Download or read book Transcription factors in blood cell development written by Tilman Borggrefe and published by Springer Nature. This book was released on with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Transcription Factors written by Katya Ravid and published by John Wiley & Sons. This book was released on 2003-11-04 with total page 640 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transcription Factors Normal and Malignant Development of Blood Cells Katya Ravid and Jonathan Licht The role of transcription factors in activating specific genes in blood cells is an important facet of hematopoiesis. Equally important, however, is the pursuit of genes rearranged and aberrantly activated in leukemias (blood malignancies). Transcription Factors: Normal and Malignant Development of Blood Cells focuses on those major transcription factors involved in activation of lineage-specific gene expression during normal versus malignant development of specific blood lineages, as revealed from gene promoter studies, knockout of transcription factors in mice models, and the identification and characterization of chromosomal rearrangement in human blood leukemias. This complete digest of current transcription factor data offers comprehensive coverage of the myriad of transcription factors in blood cell development, composed by established experts in the field. In addition to updating the reader on the connection between chromosomal translocations involving transcription factors and cellular transformation leading to leukemia, Transcription Factors also reviews such subjects as: * Transcription factors and the megakaryocytic, myeloid, and erythroid lineages * Leukemias due to chromosomal translocations involving gene encoding transcription factors * Oncogenesis and hematopoiesis * In vivo studies of transcription factors implicated in hematopoiesis * And much more Appealing to both the researcher and the clinician in the field of hematology, Transcription Factors is a timely presentation of cell lineage development and sheds light on the processes involved in the development of specific leukemias. Providing insight into the study of transcription factors, readers will gain an understanding of mechanisms that lead to normal lineage commitment and terminal differentiation.

Download or read book Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development written by Constanze Bonifer and published by Springer Science & Business Media. This book was released on 2014-03-12 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: During vertebrate hematopoiesis many specialized cell types are formed with vastly different functions such as B cells, T cells, granulocytes, macrophages, erythrocytes and megakaryocytes. To tightly control the enormous proliferative potential of developing blood cells, an intricately balanced signaling and transcription network has evolved that ensures that the different cell types are formed at the right time and in the right numbers. Intricate regulatory mechanisms ensure that blood cells function properly and have a determined life span. Moreover, in the adaptive immune system, long-lived memory cells have evolved that ensure that when pathogens have been seen once they will never cause a problem again. In this book we will therefore make a journey from asking how more primitive organisms use the epigenetic regulatory machinery to balance growth with differentiation control towards digging deep into what controls the function of specialized cells of the human immune system. We will first discover that flies make blood but exist without blood vessels, why fish make blood cells in the kidney and which precise genetic circuitries are required for these developmental pathways. We will then learn the regulatory principles that drive the differentiation of mature blood cells from stem cells and what controls their function in mammals. In the process, we will find out what unites hematopoietic stem cells and endothelial cells. Finally, we will shed light on the molecular mechanisms that either alter hematopoietic cell differentiation or lead to the development of cells with impaired function.

