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E-raamat: Chromatin Signaling and Diseases

Edited by (Associate Professor of Medicine, Associate Professor Pharmacology, Mayo Institute, Rochester, MN,), Edited by (Principal Investigator, Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK)
  • Formaat: EPUB+DRM
  • Ilmumisaeg: 06-Aug-2016
  • Kirjastus: Academic Press Inc
  • Keel: eng
  • ISBN-13: 9780128026090
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  • Formaat: EPUB+DRM
  • Ilmumisaeg: 06-Aug-2016
  • Kirjastus: Academic Press Inc
  • Keel: eng
  • ISBN-13: 9780128026090

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Chromatin Signaling and Diseases covers the molecular mechanisms that regulate gene expression, which govern everything from embryonic development, growth, and human pathologies associated with aging, such as cancer. This book helps researchers learn about or keep up with the quickly expanding field of chromatin signaling. After reading this book, clinicians will be more capable of explaining the mechanisms of gene expression regulation to their patients to reassure them about new drug developments that target chromatin signaling mechanisms. For example, several epigenetic drugs that act on chromatin signaling factors are in clinical trials or even approved for usage in cancer treatments, Alzheimers, and Huntingtons diseases. Other epigenetic drugs are in development to regulate various class of chromatin signaling factors. To keep up with this changing landscape, clinicians and doctors will need to stay familiar with genetic advances that translate to clinical practice, such as chromatin signaling.Although sequencing of the human genome was completed over a decade ago and its structure investigated for nearly half a century, molecular mechanisms that regulate gene expression remain largely misunderstood. An emerging concept called chromatin signaling proposes that small protein domains recognize chemical modifications on the genome scaffolding histone proteins, facilitating the nucleation of enzymatic complexes at specific loci that then open up or shut down the access to genetic information, thereby regulating gene expression. The addition and removal of chemical modifications on histones, as well as the proteins that specifically recognize these, is reviewed inChromatin Signaling and Diseases. Finally, the impact of gene expression defects associated with malfunctioning chromatin signaling is also explored.Explains molecular mechanisms that regulate gene expression, which governs everything from embryonic development, growth, and human pathologies associated with agingEducates clinicians and researchers about chromatin signaling, a molecular mechanism that is changing our understanding of human pathologyExplores the addition and removal of chemical modifications on histones, the proteins that specifically recognize these, and the impact of gene expression defects associated with malfunctioning chromatin signalingHelps researchers learn about the quickly expanding field of chromatin signaling

