Polycomb Group Proteins is a comprehensive volume detailing the mechanisms that are key to the management of genome function in many different contexts, from embryonic stem cells to terminal differentiation. The book discusses the regulation of cell lineages, cell proliferation, apoptosis, X chromosome inactivation, and most major genome programming choices. In the last few years, the biochemical understanding of PRC1-type complexes has greatly expanded in terms of the number of components involved and the intricacies of their interactions. The functionalities of these various complexes and their components are not all well understood, but recent work has shown an important division of labor and roles in the recruitment of stable binding in the ability to lay the groundwork of histone modifications and in the epigenetic maintenance of repressed states. In an effort to provide clarity in this topical research area, the book provides a cluster of chapters that deal with variant PRC1 complexes, their taxonomy, their components, their interactions, and what is known of their functions. Provides topical coverage on accessory components that are known to be involved in PcG recruitment in Drosophila and their less understood role in mammals Includes dedicated sections on PRC1 complexes and PRC2 complexes for quick reference Features the role of RNA molecules in different aspects of Polycomb proteins involvement in epigenetic regulation, beginning with the key role of the Xist RNA in recruiting and spreading PcG complexes on the inactive X chromosome
|Author||: Claudia Gentile|
|Release Date||: 2019|
|Pages||: 329 pages|
"Proper embryonic development requires the function of the Hox gene family, which encode transcription factors essential for patterning the developing embryo along its main body axis. Most remarkably, the Hox genes are expressed in a spatially- and temporally- collinear fashion, corresponding to their relative positions along the chromosome. As such, mechanisms for Hox gene activation have been largely studied as the deregulation of Hox genes leads to severe developmental malformations. Our lab uses the developing limb as a model system to study Hox gene regulation. Previous work in our lab as well as others has contributed to understanding mechanisms of Hox gene activation through the identification of numerous enhancer elements which are located outside of the HoxA and HoxD clusters, within the large regulatory landscapes that flank the clusters. However, mechanisms for Hox gene silencing still remain largely elusive. Studies have demonstrated the important role for the Polycomb Group (PcG) protein complexes in the transcriptional repression of the Hox genes during development. Therefore, the aim of my thesis was to study the functional role of the PcG proteins in HoxA gene regulation during limb development. We first studied the functional role of the PcG proteins in organizing the chromatin architecture at and around the HoxA cluster. ChIP-seq experiments to map the binding of the Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2) in the proximal and distal limb bud at embryonic day 12.5 (E12.5) revealed that PcG occupancy correlated with the dynamic expression of the HoxA genes in the proximal and distal limb. Moreover, to study the functional link between PcG occupancy and chromatin organization we performed 5C (Chromosome Conformation Capture Carbon Copy), which allows for the detection of long-range spatial interactions between two genomic loci of interest. Our 5C analyses revealed that PcG bound loci physically interact in the 3D-environment, and that these contacts are lost upon PRC2 inactivation. In addition, we show that the differences in chromatin architecture which distinguish the proximal from distal limb were abrogated upon loss of PRC2 function. The resulting changes in chromatin architecture demonstrate that PRC2 is required to prevent certain enhancer-promoter interactions in the proximal limb in order to maintain Hoxa13 gene repression, whereas unexpectedly, we also find that PRC2 function is required to favor other enhancer-promoter contacts needed for HoxA gene activation by modulating the chromatin organization via PcG-mediated long-range contacts. Next, we assessed the genome-wide binding dynamics of PRC1 and PRC2 during limb development and demonstrated the requirement of PRC2 for transcriptional regulation. Our analyses revealed that PRC1 and PRC2 target genes involved in developmental processes and that the inactivation of PRC2 results in an up-regulation of these target genes. Strikingly, our analyses also reveal that PRC1 occupancy is unaffected by PRC2 inactivation, which reveals that a complex functional relationship between PRC1 and PRC2 exists during development. Finally, we show that while PRC2 inactivation does not globally affect proximal and distal limb identity, PRC2 is necessary to maintain the proper Hox transcriptional programs in the proximal and distal limb. Altogether this work emphasizes the important role of PcG proteins in regulating Hox gene expression during limb development. Importantly, we identified the contribution of PcG proteins in modulating the chromatin architecture at the HoxA cluster to promote gene activation and silencing. Moreover, we uncovered a dynamic relationship between PRC1 and PRC2 occupancy on a genome-wide scale, which correlates to transcriptional regulation during limb development. Overall, this work provides insights into the complex relationship between gene activation and repression during development processes"--
