Contents

Cover

Related Titles

Title Page

Preface

Chapter 1: Eukaryotic Gene Expression by RNA Polymerase II

1.1 Introduction
1.2 Transcriptional Initiation of RNA Polymerase II Genes
1.3 Transcriptional Elongation of RNA Polymerase II Genes
1.4 Transcriptional Termination of RNA Polymerase II Gene
1.5 Capping of mRNA at the 5′-End
1.6 Processing of mRNA at the 3′-End
1.7 Splicing of mRNA
1.8 Nuclear Export of mRNA for Translation
1.9 Conclusion
References

Chapter 2: Epigenetic Code: Histone Modification, Gene Regulation, and Chromatin Dynamics

2.1 Introduction
2.2 Histone Modifications
2.3 Histone Lysine Demethylation
2.4 Histone Arginine Methylation
2.5 Histone Phosphorylation and Dephosphorylation
2.6 Histone ADP-Ribosylation
2.7 Histone Ubiquitination
2.8 “Epigenetic Code” Hypothesis and Conclusion
Acknowledgments
List of Abbreviations
References

Chapter 3: Histone Lysine Methylation, Demethylation, and Hormonal Gene Regulation

3.1 Introduction
3.2 The Enzymes That Catalyze Histone Lysine Methylation and Demethylation
3.3 Histone Lysine Methylation in Hormone Signaling
3.4 Perspectives
Acknowledgments
Abbreviations
References

Chapter 4: The Role of HATs and HDACs in Cell Physiology and Disease

4.1 Introduction
4.2 HATs and HDACs
4.3 Acetylation/Deacetylation in Chromatin-Associated Functions
4.4 HATs and HDACs in Cell Physiology
4.5 Associated Diseases
References

Chapter 5: The Short and Medium Stories of Noncoding RNAs: microRNA and siRNA

5.1 Introduction
5.2 MicroRNA
5.3 Small Interfering RNA (siRNA)
5.4 Piwi interacting RNA
5.5 Transcription Initiating RNAs (TiRNAs)
5.6 Small Nuclear RNAs (snRNAs)
5.7 Conclusion
Acknowledgments
Abbreviations
References

Chapter 6: Long Noncoding RNA (lncRNA): Functions in Health and Disease

6.1 Introduction
6.2 Classification of lncRNAs
6.3 LncRNA: Functions and Mechanisms of Action
6.4 LncRNAs in Cancer
6.5 LncRNAs in Reproduction
6.6 LncRNAs in Myogenesis
6.7 LncRNA in Cardiovascular Disease
6.8 LncRNAs in Embryonic Development and Segmentation
6.9 LncRNA in Central Nervous System
6.10 LncRNAs in Neurological Disorders
6.11 LncRNA in Immune System and Immunological Disorders
6.12 Roles of lncRNAs in Various Heritable Syndromes
6.13 Conclusion
Acknowledgments
Abbreviations
References

Chapter 7: Histone Variants: Structure, Function, and Implication in Diseases

7.1 Histone Variants: Structure
7.2 Implication in Diseases
Acknowledgments
References

Chapter 8: Genomic Imprinting in Mammals: Origin and Complexity of an Epigenetically Regulated Phenomenon

8.1 Introduction: First Evidences and Extent of Genomic Imprinting
8.2 Imprinted Genes: Common Features and Diversity of Regulatory Mechanisms
8.3 Role of Imprinted Noncoding RNAs on Imprinting Control and Other Functions
8.4 Parent-of-Origin-Dependent Epigenetic Marks and the Role of Chromatin Modifications and Interactions in Imprinting
8.5 Imprinted Genes: Functions and Associated Diseases
8.6 Origin and Evolution of Imprinting
8.7 Summary and Conclusion
Acknowledgments
References

Chapter 9: Centromere and Kinetochore: Essential Components for Chromosome Segregation

9.1 Introduction
9.2 Centromeres
9.3 Kinetochores
9.4 Neocentromere
9.5 Conclusions
Acknowledgment
References

Chapter 10: Nuclear Receptors and NR-coregulators: Mechanism of Action and Cell Signaling

10.1 Introduction
10.2 Structures of Nuclear Receptors
10.3 Mode of Action of Nuclear Receptors
10.4 Nuclear Receptor Coregulators
10.5 NRs and NR-Coregulators in Human Diseases
10.6 NRs and NR-Coregulators as Drug Targets
10.7 Conclusion
Acknowledgments
Abbreviations
References

