Transcriptional And Chromatin Regulation In Adaptive And Innate Immune Cells
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Transcriptional And Chromatin Regulation In Adaptive And Innate Immune Cells
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Author : Keiko Ozato
language : en
Publisher: Frontiers Media SA
Release Date : 2020-05-22
Transcriptional And Chromatin Regulation In Adaptive And Innate Immune Cells written by Keiko Ozato and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-05-22 with categories.
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.
Chromatin Transcriptional Tango On The Immune Dance Floor
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Author : Ananda L Roy
language : en
Publisher: Frontiers Media SA
Release Date : 2015-04-14
Chromatin Transcriptional Tango On The Immune Dance Floor written by Ananda L Roy and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-04-14 with Chromatin categories.
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.
Chromatin Transcriptional Tango On The Immune Dance Floor
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Author : Ananda L. Roy
language : en
Publisher:
Release Date : 2015
Chromatin Transcriptional Tango On The Immune Dance Floor written by Ananda L. Roy and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with Immunology categories.
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
Chromatin Remodelling And Immunity
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Author :
language : en
Publisher: Academic Press
Release Date : 2017-01-02
Chromatin Remodelling And Immunity written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-01-02 with Medical categories.
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
Transcriptional And Epigenetic Control Of Natural Killer Cells During Viral Infection
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Author : Luke Riggan
language : en
Publisher:
Release Date : 2021
Transcriptional And Epigenetic Control Of Natural Killer Cells During Viral Infection written by Luke Riggan and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
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.
Computational Genomic Analysis Of Transcriptional Regulation In Innate Lymphoid Cell Development
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Author : Herman Gudjonson
language : en
Publisher:
Release Date : 2017
Computational Genomic Analysis Of Transcriptional Regulation In Innate Lymphoid Cell Development written by Herman Gudjonson and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
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.
Molecular Biology Of The Cell
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Author : Bruce Alberts
language : en
Publisher:
Release Date : 2002
Molecular Biology Of The Cell written by Bruce Alberts and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Cytology categories.
Signaling Mechanisms Regulating T Cell Diversity And Function
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Author : Jonathan Soboloff
language : en
Publisher: CRC Press
Release Date : 2017-03-27
Signaling Mechanisms Regulating T Cell Diversity And Function written by Jonathan Soboloff and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-03-27 with Medical categories.
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.
S Adenosylmethionine Dependent Methyltransferases Structures And Functions
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Author : Robert M Blumenthal
language : en
Publisher: World Scientific
Release Date : 1999-07-23
S Adenosylmethionine Dependent Methyltransferases Structures And Functions written by Robert M Blumenthal and has been published by World Scientific this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-07-23 with Science categories.
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.
Interleukin 10 In Health And Disease
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Author : Simon Fillatreau
language : en
Publisher: Springer
Release Date : 2014-07-08
Interleukin 10 In Health And Disease written by Simon Fillatreau and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-08 with Medical categories.
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.