regulating T Cell Diversity and Function written by Jonathan Soboloff and published by CRC Press. This book was released on 2017-03-27 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.
Download or read book Interleukin 10 in Health and Disease written by Simon Fillatreau and published by Springer. This book was released on 2014-07-08 with total page 244 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a set of reviews dedicated to the biology of Interleukin (IL)-10. It includes chapters on its importance for maintaining immune homeostasis in humans, its role in intestinal immunity and its functions during viral and bacterial infections. In addition, it presents reviews on the mechanisms linking innate microbial recognition to the production of IL-10 and on how IL-10 recognition by its receptor functions. The roles of T and B cells as relevant sources of IL-10 are also discussed, with an emphasis on the clinical opportunities offered by IL-10-producing Tr1 cells for the suppression of unwanted immunity. Finally, the functions of other cytokines of the IL-10 family are presented. Collectively, these articles provide a comprehensive overview of our current knowledge on one of the most important anti-inflammatory cytokines known to date.
Download or read book S adenosylmethionine dependent Methyltransferases Structures And Functions written by Robert M Blumenthal and published by World Scientific. This book was released on 1999-07-23 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: This invaluable volume, written by an international group of scientists, presents an overview of the AdoMet-dependent methyltransferases, with special emphasis on structure-function relationships.S-adenosyl-L-methionine (AdoMet) is the second most commonly used enzyme cofactor after ATP. The AdoMet-dependent methyltransferases act on a wide variety of target molecules, including DNA, RNA, protein, polysaccharides, lipids and a range of small molecules.The well-conserved architecture of these enzymes, and the implications of this conservation for their evolutionary history, are major themes of this book. The thirteen chapters describe in detail the structures, enzyme kinetics and biological roles of the AdoMet-dependent methyltransferases from a wide range of cell types: plant, animal, bacterial and archaeal.
Download or read book Epigenetics Methods written by Trygve Tollefsbol and published by Academic Press. This book was released on 2020-07-08 with total page 736 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, the field of epigenetics has grown significantly, driving new understanding of human developmental processes and disease expression, as well as advances in diagnostics and therapeutics. As the field of epigenetics continues to grow, methods and technologies have multiplied, resulting in a wide range of approaches and tools researchers might employ. Epigenetics Methods offers comprehensive instruction in methods, protocols, and experimental approaches applied in field of epigenetics. Here, across thirty-five chapters, specialists offer step-by-step overviews of methods used to study various epigenetic mechanisms, as employed in basic and translational research. Leading the reader from fundamental to more advanced methods, the book begins with thorough instruction in DNA methylation techniques and gene or locus-specific methylation analyses, followed by histone modification methods, chromatin evaluation, enzyme analyses of histone methylation, and studies of non-coding RNAs as epigenetic modulators. Recently developed techniques and technologies discussed include single-cell epigenomics, epigenetic editing, computational epigenetics, systems biology epigenetic methods, and forensic epigenetic approaches. Epigenetics methods currently in-development, and their implication for future research, are also considered in-depth. In addition, as with the wider life sciences, reproducibility across experiments, labs, and subdisciplines is a growing issue for epigenetics researchers. This volume provides consensus-driven methods instruction and overviews. Tollefsbol and contributing authors survey the range of existing methods; identify best practices, common themes, and challenges; and bring unity of approach to a diverse and ever-evolving field. Includes contributions by leading international investigators involved in epigenetic research and clinical and therapeutic application Integrates technology and translation with fundamental chapters on epigenetics methods, as well as chapters on more novel and advanced epigenetics methods Written at verbal and technical levels that can be understood by scientists and students alike Includes chapters on state-of-the-art techniques such as single-cell epigenomics, use of CRISPR/Cas9 for epigenetic editing, and epigenetics methods applied to forensics
Download or read book Protein Kinase mediated Decisions Between Life and Death written by Ayse Basak Engin and published by Springer Nature. This book was released on 2021-02-04 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein phosphorylation via protein kinases is an inevitable process that alters physiological and pathological functions of the cells. Thus, protein kinases play key roles in the regulation of cell life or death decisions. Protein kinases are frequently a driving factor in a variety of human diseases including aging and cellular senescence, immune system and endothelial dysfunctions, cancers, insulin resistance, cholestasis and neurodegenerative diseases, as well as bacterial resistance in persistent infections. Recent developments in quantitative proteomics provide important opinions on kinase inhibitor selectivity and their modes of action in the biological context. Protein Kinase-mediated Decisions Between Life and Death aims to have the reader catch insights about up-to-date opinions on “Protein Kinases” related pathways that threaten human health and life. As “Protein Kinases” are related to many health problems, clinicians, basic science researchers and students need this information. Chapter “Signal Transduction in Immune Cells and Protein Kinases” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Download or read book Regulation of Cancer Immune Checkpoints written by and published by . This book was released on 2020 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.
Download or read book Regulation of Cytokine Gene Expression in Immunity and Diseases written by Xiaojing Ma and published by Springer. This book was released on 2016-10-12 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book explores the major cytokines, such as IL-1 and IFN-γ, with respect to the regulation of their gene expression and protein production in specific immune cell types. It discusses both healthy physiological settings and in pathological situations in which the expression of some cytokines could be dysregulated, resulting in either immunodeficiency or exacerbated inflammatory sequelae in animal models as well as in human patients. Cytokines are important regulators of immune responses that require the highly coordinated participation and communication of multiple cell types. The expression of cytokines by various producer cell types is therefore carefully regulated in response to environmental cues at multiple levels: transcription, translation and posttranslational modification. Presenting cutting-edge advances in our understanding of the regulation of cytokine expression, this book is a valuable resource for anyone involved or interested in immune regulation.
Download or read book Toll Like Receptors TLRs and Innate Immunity written by Stefan Bauer and published by Springer Science & Business Media. This book was released on 2007-12-11 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.