Download or read book Regulation of Lozenge Transcription Factor Activity and Blood Cell Development by MLF and Its Partner DnaJ 1 written by Aichun Chen and published by . This book was released on 2017 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hematopoiesis is the process of formation of fully differentiated blood cells from hematopoietic stem cells (HSCs). This process is tightly controlled by the integration of developmental and homeostatic signals to ensure the generation of an appropriate number of each blood cell type. At the molecular level, the regulation of this developmental process is mediated by a number of transcription factors, especially by members of the RUNX family, and mutations affecting these factors are at the origin of numerous hemopathies, including leukemia. Intriguingly, many transcriptional regulators and signaling pathways controlling blood cell development are evolutionarily conserved from humans to Drosophila melanogaster. Hence, the fruit fly has become a potent and simplified model to study the mechanisms underlying the specification of blood cell lineages and the regulation of blood cell homeostasis. Members of the Myeloid Leukemia Factor (MLF) family have been implicated in hematopoiesis and in oncogenic blood cell transformation, but their function and molecular mechanism of action remain elusive. Previous work in Drosophila showed that MLF stabilizes the RUNX transcription factor Lozenge (LZ) and controls the number of LZ+ blood cells. During my PhD, I sought to further decipher the molecular mechanism of action of MLF on Lozenge during blood cell development. Using a proteomic approach in Drosophila Kc167 cells, we identified the Hsp40 co-chaperone family member DnaJ-1 and its chaperone partner Hsc70-4 as two partners of MLF. These interactions were confirmed by co-immunoprecipitations and in vitro pull-down assays. Importantly, we found that knocking down DnaJ-1 or Hsc70-4 expression in Kc167 cells caused a reduction in the level of Lozenge protein and a concomitant decrease in Lozenge transactivation activity, which were very similar to those caused by MLF knock-down. Similarly, over-expression of two DnaJ-1 mutants that are unable to stimulate the chaperone activity of Hsc70-4 also decreased Lozenge level and impaired its capacity to activate transcription. These results suggest that MLF could act within a chaperone complex composed of DnaJ-1 and Hsc70-4 to control Lozenge stability and activity. Along that line, we showed by co-immunoprecipitation that Lozenge interacts with MLF, DnaJ-1 and Hsc70-4, respectively. Using various truncated mutants of MLF or DnaJ-1, we showed that MLF and DnaJ-1 interact and together with Lozenge through their conserved MLF homology domain (MHD) and C-terminal region, respectively. Furthermore, in vitro GST pull-down assays suggested that the interactions between MLF, DnaJ-1 and Lozenge are direct. Thus, we propose that MLF and DnaJ-1 control Lozenge protein level by interacting with it and by promoting its folding and/or solubility via the Hsc70 chaperone machinery. In parallel, we assessed DnaJ-1 function in Drosophila blood cells in vivo using a null allele of dnaj-1 generated by CRISPR/Cas9 technique. We found that, like mlf, dnaj-1 mutation leads to an increase in the number and size of LZ+ blood cells, as well as to an over-activation of the Notch signaling pathway in these cells. Moreover, our data suggested that high levels of active Lozenge are required to control the number and size of LZ+ blood cells, and to down-regulate Notch expression. We propose that the MLF/DnaJ-1 complex controls LZ+ blood cell development in vivo by regulating Lozenge protein level/activity and thereby Notch pathway activation. In sum, our results establish a functional link between MLF, the Hsp40 co-chaperone DnaJ-1 and the RUNX transcription factor Lozenge, which could be conserved in other species.

Download or read book CtBP Family Proteins written by G. Chinnadurai and published by Springer. This book was released on 2011-01-05 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a comprehensive monograph on the CtBP family proteins. These proteins are gaining wide scientific interest due to their critical roles in animal development and in oncogenesis. The CtBP family proteins are multifunctional. They predominantly function as transcriptional corepressors in the nucleus by recruiting various histone modifying enzymes such as histone deacetylases, histone methylases and a histone demethylase. They also perform several diverse cytosolic functions such as Golgi maintenance and in central nervous system synapses.

Download or read book Hematopoiesis written by Leonard I. Zon and published by Oxford University Press. This book was released on 2001-04-12 with total page 864 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hematopoiesis, or the process of blood formation, has been extensively studied at both basic and clinical levels. Human diseases such as thalassemia, immunodeficiency, and leukemia represent defects in this process. Approaches to treat these disorders have required a basic understanding of the biology of blood cells. For instance, hemapoietic stem cell replacement or bone marrow transplantation has been used to ameliorate disease. This volume focuses on hematopoiesis at a cellular and molecular level, and establishes the basis for clinical manipulation of hematopoietic cells for therapeutic benefit. In Part I, the cellular characteristics of progenitors and stem cells are explored. Emphasis is placed on purification of stem cells and both in vitro and in vivo assays. The regulation of normal and leukemis stem cells is illustrated. An excellent discussion of potential use of these cells for gene therapy concludes this section. Hemapoiesis is easily studied during embryogenesis. Part II develops the concept of the waves of hemapoiesis during development. Comparative hematology is making a major comeback as a field in the 1990's. One hope is that general principles of hematopoiesis will be established by studying many models and systems. Part III delves into critical factors that regulate hematopoiesis, including both intracellular and extracellular signals. Part IV and V describe lineage programs for myeloid and lymphoid lineages. These chapters are meant to be illustrative of the different cell fates, but are not exhaustive. Part VI examines the genetics of hematopoisis, particularly in animal models. The hematopoietic system is in constant contact with stromal cells and endothelial cells during development and in the adult. Evidence suggests that endothelial cells and blood cells may arise from a common progenitor, the hemangioblast. Part VII and VIII discuss the stromal and endothelial cells with the emphasis on their interaction with hematopoietic cells.