Muu info

Examining the molecular mechanisms that regulate gene expression to facilitate new drug developments through targeting chromatin signaling mechanisms, this go-to reference reviews the addition and removal of chemical modifications on histones, the proteins that specify them, and the impact of gene expression defects associated with malfunctioning chromatin signaling
List of Contributors xi
Bases of Chromatin Signaling and Their Impact on Diseases Pathogenesis xiii
I Histone Mark Writers
1 Histone Acetyltransferases, Key Writers of the Epigenetic Language
3(22)
X.J. Yang
Introduction
3(1)
Functional and Mechanistic Impact of Histone Acetylation
4(1)
Identification of the First Histone Acetyltransferases, a Historical Perspective
5(3)
Yeast Histone Acetyltransferases Belong to Three Different Families
8(3)
Three Families of Metazoan Histone Acetyltransferases and Their Roles in Animal Development
11(4)
Role of Histone Acetyltransferases in the Pathogenesis of Human Diseases
15(2)
Conclusions and Future Directions
17(1)
List of Acronyms and Abbreviations
17(1)
Glossary
18(1)
References
18(7)
2 Impacts of Histone Lysine Methylation on Chromatin
25(30)
S. Lanouette
. Haddad
P. Zhang
J.F. Couture
Chromatin Regulation and Posttranslational Modifications
26(1)
Histone Lysine Methyltransferases
27(1)
Histone H3K4 Methylation
28(3)
Histone H3K9 Methylation
31(2)
Histone H3K27 Methylation
33(2)
Histone H3K36 Methylation
35(1)
Histone H3K79 Methylation
36(2)
Histone H4K20 Methylation
38(1)
Monomethylation of H4K20 Promotes Mitotic Chromatin Condensation and DNA Replication
39(1)
Emerging Roles of Non-Canonical Histone Lysine Methylation
40(1)
Conclusions
41(1)
List of Acronyms and Abbreviations
42(1)
References
42(13)
3 The Role of Histone Mark Writers in Chromatin Signaling: Protein Arginine Methyltransferases
55(20)
N. Haghandish
J. Cote
Introduction
55(1)
General Properties of Protein Arginine Methyltransferases
56(5)
Mammalian Protein Arginine Methyltransferases and Their Effects on Gene Expression
61(9)
Conclusions
70(1)
List of Acronyms and Abbreviations
70(1)
Glossary
71(1)
Acknowledgments
71(1)
References
71(4)
4 Histone Kinases and Phosphatases
75(22)
N.A. Watson
J.M.G. Higgins
Introduction
75(1)
Histone Phosphorylation: Basic Concepts
75(3)
Histone Kinases in Nucleosome Packing and Assembly
78(1)
Histone Kinases and Cell Division
78(4)
Histone Kinases in DNA Repair and Replication
82(1)
Histone Kinases and Programmed Cell Death
83(1)
Histone Kinases and Transcription
84(3)
Histone Phosphatases
87(1)
Conclusions
88(1)
List of Acronyms and Abbreviations
88(1)
Glossary
89(1)
References
89(8)
II Histone Mark Readers
5 The Bromodomain as an Acetyl-Lysine Reader Domain
97(16)
S.G. Smith
M.M. Zhou
Lysine Acetylation and the Bromodomain
97(1)
Discovery of the Bromodomain as an Acetyl-Lysine Recognition Module
98(2)
Biological Functions of Bromodomain Proteins
100(4)
Bromodomain Proteins in Human Disease Pathways
104(1)
Small Molecular Inhibitors of Bromodomains
104(3)
Conclusion
107(1)
List of Acronyms and Abbreviations
108(1)
Acknowledgments
108(1)
References
108(5)
6 Chromo Domain Proteins
113(14)
J.C. Eissenberg
Introduction
113(1)
The Chromo Domain Structure
114(1)
Varieties of Chromo Domains
114(3)
Chromo Shadow Domain
117(1)
Nucleic Acid-Binding Chromo Domains
117(1)
Posttranslational Modifications and Chromo Domain Transactions
118(1)
Targeting Chromo Domains for Therapeutics
119(1)
Chromo Domain Association With Human Disease
120(1)
Conclusion
121(1)
List of Acronyms and Abbreviations
121(1)
Acknowledgments
122(1)
References
122(5)
7 The Role of PHD Fingers in Chromatin Signaling: Mechanisms and Functional Consequences of the Recognition of Histone and Non-Histone Targets
127(22)
E.A. Morrison
C.A. Musselman
Introduction
128(1)
The History of the Plant Homeodomain Finger
128(1)
The Structural Basis of Histone Recognition
128(4)
The Mechanism of Plant Homeodomain Fingers in the Combinatorial Readout of Patterns of Histone Post-Translational Modifications
132(5)
Non-Histone Targets
137(1)
Understanding the Role of the Plant Homeodomain Finger in the Function of Its Host Protein
138(2)
Plant Homeodomain Fingers in Disease
140(2)
Conclusion
142(1)
References
143(6)
8 Tudor Domains as Methyl-Lysine and Methyl-Arginine Readers
149(20)
M.V. Botuyan
G. Mer
Introduction
149(1)
The Aromatic Cage: Molecular Basis of Methyl-Lysine and Methyl-Arginine Recognition
150(2)
Tudor Domains Interacting With Methylated Lysine-Containing Peptides
152(6)
Tudor Domains Interacting With Methylated Arginine-Containing Peptides
158(2)
Conclusion
160(1)
Acknowledgments
161(1)
References
161(8)
III Histone Mark Erasers
9 Histone Deacetylases, the Erasers of the Code
169(10)
M.J. Lamberti
R.E. Vera
N.B. Rumie Vittar
G. Schneider
Introduction
169(1)
Histone Modifications and Gene Transcription
170(1)
Histone Deacetylase Families and Classes
171(1)
Histone Deacetylases Structures and Catalytic Mechanisms
172(1)
Histone Deacetylases as Modulators of the Epigenome
172(2)
Histone Deacetylases Biology
174(2)
Conclusion
176(1)
List of Abbreviations
176(1)
References
176(3)
10 Lysine Demethylases: Structure, Function, and Disfunction
179(18)
M.A. Garcia, R. Fueyo
M.A. Martinez-Balbas
Introduction
179(1)
Families: Functional and Structural Features
180(2)
Transcriptional Output and Regulation
182(2)
Physiological Role
184(2)
KDM-Associated Diseases
186(3)
KDM Inhibitors as New Epigenetic Drugs
189(2)
Conclusion
191(1)
Acknowledgments
191(1)
References
191(6)
IV Chromatin Signaling
11 Variation, Modification, and Reorganization of Broken Chromatin
197(20)
T.C. Humphrey
J.A. Downs
A.L. Chambers
Introduction
197(1)
Histone Modifications in DSB Repair
198(3)
Histone Variants in DSB Repair
201(4)
Chromatin Remodeling Enzymes in DSB Repair
205(6)
Conclusion
211(1)
References
211(6)
12 Crosstalk Between Histone Modifications Integrates Various Signaling Inputs to Fine-Tune Transcriptional Output
217(24)
S. Nagarajan