|Author||: Julia Bammer|
|Release Date||: 2018|
|Pages||: 329 pages|
|Author||: Nicole Schönrock|
|Release Date||: 2006|
|Pages||: 220 pages|
|Author||: Toshio Nakanishi,Roger R. Markwald,H.Scott Baldwin,Bradley B. Keller,Deepak Srivastava,Hiroyuki Yamagishi|
|Release Date||: 2016-06-24|
|ISBN 10||: 4431546286|
|Pages||: 383 pages|
This volume focuses on the etiology and morphogenesis of congenital heart diseases. It reviews in detail the early development and differentiation of the heart, and later morphologic events of the cardiovascular system, covering a wide range of topics such as gene functions, growth factors, transcription factors and cellular interactions that are implicated in cardiac morphogenesis and congenital heart disease. This book also presents recent advances in stem cell and cell sheet tissue engineering technologies which have the potential to provide novel in vitro disease models and to generate regenerative paradigms for cardiac repair and regeneration. This is the ideal resource for physician scientists and investigators looking for updates on recent investigations on the origins of congenital heart disease and potential future therapies.
|Author||: Breanne Danielle White Karanikolas|
|Release Date||: 2008|
|Pages||: 296 pages|
Epigenetic Gene Expression and Regulation reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies. The book shows how these heritable mechanisms allow individual cells to establish stable and unique patterns of gene expression that can be passed through cell divisions without DNA mutations, thereby establishing how different heritable patterns of gene regulation control cell differentiation and organogenesis, resulting in a distinct human organism with a variety of differing cellular functions and tissues. The work begins with basic biology, encompasses methods, cellular and tissue organization, topical issues in epigenetic evolution and environmental epigenesis, and lastly clinical disease discovery and treatment. Each highly illustrated chapter is organized to briefly summarize current research, provide appropriate pedagogical guidance, pertinent methods, relevant model organisms, and clinical examples. Reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies Helps readers understand how epigenetic marks are targeted, and to what extent transgenerational epigenetic changes are instilled and possibly passed onto offspring Chapters are replete with clinical examples to empower the basic biology with translational significance Offers more than 100 illustrations to distill key concepts and decipher complex science
Handbook of Epigenetics: The New Molecular and Medical Genetics, Second Edition, provides a comprehensive analysis of epigenetics, from basic biology, to clinical application. Epigenetics is considered by many to be the new genetics in that many biological phenomena are controlled, not through gene mutations, but rather through reversible and heritable epigenetic processes. These epigenetic processes range from DNA methylation to prions. The biological processes impacted by epigenetics are vast and encompass effects in lower organisms and humans that include tissue and organ regeneration, X-chromosome inactivation, stem cell differentiation, genomic imprinting, and aging. The first edition of this important work received excellent reviews; the second edition continues its comprehensive coverage adding more current research and new topics based on customer and reader reviews, including new discoveries, approved therapeutics, and clinical trials. From molecular mechanisms and epigenetic technology, to discoveries in human disease and clinical epigenetics, the nature and applications of the science is presented for those with interests ranging from the fundamental basis of epigenetics, to therapeutic interventions for epigenetic-based disorders. Timely and comprehensive collection of fully up-to-date reviews on epigenetics that are organized into one volume and written by leading figures in the field Covers the latest advances in many different areas of epigenetics, ranging from basic aspects, to technologies, to clinical medicine Written at a verbal and technical level that can be understood by scientists and college students Updated to include new epigenetic discoveries, newly approved therapeutics, and clinical trials
Puberty is a unique paradigm for the understanding of gene-environment interaction and developmental programming. Therefore, normal and abnormal pubertal development can be divided and examined in three sections: the role of genetic factors, the role of environmental factors (including nutrition) and therapeutic issues in disorders of puberty. Dealing with all of these sections and framed along current key concepts in pediatric endocrinology, experts share their view on critical issues such as weighting of genetic versus environmental factors or the impact of environmental factors in relation to critical periods in development. Not only showing the consensus and controversial issues in the various areas, each chapter presents lessons for clinical management in an attempt to link basic research, physiology and pathophysiology with the clinical management of pubertal disorders. Puberty from Bench to Clinic bridges up-to-date concepts from animal and human physiology and pathology towards a better understanding and management of pubertal disorders, making it a unique resource for researchers in the field of development and reproduction, clinical scientists and practitioners in neuro-, pediatric and adolescent endocrinology as well as gynecology.