Download or read book Transcriptional Control of Neural Crest Development written by Brian L. Nelms and published by Morgan & Claypool Publishers. This book was released on 2010 with total page 227 pages. Available in PDF, EPUB and Kindle. Book excerpt: The neural crest is a remarkable embryonic population of cells found only in vertebrates and has the potential to give rise to many different cell types contributing throughout the body. These derivatives range from the mesenchymal bone and cartilage comprising the facial skeleton, to neuronal derivatives of the peripheral sensory and autonomic nervous systems, to melanocytes throughout the body, and to smooth muscle of the great arteries of the heart. For these cells to correctly progress from an unspecifi ed, nonmigratory population to a wide array of dynamic, differentiated cell types-some of which retain stem cell characteristics presumably to replenish these derivatives-requires a complex network of molecular switches to control the gene programs giving these cells their defi ning structural, enzymatic, migratory, and signaling capacities. This review will bring together current knowledge of neural crest-specifi c transcription factors governing these progressions throughout the course of development. A more thorough understanding of the mechanisms of transcriptional control in differentiation will aid in strategies designed to push undifferentiated cells toward a particular lineage, and unraveling these processes will help toward reprogramming cells from a differentiated to a more naive state. Table of Contents: Introduction / AP Genes / bHLH Genes / ETS Genes / Fox Genes / Homeobox Genes / Hox Genes / Lim Genes / Pax Genes / POU Domain Genes / RAR/RXR Genes / Smad Genes / Sox Genes / Zinc Finger Genes / Other Miscellaneous Genes / References / Author Biographies

Download or read book The Secret Lives of Transcription Factors written by Willis X. Li and published by Springer Nature. This book was released on 2023-04-25 with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt: This SpringerBrief explores unconventional functions of eight different transcription factors and concludes with a discussion of their biological significance and impact, including effects on processes within the cell nucleaus during development and in adult organisms. Chapter One details unconventional functions of the transcription factors GAGA, HP1, Rb, STAT, ATF-2 and NF-kB. Surprisingly, all of these transcription factors can be found in association with heterochromatin as well as euchromatin, and in some cases unconventional functions have been demonstrated for these heterochromatin-associated factors. Chapter Two focuses on the unconventional functions of STAT and HP1 and discusses their roles in the promotion of longevity, and in protection from cancer and DNA damage. Chapter Three explores the biological significance of the findings presented in the first two chapters and considers how global changes in the epigenome brought about by factors such as STAT and HP1 might affect processes within the cell nucleus during development and in adult organisms. This succinct yet thorough SpringerBrief is essential for researchers studying epigenetics, and to instructors of the subject. It should also appeal to people interested in the control of gene transcription and other processes in the cell nucleus, and to those interested in development.