S.A. Johnsen
Introduction
217(1)
Crosstalk Between Histone Modifications and Their Consequences
218(1)
Histone Marks and Recruitment of Chromatin Factors
218(3)
Histone Lysine Methylation and Acetylation
221(1)
Histone Ubiquitination and Methylation: a Trans Effect
222(2)
Histone Phosphorylation
224(2)
Histone-Modifying Complexes Have Multiple Catalytic Roles and Functions
226(3)
Histone Arginine Methylation
229(1)
Histone Tail Cleavage Exhibits the Ultimate Irreversible Removal of Histone Modifications
230(1)
Histone Modification at Enhancers
231(1)
Conclusion
231(1)
List of Acronyms and Abbreviations
232(3)
Glossary
235(1)
References
235(6)
13 Signaling and Chromatin Networks in Cancer Biology
241(16)
E. Hessmann
R. Urrutia
A. Koenig
Introduction
241(1)
Regulation of Epithelial-Mesenchymal-Transition
242(1)
Chromatin Remodeling in the Regulation of Cancer Cell Plasticity
243(2)
The Epithelial-Mesenchymal-Transition Transcription Factor Machinery
245(4)
The Role of Posttranscriptional Regulation of Epithelial-Mesenchymal-Transition
249(1)
Perspective
249(1)
References
250(7)
V Chromatin Dynamics In Normal And Disease Conditions
14 Crosstalk Between DNA Methylation and Chromatin Structure
257(14)
M. Roque
L. Vargas-Roig
Introduction
257(2)
Crosstalk Between DNA Methylation and Chromatin Structure
259(5)
Significance of Altered DNA-Chromatin Crosstalk in Disease
264(3)
Conclusions
267(1)
List of Abbreviations
267(1)
References
268(3)
15 Epigenetic Regulation of Endoplasmic Reticulum Stress
271(16)
K. Barroso
E. Chevet
Introduction
271(10)
Conclusions
281(1)
Acronyms
282(1)
Acknowledgments
282(1)
References
282(5)
16 Chromatin Signaling in Aging and Cellular Senescence
287(24)
F. Couteau
F.A. Mallette
Aging, Cellular Senescence, and Chromatin: an Introduction
288(2)
Nucleosomal Modifications in Senescence and Aging
290(3)
Histone Posttranslational Modifications During Cellular Senescence and Aging
293(4)
Modulation of Lifespan by Experimental Alteration of Chromatin Modifiers in Animal Models
297(3)
Age-Dependent Regulation of the Chromatin-Metabolism Connection
300(1)
Effect of Telomere Shortening on Telomeric Chromatin
301(1)
Conclusion
302(1)
List of Acronyms and Abbreviations
303(1)
References
303(8)
17 Chromatin Dynamics and Epigenetics of Stem Cells and Stem-Like Cancer Cells
311(18)
A. Gaspar-Maia
A. Sevilla
Introduction
311(1)
Nuclear Architecture
312(1)
Chromatin Structure
312(1)
Histone Modifications and Variants
313(1)
Chromatin Remodeling
314(3)
Chromatin Dynamics During Embryo Development
317(1)
Chromatin Dynamics During Lineage Differentiation
317(1)
Cancer Stem-Like Cells: Historical Perspective
318(2)
Epigenetic Factors Regulating Tumorigenesis and Cancer Stem Cells
320(1)
Histone Modifications and Variants in CSCs
320(2)
Chromatin Remodeling in CSCs
322(2)
Conclusion
324(1)
References
324(5)
18 Altered Chromatin Signaling in Cancer
329(18)
A.S. Liss
Introduction
329(2)
Epigenetic Readers
331(1)
Polycomb and Trithorax
332(9)
Metabolic Regulation of Epigenetic Signaling
341(1)
Conclusion
342(1)
References
342(5)
19 Impact of Chromatin Changes in Pathogenesis of Infectious Diseases: A Pathogen View
347(18)
A. Ropolo
M.C. Touz
Parasites
347(8)
Yeast
355(4)
Conclusion
359(1)
References
360(5)
20 Chromatin Remodeling and Epigenetic Reprogramming in Chronic Disease and Cancer in the Liver and Pancreas
365(22)
M.G. Fernandez-Barrena
C.L. Pin
Introduction
365(1)
Development of Pancreas and Liver
366(3)
Epigenetics of Liver Diseases
369(5)
Epigenetics of Pancreatic Diseases
374(5)
Future Directions: Clinical Potential of Targeting Chromatin-Remodeling Proteins
379(1)
Acknowledgments
380(1)
References
380(7)
21 Pharmacological and Therapeutic Targeting of Epigenetic Regulators
387(16)
R. Urrutia
G.A. Lomberk
Introduction
387(1)
Targeting the DNA Methylation Pathway
388(2)
The RNA World
390(1)
Histone Acetylases and Deacetylases
391(3)
Histone Methylases and Demethylases
394(4)
Chromatin Readers
398(1)
Concluding Remarks
399(1)
References
400(3)
22 Use of Chromatin Changes as Biomarkers
403(20)
R.A. Hlady
K.D. Robertson
Introduction
403(4)
Concept 1: Altered DNA Methylation Landscapes as Biomarkers of Human Disease
407(2)
Concept 2: Aberrant microRNA Expression in Disease States
409(3)
Concept 3: Disease-Specific Histone Posttranslational Modifications Function as Biomarkers
412(1)
Concept 4: Tissue Surrogate Epigenetic Biomarkers
413(3)
Conclusion
416(1)
List of Acronyms and Abbreviations
417(1)
Glossary
418(1)
Acknowledgments
418(1)
References
418(5)
23 Regulation of Host Chromatin by Bacterial Metabolites
423(20)
S. Mani
Introduction
423(1)
The Commensal Bacterial Metabolome
424(1)
Dietary Carcinogens Alter Chromatin
424(1)
Bile Acids: Microbial Bile-Ome and Nuclear Receptors
425(1)
Estrogens: Microbial Estrabolome and Chromatin Modulation
426(1)
Ellagic Acid and Histones Methylation
426(1)
Short Chain Fatty Acids (SCFAs), G Protein-Coupled Receptors, and Histone Deacetylases
426(1)
Indoles and Nuclear Receptors
427(3)
Polyketides
430(1)
Bacterial Nucleomodulins
431(1)
Miscellaneous
431(1)
Non-Mammalian Systems
431(1)
Plants
432(1)
Lessons to Apply from Host Intermediary Metabolism and Chromatin
432(1)
Metabolite Mining for Chromatin Modulation
433(2)
Conclusion
435(1)
List of Acronyms and Abbreviations
435(1)
References
435(8)
Index 443
Dr. Olivier Binda is a Researcher at the University of Ottawa, specializing in epigenetics and gene expression as it relates to human diseases. Dr. Binda co-edited Chromatin Signaling and Diseases (Elsevier 2016), a volume in Elseviers Translational Epigenetics series, and has published 20 scientific papers in such peer reviewed journals as the Molecular Cell, Journal of Biological Chemistry, Biochemistry, Epigenetics, Oncogene, Scientific Reports, and Stem Cell Research. In past positions he has served as a postdoctoral fellow at McGill University and Stanford University, and he completed his PhD in Biochemistry at McGill University in 2007.