Chapter 11: Estrogen and Progesterone Receptor Signaling and Action

11.1 Introduction
11.2 Nuclear Hormone Receptor Superfamily
11.3 Estrogen and Progesterone Receptor Isoforms
11.4 Mechanisms of Estrogen and Progesterone Signaling
11.5 Integration of Membrane and Nuclear Signaling
11.6 Coregulators of Estrogen and Progesterone Signaling
11.7 Convergence of ER and PR Signaling Mechanisms: Focus on the Brain
11.8 Conclusion
References

Chapter 12: Gonadal Steroid Hormones and Brain Protection

12.1 Introduction
12.2 The Protective Effects of Estrogens on the Brain
12.3 The Protective Effects of Progesterone on the Brain
12.4 The Protective Effects of Androgens in the Brain
12.5 Clinical Studies of Estrogens in Alzheimer's Disease
12.6 Clinical Studies Addressing the Protective Effects of Progesterone and Related Progestins
12.7 Clinical Studies Addressing the Potential Beneficial Effects of Androgens
12.8 Conclusions
References

Chapter 13: Glucocorticoid Receptor-Mediated Signaling and Stress Metabolism

13.1 Introduction
13.2 Gene Regulation
13.3 Metabolism
13.4 The HPA Axis
13.5 Conclusion
References

Chapter 14: Targeting Androgen Signaling in Prostate Cancer

14.1 Introduction
14.2 Disease States of Metastatic Prostate Cancer
14.3 Androgens and Androgen Receptor
14.4 Castrate-Sensitive Prostate Cancer
14.5 Prostate Cancer Progression
14.6 Prostate Cancer Drugs
14.7 Future of Prostate Cancer Therapy
14.8 Conclusion
References

Chapter 15: Role of Peroxisome Proliferator-Activated Receptors in Inflammation and Angiogenesis

15.1 Introduction
15.2 PPARα (NR1C1)
15.3 PPARβ/δ (NR1C2)
15.4 PPARγ (NR1C3)
15.5 Concluding Remarks
References

Chapter 16: RAR/RXR-Mediated Signaling

16.1 Introduction
16.2 Vitamin A Receptors and Their Response Elements
16.3 Transcriptional RAR/RXR Signaling: The Standard Model and Recent Discoveries
16.4 Regulation of RAR Signaling: Ligand Synthesis and Metabolism
16.5 Regulation of RAR Signaling: The Role of Binding Proteins
16.6 Regulation of RAR Signaling: Receptor Expression, Modification, and Degradation
16.7 Transrepression and Crosstalk with Other Transcription Factors
16.8 Nongenomic Mechanisms of RA/RAR Signaling
16.9 The Role of Retinoid Binding Proteins in Phototransduction
16.10 Retinoic acid-Regulated Genes
16.11 Conclusion
List of Abbreviations and Symbols
References

Chapter 17: On the Trail of Thyroid Hormone Receptor Epigenetics

17.1 Introduction
17.2 Overview of Thyroid Hormone Action
17.3 Molecular Mechanisms of Regulation of Gene Expression by Thyroid Hormone-Specific Nuclear Receptors
17.4 Nongenomic Mechanism of Action of Thyroid Hormones
17.5 Conclusion
References

Chapter 18: Insulin Signaling, Epigenetics, and Human Diseases

18.1 Introduction to Epigenetics
18.2 Types of Epigenetic Modifications
18.3 Epigenetic Links to Endocrine System
18.4 Insulin
18.5 Insulin Signaling
18.6 Insulin Receptor
18.7 Insulin Receptor Substrate (IRS)
18.8 The PI(3)K Pathway
18.9 The Ras Pathway
18.10 Insulin Resistance and Metabolic Derangements
18.11 Conclusion
Acknowledgment
Abbreviations
Function of the Genes Discussed in this Chapter
References

Chapter 19: Endocrine Disruptors and Epigenetics

19.1 Introduction
19.2 Endocrine Disruptors
19.3 Associated Diseases
19.4 Endocrine Disruptors and Development of Transgenerational Disease
19.5 Discussion
References

Chapter 20: Endocrine Disruptors: Mechanism of Action and Impacts on Health and Environment

20.1 Introduction
20.2 Mechanism of Action of EDC
20.3 Bisphenol A (BPA) and its Health Impacts
20.4 Diethylstilbestrol (DES)
20.5 Atrazine
20.6 Polychlorinated Biphenyls (PCBs)
20.7 Phthalates
20.8 Phytoestrogens
20.9 Methoxychlor
20.10 Dioxins: An Environmental Contaminant
20.11 Conclusion
Acknowledgments
Abbreviations
References