Download or read book Transcriptional Regulation of Hematopoietic Differentiation written by Nikki Ruoxi Kong and published by . This book was released on 2014 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene expression is critical for the development, patterning, and homeostasis of the organism. Precise temporal and spatial regulation of gene expression at the level of transcription requires a large network of sequence-specific factors, general transcription factors, co-factors, and epigenetic regulators. Malignancies of specific tissues often arise from perturbation of various gene expression levels. Hematopoiesis is one of the most sensitive biological processes to mis-regulation of transcription. To generate all blood cell types from embryonic development throughout the lifetime of the organism, hematopoiesis requires an intricate balance between the maintenance of a permanent stem cell pool and differentiation of multi-potent stem cells into cell types with unique functions. To generate a terminally differentiated, functional immune cell, multiple lineage-restricting steps are involved, with each governed by a specific transcription program. Therefore, gene expression regulation in hematopoietic differentiation is particularly important for an organism to properly develop, maintain oxygen transport to all tissues, and fight against infections. Furthermore, because of detailed understanding of how to isolate cells at different stages and lineages of hematopoietic differentiation, it provides an important model to study the development and differentiation of other adult tissues. Hematopoietic stem cells can be driven to differentiate along three main lineages: myeloid, erythroid, and lymphoid. Despite the discoveries of several transcription factors for specific lineages of hematopoietic differentiation, understanding the gene expression program that allow stem cells to make the decision to initiate lymphoid development still remains incomplete. For example, how is the preinititation complex of transcription (PIC) recruited to the gene promoters? Additionally, how are interactions, if any, coordinated among various sequence-specific factors that were identified via gene-by-gene knockout (KO) approaches? To form the PIC at any gene promoter, transcription factor (TF) IIA, B, D, E, F, and H, and RNA polymerase II (Pol II) must coordinate their promoter-binding and enzymatic activities. TFIID, especially, is important for promoter recognition. As a multi-subunit complex containing TATA-box binding protein (TBP) and 13-14 TBP-associated factors (TAFs), TFIID binds to sequences in the proximal promoter and allows the recruitment of other TFs and Pol II. Previously thought to be invariant from one cell type to another, recently tissue-specific roles for certain TAFs have been uncovered. TAF4B is one of the first TAFs found to have cell-specific expression, since it was identified in human B cells {Dikstein:1996wk}, though a role for its function in hematopoiesis has remained elusive. I used a Taf4b KO mouse line to study its function in both myeloid and lymphoid differentiation. I found that Taf4b KO mice were able to generate myeloid and lymphoid progenitors as well as their wild-type (WT) littermates. Furthermore, both of these types of progenitors from Taf4b KO mice can terminally differentiate into mature cells as well as those from WT mice. Finally, TAF4B-null cells are as competent as heterozygous cells (equivalent to WT in terms of Taf4b expression) to reconstitute the hematopoietic compartment of lethally irradiated mice in all cell lineages tested. In conclusion, TAF4B is dispensable in both myeloid and B cell differentiation. This could be due to TAF4B's high sequence homology with TAF4A. Alternatively, TAF4B can play a role in fine-tuning expression levels of certain B cell or myeloid-specific genes, together with another transcription factor, which cannot be uncovered in a KO mouse approach. I have made a TAF4B-specific polyclonal antibody that can be used to identify its transcriptional targets, as well as identify any potential interaction partners. Though the basal machinery does not seem to play a role in hematopoietic lineage determination, sequence-specific factors have long been implicated in this process. A study using an inducible hematopoietic-specific KO mouse line found that myocyte enhancer factor 2c (MEF2C) is necessary for multi-potent progenitors to differentiate into the lymphoid lineage {StehlingSun:2009df}. Through a candidate approach, I have identified early B cell factor 1 (EBF1) to be a specific interacting partner of MEF2C. Together, they co-occupy and functionally co-activate many B cell specific genes. When MEF2C is depleted in mice, the animals had reduced B cell gene expression as well as increased myeloid gene expression, consistent with MEF2C's role as a lineage fate regulator. I have identified and confirmed several B cell-specific genes that are co-regulated by EBF1 and MEF2C through a genome-wide survey of their binding via chromatin immunoprecipitation followed by exonuclease treatment and deep-sequencing (ChIP-exo). Furthermore, I found that p38 MAPK is the pathway through which MEF2C is phosphorylated and activated to drive B cell differentiation. When phosphorylated, MEF2C prefers to bind its co-activator EBF1, and not its co-repressor HDAC7. Taken together, the results presented in this thesis elucidated the mechanism of activation, binding partners, and downstream targets by which MEF2C is able to regulate lymphoid-specific differentiation. This study contributes to understanding how transcriptional regulation of genes can drive progenitor cells to differentiate down a particular lineage, and provide a novel mechanism for a transcription repressor to switch to an activator during cellular differentiation.