Affiliations and expertise

University of Ottawa, Department of Cellular and Molecular Medicine, Ottawa, CANADA.

The research program of Martin E. Fernandez-Zapico, M.D., focuses on the cellular and molecular characterization of epigenetic pathways regulating pancreatic carcinogenesis, a dismal disease with one of the poorest prognoses among all neoplasms. Specifically, Dr. Fernandez-Zapico and his team study the modulation of chromatin and nuclear dynamics by oncogenic cascades and its impact in gene expression regulation, a critical step during pancreatic neoplastic transformation.Dr. Fernandez-Zapico and his team are confident that the knowledge derived from his studies will help with the understanding of the contribution of these epigenetic events to the initiation and/or progression of pancreatic carcinogenesis as well as serve as a foundation for the development of new therapeutic approaches.Dr. Fernandez-Zapico's program is affiliated with the Mayo Clinic Cancer Center, Department of Oncology, Division of Gastroenterology and Hepatology, and the Center for Cell Signaling in Gastroenterology. His research is supported by the National Institutes of Health (NIH), the NIH-funded Mayo Clinic Pancreatic Cancer Specialized Program of Research Excellence (SPORE), the NIH-funded Mayo Clinic Center for Cell Signaling in Gastroenterology, and the Leukemia and Lymphoma Foundation.