Chromatin Readers in Health and Disease

1st Edition - September 22, 2023

Editors: Olivier Binda, Trygve O Tollefsbol

Paperback ISBN:

9 7 8 - 0 - 1 2 - 8 2 3 3 7 6 - 4

eBook ISBN:

9 7 8 - 0 - 3 2 3 - 9 0 3 1 4 - 1

Chromatin Readers in Health and Disease, Volume 35, a new release in the Translational Epigenetics series, gathers and makes actionable our current understanding of how chromatin… Read more

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Chromatin Readers in Health and Disease, Volume 35, a new release in the Translational Epigenetics series, gathers and makes actionable our current understanding of how chromatin readers regulate access to genetic information, and how their aberrant regulation can contribute to human pathologies. Chromatin readers discussed include 14-3-3 Dinshaw, ADD, Ankyrin, BAH, BET, BIR, BRCT, bromodomains and Kac readers, chromodomains and chromobarrel readers, citrullination readers, macrodomains and poly-ADP-ribose readers, MBT, PHD and double PHD, PWWP, SUMO (H4K12) readers, Tudor and TTD, UDR and ubiquitin, WD40, YEATS (crotonyl reader), MBD, SRA, and Methyl-RNA readers.In the book, more than a dozen leaders in the field examine a range of protein readers, their relationship to human disease, and the early therapeutics that act as chromatin signaling factors to treat cancers and Huntington's disease, among other disorders.

Cover image
Title page
Table of Contents
Front Matter
Copyright
Contributors
Preface
Summary
Chromatin
Histone modifiers
Histone mark readers
Trending methods
References
Section 1: Histone mark readers
Chapter 1: ADD domains—A regulatory hub in chromatin biology and disease
Abstract
Acknowledgments
Structure of the ATRX-ADD domain
Histone tail interaction and structures of DNMT3-ADD domains
Histone tail interaction of the ATRX-ADD domain
Allosteric regulation of DNMT3A activity by the ADD domain
Protein-protein interaction of ADD domains
Disease connections of ADD domains
Conclusions
References
Chapter 2: The BAH domain: A versatile histone modification reader
Abstract
Identification of the BAH domain as a modification-sensitive histone H4 amino terminus reader
Structural insights
Structures of the free Sir3 BAH domain
Structures of the Sir3-BAH and Orc1-BAH bound to the nucleosome
Nucleosome and histone H3 binding by the Rsc2 BAH domain
Recognition of methylated histone H3 and H4 tails
Nonhistone protein-protein interactions
Concluding remarks
References
Chapter 3: BRCT domains as chromatin readers: Structure, function, and clinical implications
Abstract
Acknowledgments
Discovery of BRCT domains as regulators of p53 function and phospho-dependent binders of chromatin-associated DNA repair proteins
BRCT domain involvement in chromatin signaling after DNA damage and in specific types of DNA repair
Mutations in BRCT domain-containing proteins cause human disease
References
Chapter 4: The bromodomain acyl-lysine readers in human health and disease
Abstract
Acknowledgments
Lysine acylation and the bromodomain
Metabolism and its links to acyl-lysine biology
The structure and biological functions of the bromodomain
Pharmacological targeting of bromodomains
Bromodomains and human diseases
Conclusions
References
Chapter 5: CHROMO domain readers: A rainbow of opportunities
Abstract
Introduction
Structural insights of chromodomains and their interactions with methylated histone residues
Classification and functions of the chromodomain-containing protein family
CD-containing proteins and human disease
Current advances in targeting CD-containing proteins
Conclusions and perspectives
References
Chapter 6: The MBT proteins: Methyl-lysine readers for stem cells, development, and tumors
Abstract
Acknowledgments
Introduction
Structure of the MBT repeated domain
Conclusion
References
Chapter 7: Epigenetically decipherING the genome: A role for PHDs
Abstract
Regulation of gene expression defines cell type and function
PHD finger proteins regulate gene expression
Forms of readers of the histone code
Structural bases for PTM recognition by PHD finger proteins
Major physiological and biochemical pathways regulated by PHD finger proteins
References
Chapter 8: Recognition of histone methylation and DNA by the PWWP domain: Mechanism and function
Abstract
Introduction
Biochemical and structural studies of PWWP domains
Functional roles of PWWP domains in biology and disease
Conclusion
References
Chapter 9: Spin repeats and human pathologies
Abstract
Acknowledgment
Introduction
Molecular functions of Spin repeats
Functions of Spin repeat proteins in gametogenesis and early development
The multifaceted roles of SPIN1 in cancer
Role of SPIN1 in hepatitis B virus infection
Small molecules designed for SPIN1
Conclusion
References
Chapter 10: Chromatin readers of the WD-repeat containing protein family
Abstract
Acknowledgments
Conflict of Interest
Introduction
Histone chaperones
Histone-modifying and chromatin-remodeling complexes
Implications of a binary methylarginine switch
Conclusions and perspectives
References
Chapter 11: The multifunctional YEATS domain in chromatin biology
Abstract
Introduction
YEATS domains are readers of lysine acylation
YEATS domain binding preferences
Structural features of the acyl-lysine binding site
Modular organization of YEATS domain-containing proteins
Roles of YEATS domain-containing proteins in chromatin-modifying and transcription factor complexes
Genes encoding YEATS domain-containing proteins are putative oncogenes
Inhibitors that target YEATS domains
YEATS domain-containing proteins in other diseases
Emerging topics in YEATS domain biology
Conclusions
References
Section 2: Methyl-DNA and -RNA readers
Chapter 12: DNA methylation and reader or writer proteins: Differentiation and disease
Abstract
Introduction to DNA methylation
Caveats about DNA methylation’s roles in regulating gene expression and modulating recognition by DNA-binding proteins
DNA methylation: Overview of relationship to mammalian differentiation, disease, and aging
Effects of DNA methylation at promoters on transcription
Maintenance of CGI promoters in the unmethylated state: CXXC-domain DNA-binding proteins and other transcription factors
Effects on transcription of DNA methylation at enhancers
Transcription factors and DNA methylation
DNA methylation readers and writers in disease
Conclusions
References
Section 3: Recent methods in chromatin signaling
Chapter 13: CUT&RUN and CUT&Tag: Low-input methods for genome-wide mapping of chromatin proteins
Abstract
Introduction
CUT&RUN
CUT&Tag
Before you begin
Step-by-step method details
References
Index