Download or read book Hematopoietic Stem Cell Development written by Isabelle Godin and published by Springer Science & Business Media. This book was released on 2010-05-27 with total page 188 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book collects articles on the biology of hematopoietic stem cells during embryonic development, reporting on fly, fish, avian and mammalian models. The text invites a comparative overview of hematopoietic stem cell generation in the different classes, emphasizing conserved trends in development. The book reviews current knowledge on human hematopoietic development and discusses recent breakthroughs of relevance to both researchers and clinicians.

Download or read book Molecular Biology of The Cell written by Bruce Alberts 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 Hematopoiesis written by and published by Academic Press. This book was released on 2016-04-29 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hematopoiesis, the latest volume in the Current Topics in Developmental Biology, covers hematopoiesis, with contributions from an international board of authors. Its chapters provide a comprehensive set of reviews covering such topics as the regulation of blood stem cell development, epigenetic mechanisms controlling erythropoiesis, and regulatory RNAs/HSCs. Covers the area of hematopoiesis International board of authors Provides a comprehensive set of reviews covering such topics as regulation of blood stem cell development, epigenetic mechanisms controlling erythropoiesis, and regulatory RNAs/HSCs

Download or read book Stem Cell Biology written by Daniel R. Marshak and published by CSHL Press. This book was released on 2001 with total page 566 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stem cells are the focus of intense interest from a growing, multidisciplinary community of investigators with new tools for isolating and characterizing these elusive cell types. This volume, which features contributions from many of the world's leading laboratories, provides a uniquely broad and authoritative basis for understanding the biology of stem cells and the current excitement about their potential for clinical exploitation. It is an essential work of reference for investigators in embryology, hematology, and neurobiology, and their potential for clinical exploitation. It is an essential work of reference for investigators in embryology, hematology, and neurobiology, and their collaborators in the emerging field of regenerative medicine.

Download or read book The influence of hyproxia an GATA 1 and Epo expression levels in developing zebrafish written by Markus Holotta and published by diplom.de. This book was released on 2014-04-11 with total page 50 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inhaltsangabe:Abstract: The transcription factor GATA-1 is essential for the development of the erythroid cell lineage in vertebrates. In this article we introduce a method to easily determine the approximately development status of red blood cells and the progression of blood formation by intensity of fluorescence in GATA-1/Ds-Red marked zebrafish. We classified the blood cells on the basis of their fluorescence intensity in 5 intensity stages (IS) with the brightest in IS 1. The comparison with our erythropoietin (Epo) data showed a noticeable correlation between GATA-1, Epo mRNA and EPO protein level. Between 2 and 3 dpf we observed a major increase in blood cell concentration to circa 1200 cells*nl-1, until 15 dpf this value decreased to about the half. The appearance of IS 1 cells correspond approximately to the peaks in Epo cRNA copies and the highest values in EPO protein emerged about 1 day later. Our data show that the blood cell concentration, Epo and Gata-1 expression in zebrafish larvae is subjected to large fluctuations in the first few days of development. The zebrafish Danio rerio, also known as Brachidanio rerio, Cyprinus rerio and others, is a omnivorous, tropical fish of the family Cyprinidae and was at fist described by Hamilton in 1822. Its natural range within Asia are slow moving or stagnant water bodies in India, Bangladesh, Nepal and Pakistan. In the past few decades the zebrafish became an important model organism for genetical, developmental and physiological studies. Fish are vertebrates and thus the genetic program is more similar to that of mammals than invertebrate models like the fruity (Drosophila melanogaster). Because of this relationship most of the zebrafish genes have human orthologs. Due to its short generation time of approximately 3 month, the rapid development and the transparency up to adulthood this tropical teleost is predestined for in vivo hematologic studies and digital imaging techniques. Especially digital imaging is a gentle, non-invasive and thereby seminal method for researcher who are working with transparent animals. The combination with fluorescent reporter genes allows real time imaging of gene expression and cell migration studies over their whole lifespan. Inhaltsverzeichnis:Table of Contents: Abbreviations4 Abstract5 1.Introduction6 1.1Zebra_sh hematopoiesis7 1.2GATA-1 and Co-factors8 1.2.1The role of GATA-18 1.2.2GATA-1 related factors10 1.3Epo and EpoR11 1.4Oxygen [...]