Index

End User License Agreement

List of Illustrations

Figure 1.1

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 3.1

Figure 3.2

Figure 4.1

Figure 4.2

Figure 4.3

Figure 4.4

Figure 5.1

Figure 5.2

Figure 5.3

Figure 5.4

Figure 6.1

Figure 6.2

Figure 6.3

Figure 6.4

Figure 6.5

Figure 6.6

Figure 6.7

Figure 6.8

Figure 7.1

Figure 7.2

Figure 7.3

Figure 7.4

Figure 8.1

Figure 8.2

Figure 8.3

Figure 9.1

Figure 9.2

Figure 10.1

Figure 10.2

Figure 10.3

Figure 10.4

Figure 10.5

Figure 10.6

Figure 10.7

Figure 11.1

Figure 11.2

Figure 11.3

Figure 11.4

Figure 11.5

Figure 12.1

Figure 13.1

Figure 13.2

Figure 13.3

Figure 13.4

Figure 13.5

Figure 13.6

Figure 13.7

Figure 13.8

Figure 14.1

Figure 14.2

Figure 14.3

Figure 14.4

Figure 14.5

Figure 15.1

Figure 15.2

Figure 15.3

Figure 16.1

Figure 16.2

Figure 16.3

Figure 16.4

Figure 16.5

Figure 16.6

Figure 16.7

Figure 17.1

Figure 17.2

Figure 17.3

Figure 17.4

Figure 17.5

Figure 18.1

Figure 18.2

Figure 18.3

Figure 19.1

Figure 19.2

Figure 19.3

Figure 19.4

Figure 19.5

Figure 19.6

Figure 19.7

Figure 19.8

Figure 20.1

Figure 20.2

Figure 20.3

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Preface

First of all, I am pleased that the book Gene Regulation, Epigenetics and Hormone Signaling has reached to the hands of the readers. I thank all the contributors and Wiley editors for their contributions and patience. In this book I have tried to include different aspects of eukaryotic gene regulation with an emphasis on epigenetics and hormone signaling. Histone modifications, DNA methylation, and noncoding RNAs are emerging as master players in gene regulation and their malfunction is closely associated with severe human diseases. The first nine chapters of the book emphasize on fundamentals of eukaryotic transcription, the mechanisms of gene activation and silencing, histone modifications, histone variants, noncoding RNA, DNA methylation, and centromere structure–function relationship. Importantly, gene expression and chromatin dynamics are highly influenced by a variety of factors such as hormones and nutrients, and may also be affected by a variety of environmental contaminants that contribute to human disease. These stimuli induce epigenetic changes/modifications that ultimately dictate the fate of chromosome and gene activation and silencing. In the rest of the book (11 chapters), we have emphasized on the mechanisms of hormone signaling and endocrine disruption. There are many different types of hormones, including steroid hormones, peptide-based hormones, and amino acid-derived hormones. Considering the limitations in length of the books, I could not include all different hormone-signaling pathways. However, we have included cell signaling mechanisms associated with estrogen, androgen, glucocorticoid, thyroid hormone, PPAR signaling, and retinoic acid signaling. Among the peptide hormones, the insulin signaling is included in this book. The last two chapters in the book is capped with epigenetic and health impacts of variety of endocrine disrupting chemicals. In addition to fundamental of cell signaling, most chapters highlight the potential drug targets, diagnosis markers, and potential therapy associated with human disease. We have assembled contributions from different experts in the field. In Chapter 2, I have also introduced the concept of “epigenetic code hypothesis” that states that there are epigenetic factors including histone modification, DNA modification, histone variants, and wide ranges of noncoding RNA, coordinate in a concerted fashion, and orchestrate the chromatin dynamics and gene expression decision and this adds additional layers of regulation on gene expression beyond just “genetic code.” Alteration or interference in the epigenetic programming results in abnormal gene expression causing severe human diseases. Overall, this book provides fundamental to advanced levels of understanding on human gene regulation, epigenetics, and cell signaling, with emphasis on human health and disease. Finally, I would like to thank Mandal lab family (my past and present students, postdoctorates, and research scholars) whose research and discoveries inspire me daily and encourage to peruse the book. I also thank my sweet family (especially my wife Saoni) for their endless support, love, and patience throughout.