Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development

1. Front Matter

   Pages i-xiii

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2. The Epigenetic Regulatory Machinery

   • Constanze Bonifer, Peter N. Cockerill

   Pages 1-11

3. Nonmammalian Hematopoiesis

   1. Front Matter

      Pages 13-13

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   2. What Can We Learn from Flies: Epigenetic Mechanisms Regulating Blood Cell Development in Drosophila

      • Paul Badenhorst

      Pages 15-47

   3. Epigenetic and Transcriptional Mechanisms Regulating Blood Cell Development in Zebrafish

      • Xiaoying Bai

      Pages 49-63

4. Epigenetic Mechanisms Regulating Mammalian Hematopoietic Stem Cell Development and Function

   1. Front Matter

      Pages 65-65

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   2. Epigenetic and Transcriptional Mechanisms Regulating the Development of the Haematopoietic System in Mammals

      • Maud Fleury, Flor M. Perez-Campo, Guilherme Costa, Georges Lacaud, Valerie Kouskoff

      Pages 67-93

   3. Polycomb Complexes: Chromatin Regulators Required for Cell Diversity and Tissue Homeostasis

      • Miguel Vidal

      Pages 95-139

   4. The Role of Polycomb Group Proteins in Hematopoietic Stem Cell (HSC) Self-Renewal and Leukemogenesis

      • Vincent van den Boom, Hein Schepers, Annet Z. Brouwers-Vos, Jan Jacob Schuringa

      Pages 141-173

   5. Role of the Trithorax (MLL): HOX Axis in HSC Development, Function, and Leukemia

      • Robert K. Slany

      Pages 175-204

   6. Role of DNA Methyltransferases and DNA Methylation in Cell Fate Decisions During Blood Cell Development and Leukemia

      • Grant A. Challen, Jennifer J. Trowbridge

      Pages 205-219

5. Epigenetic and Transcriptional Mechanisms Regulating Cell Fate Decisions and Blood Cell Lineage Development

   1. Front Matter

      Pages 221-221

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   2. Transcriptional and Epigenetic Regulation in the Development of Myeloid Cells: Normal and Diseased Myelopoiesis

      • Peter Laslo, Tomas Stopka

      Pages 223-245

   3. The Molecular Basis of Normal Erythroid/Megakaryocyte Development and Mechanisms of Epigenetic/Transcriptional Deregulation Leading to Erythroleukemia and Thalassaemia

      • Douglas Vernimmen

      Pages 247-266

   4. The Molecular Basis of T Cell Development and How Epigenetic/Transcriptional Deregulation Leads to T-ALL

      • Will Bailis, Warren S. Pear

      Pages 267-293

   5. Epigenetic Control of T-Cell Receptor Locus Rearrangements in Normal and Aberrant Conditions

      • Beatriz del Blanco, Úrsula Angulo, Cristina Hernández-Munain

      Pages 295-329

   6. The Molecular Basis of B Cell Development and the Role of Deregulated Transcription and Epigenetics in Leukaemia and Lymphoma

      • Christopher M. Kirkham, James N. Scott, Joan Boyes, Sarah Bevington

      Pages 331-363

6. Epigenetic Control of Immune Cell Function

   1. Front Matter

      Pages 365-365

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   2. Epigenetic Control of Immune T Cell Memory

      • Atsushi Onodera, Damon J. Tumes, Toshinori Nakayama

      Pages 367-382

   3. The Macrophage Epigenome and the Control of Inflammatory Gene Expression

      • Sara Polletti, Alessia Curina, Gioacchino Natoli, Serena Ghisletti

      Pages 383-398

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.

• blood cell lineage development
• epigenetic regulatory machinery
• hematopoietic stem cells
• immune deficiencies
• non-mammalian hematopoiesis
• transcriptional mechanisms

• Institute of Biomedical Research, University of Birmingham Medical and Dental Sciences, Birmingham, United Kingdom

  Constanze Bonifer, Peter N. Cockerill

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