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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.
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.
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.
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.
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.
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
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.
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.