Download or read book Red Cell Development written by James Bieker and published by Academic Press. This book was released on 2008-02-29 with total page 291 pages. Available in PDF, EPUB and Kindle. Book excerpt: This compendium provides a concise and up-to-date assessment of critical recent issues related to erythroid biology. Developmental, epigenetic, methodological, biochemical, and clinical aspects are integrated to provide a powerful overview of their interrelationships and importance to the generation of the red cell. The excitement generated by these novel observations and the anticipation of future directions in studies of the red cell is a highlight of this volume. *The first comprehensive volume covering the breadth of the topic *The latest advancements that lead to novel directions in the study of red cells *An informative discussion of red cells as they relate to the essential oxygen-carrying component of the body

Download or read book Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis written by Laura Melinda Pillay and published by . This book was released on 2014 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt: Improper regulation of hematopoiesis generates a spectrum of defects that range from anemia and embryonic lethality to leukemia. Identifying the molecular pathways that regulate hematopoiesis is therefore a major goal of both basic and clinical biology. Vertebrate hematopoiesis occurs in two embryonic waves. The first wave, primitive hematopoiesis, influences the morphology of the developing embryonic circulatory system and produces circulating erythrocytes that facilitate tissue oxygenation during periods of rapid embryonic growth. The second, definitive wave of hematopoiesis produces multipotent hematopoietic stem cells (HSCs) that are able to differentiate into all mature blood cell lineages, self-renew, and maintain adult hematopoiesis for life. A major challenge in developmental hematopoiesis is to determine the molecular cues that regulate each phase of hematopoiesis. Previous analyses using vertebrate models have identified molecular pathways that govern both primitive and definitive hematopoiesis. These pathways are conserved among vertebrates, and the critical mammalian hematopoietic genes have clear orthologues in zebrafish. Using zebrafish as a model organism, we have identified essential regulators of both primitive and definitive hematopoiesis. We have defined a critical role for the homeodomain transcription factors Meis1 and Pbx in regulating primitive erythropoiesis. Inhibiting zebrafish Meis1 and Pbx protein synthesis cripples the production of circulating erythrocytes, and generates defects in erythropoietic gene expression. Our data place Meis1 and Pbx upstream of gata1 in the erythropoietic transcription factor hierarchy. We have also elucidated a novel role for retinoic acid (RA) signaling in definitive hematopoiesis, as RA-depleted embryos fail to produce HSCs. Previous studies have implicated RA as a critical regulator of murine Notch1 signaling, and suggest that endothelial cells require RA in order to adopt a hemogenic fate. However, our research suggests that RA is required for HSC formation prior to the formation of dorsal aorta hemogenic endothelium and that, unlike in mice, zebrafish RA does not regulate HSC formation through the Notch1-signaling pathway. Previous research by our lab has implicated the homeodomain transcription factor Hmx4 as a critical regulator of zebrafish forebrain and ocular development, and has shown that Hmx4 modulates RA signaling. However, prior to this work, the contribution of Hmx4 to embryonic hematopoiesis was unknown. We have identified putative RA-independent and dependent roles for Hmx4 in regulating primitive and definitive hematopoiesis, respectively.

Download or read book Eukaryotic Transcription Factors written by David S. Latchman and published by Academic Press. This book was released on 2010-07-28 with total page 507 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transcription, or the process by which DNA produces RNA, is a central aspect of gene expression. Transcription factors regulate transcription during development and in disease states. As such, it is critical for researchers to gain a good understanding of the relationship between the structure of various families of transcription factors and their function, as well as roles in human disease. Since publication of the Fourth Edition, there have been major advances, notably in the areas of chromatin remodeling and genome-scale analyses. This complete update includes all new coverage of the latest developments, from enabling genomic technologies to studies on the importance of post-translational modifications beyond phosphorylation events. Potential of transcription factors as therapeutic targets in human disease Importance of histone modifications Use of genome-based sequence analysis and high-throughput methods Applications of the chromatin immunoprecipitation (ChIP) assay Transcriptional elongation Regulation by post-translational modifications Regulatory networks and bioinformatics