In recent years new discoveries have made this an exciting and important field of research. This exhaustive volume presents comprehensive chapters and detailed background information for researchers working with in the field of nuclear mechanics and genome regulation. Both classic and state-of-the-art methods readily adaptable and designed to last the test of time Relevant to clinicians and scientists working in a wide range of fields
More than two thirds of all living organisms described to date belong to the phylum Arthropoda. But their diversity, as measured in terms of species number, is also accompanied by an amazing disparity in terms of body form, developmental processes, and adaptations to every inhabitable place on Earth, from the deepest marine abysses to the earth surface and the air. The Arthropoda also include one of the most fashionable and extensively studied of all model organisms, the fruit-fly, whose name is not only linked forever to Mendelian and population genetics, but has more recently come back to centre stage as one of the most important and more extensively investigated models in developmental genetics. This approach has completely changed our appreciation of some of the most characteristic traits of arthropods as are the origin and evolution of segments, their regional and individual specialization, and the origin and evolution of the appendages. At approximately the same time as developmental genetics was eventually turning into the major agent in the birth of evolutionary developmental biology (evo-devo), molecular phylogenetics was challenging the traditional views on arthropod phylogeny, including the relationships among the four major groups: insects, crustaceans, myriapods, and chelicerates. In the meantime, palaeontology was revealing an amazing number of extinct forms that on the one side have contributed to a radical revisitation of arthropod phylogeny, but on the other have provided evidence of a previously unexpected disparity of arthropod and arthropod-like forms that often challenge a clear-cut delimitation of the phylum.
During the past few decades, it has become increasingly apparent that heredity is not the sole determining factor in disease development, such as cancer. This landmark work covers a wide array of aspects in the relatively new area of epigenetics, ranging from its role in the basic mechanisms of tumorigenesis, to the newest epigenetic drugs being developed and used for cancer therapy. Cancer Epigenetics presents in-depth discussions of DNA methylation alterations, histone and RNA modifications, and nucleosome remodeling, which are all intimately involved in the formation of tumors. It also analyzes metabolic influences on cancer epigenetics and advances in epigenetic cancer gene therapy. Discusses the Latest Advances in the Role of Epigenetics in Tumor Initiation, Progression, and Metastasis With stand-alone chapters written by research pioneers in the field, this definitive resource covers— DNA methylation and cancer Histone modifications in cancer Emerging areas of cancer epigenetics Epigenetics in the diagnosis, prognosis, and therapy of cancer Future directions in epigenetic cancer research Bringing together different topics into a single compilation, this text is a prime resource for those with interests ranging from the basic mechanisms of tumor biology to cancer therapy. It also serves as a core textbook for advanced courses with a focus on genetic diseases, molecular biology, and/or cancer. This seminal work answers the call for a thorough and authoritative reference that covers the critical and contemporary aspects of this revolutionary field.