Olivier Binda

Dr. Olivier Binda is a Principal Investigator at Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, England, specializing in epigenetics and gene expression as it relates to human disease. Dr. Binda co-edited Chromatin Signaling and Diseases (Elsevier 2016), a volume in Elsevier’s Translational Epigenetics series, and has published 20 scientific papers in such peer reviewed journals as the 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

Principal Investigator, Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

Trygve O Tollefsbol

Dr. Tollefsbol is a Distinguished Professor of Biology and a Senior Scientist in the O’Neal Comprehensive Cancer Center, Integrative Center for Aging Research, Nutrition Obesity Research Center, University Wide Microbiome Center, and the Comprehensive Diabetes Center at the University of Alabama at Birmingham (UAB). He is Director of the UAB Cell Senescence Culture Facility which he established in 1999. Dr. Tollefsbol trained as a Postdoctoral Fellow and Assistant Research Professor with members of the National Academy of Science at Duke University and the University of North Carolina. He earned doctorates in molecular biology and osteopathic medicine from the University of North Texas Health Sciences Center and his bachelor’s degree in Biology from the University of Houston. He has received prior funding from the NCI, NHLBI, NIMH and other federal institutes as well as the Glenn Foundation for Medical Research, Susan G. Komen for the Cure, the American Federation for Aging Research (AFAR), and the American Institute for Cancer Research (AICR) among many other sources.

Affiliations and expertise

Distinguished Professor of Biology, University of Alabama at Birmingham, AL, USA