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  • 1
    Keywords: Medicine ; Oncology ; Human Genetics ; Biomedicine ; Human Genetics ; Cancer Research ; Springer eBooks
    Description / Table of Contents: Preface -- Introduction -- Non-mammalian hematopoiesis -- Epigenetic mechanisms regulating mammalian hematopoietic stem cell development and function -- Epigenetic and transcriptional mechanisms regulating cell fate decisions and blood cell lineage development -- Epigenetic control of immune cell function -- Subject index
    Abstract: In recent years, great progress has been made in the identification of the molecular players involved in the epigenetic control of gene expression during development. The work of many laboratories has established that regulating the interplay of transcription factors with chromatin components is the major driver of cellular differentiation. Because of their single cell nature and ease of purification, much of what we have learnt about these processes in animals has been delivered based on cellular models within the hematopoietic system. The blood cell system evolved from a few simple cell types in more primitive organisms that provide oxygen transport and carry out phagocytosis into the complex hematopoietic system of mammals, containing many specialized cells types with vastly different functions, such as B cells, T cells, granulocytes, macrophages, erythrocytes, and megakaryocytes. This book describes the intricate processes involved in the development of blood cells across a range of organisms from drosophila and fish at one end, and mammals at the other end. It contains individual chapters devoted to describing the epigenetic and transcriptional mechanisms regulating hematopoiesis in the different organisms and orchestrating the differentiation of a wide variety of cell types. Different chapters describe the function of lymphocytes, macrophages and red blood cells and the molecular players, i.e. transcription factors and the epigenetic regulatory machinery driving their differentiation. Most importantly, the book not only describes normal processes, such as the rearrangements of antigen receptor genes, and the regulation of genes by various mechanisms such as DNA methylation, but also outlines what happens when these processes function abnormally to precipitate diseases such as leukemia and immune disorders
    Pages: XIII, 416 p. 49 illus. in color. : online resource.
    ISBN: 9783642451980
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  • 2
    ISSN: 0730-2312
    Keywords: chicken lysozyme gene ; loop organization of chromatin ; locus control region ; locus boundary element ; position independent expression ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are performed in order to investigate the functional relevance of this structural subdivision of eukaryotic chromatin for the control of gene expression. We used the chicken lysozyme gene locus as a model to examine the relation between chromatin structure and gene function. Several structural features of the lysozyme locus are known: the extension of the region of general DNAasel sensitivity of the active gene, the location of DNA-sequences with high affinity for the nuclear matrix in vitro, and the position of DNAasel hypersensitive chromatin sites (DHSs). The pattern of DHSs changes depending on the transcriptional status of the gene. Functional studies demonstrated that DHSs mark the position of cis-acting regulatory elements. Additionally, we discovered a novel cis-activity of the border regions of the DNAasel sensitive domain (A-elements). By eliminating the position effect on gene expression usually observed when genes are randomly integrated into the genome after transfection, A-elements possibly serve as punctuation marks for a regulatory chromatin domain. Experiments using transgenic mice confirmed that the complete structurally defined lysozyme gene domain behaves as an independent regulatory unit, expressing the gene in a tissue specific and position independent manner. These expression features were lost in transgenic mice carrying a construct, in which the A-elements as well as an upstream enhancer region were deleted, indicating the lack of a locus activation function on this construct. Experiments are designed in order to uncover possible hierarchical relationships between the different cis-acting regulatory elements for stepwise gene activation during cell differentiation. We are aiming at the definition of the basic structural and functional requirements for position independent and high level gene expression. The result of these experiments will have important consequences for random gene transfer with predictable and reproducible expression of transgenes.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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