Polycomb Group Proteins - 1st Edition - ISBN: 9780128097373, 9780128098226

Polycomb Group Proteins

1st Edition

Authors: Vincenzo Pirrotta
eBook ISBN: 9780128098226
Hardcover ISBN: 9780128097373
Imprint: Academic Press
Published Date: 5th January 2017
Page Count: 372
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Polycomb Group Proteins is a comprehensive volume detailing the mechanisms that are key to the management of genome function in many different contexts, from embryonic stem cells to terminal differentiation. The book discusses the regulation of cell lineages, cell proliferation, apoptosis, X chromosome inactivation, and most major genome programming choices.

In the last few years, the biochemical understanding of PRC1-type complexes has greatly expanded in terms of the number of components involved and the intricacies of their interactions. The functionalities of these various complexes and their components are not all well understood, but recent work has shown an important division of labor and roles in the recruitment of stable binding in the ability to lay the groundwork of histone modifications and in the epigenetic maintenance of repressed states.

In an effort to provide clarity in this topical research area, the book provides a cluster of chapters that deal with variant PRC1 complexes, their taxonomy, their components, their interactions, and what is known of their functions.

Key Features

  • Provides topical coverage on accessory components that are known to be involved in PcG recruitment in Drosophila and their less understood role in mammals
  • Includes dedicated sections on PRC1 complexes and PRC2 complexes for quick reference
  • Features the role of RNA molecules in different aspects of Polycomb proteins involvement in epigenetic regulation, beginning with the key role of the Xist RNA in recruiting and spreading PcG complexes on the inactive X chromosome


Geneticists, molecular biologists, biochemists, researchers, and clinicians studying the underlying basis of human disease and novel means to treat human diseases that are caused by reversible epigenetic processes

Table of Contents

  • Translational Epigenetics Series
  • List of Contributors
  • Editor's Biography
  • Acknowledgments
  • Chapter 1. Introduction to Polycomb Group Mechanisms
  • Chapter 2. The Role of RAWUL and SAM in Polycomb Repression Complex 1 Assembly and Function
    • Introduction
    • Polycomb Group
    • Polycomb Group RAWUL
    • Polycomb Group SAMs
    • Summary
    • List of Acronyms and Abbreviations
  • Chapter 3. The Chromodomain of Polycomb: Methylation Reader and Beyond
    • Introduction
    • Polycomb Chromodomain Specifically Recognizes H3K27me3
    • Structural Basis for the Polycomb–H3K27me3 Interaction Specificity
    • Mammalian Polycomb Homologs Bind Differentially to Methylated Histone H3
    • Cross Talk Between Histone Methylation and Other Posttranslational Modifications
    • Putative Nonhistone Targets of Polycomb Group Chromodomains
    • Noncoding RNA: Noncanonical Partners of Polycomb Group Chromodomains
    • Chemical Probes for CBX7 Chromodomain
    • Polycomb Homologs From Yeast and Plant: Evolutionarily Conserved Biological Significance of Chromodomain
    • Conclusion
    • List of Acronyms and Abbreviations
    • Glossary
  • Chapter 4. Unraveling the Roles of Canonical and Noncanonical PRC1 Complexes
    • Background
    • The Mechanism of Action of Canonical Polycomb Repressive Complexes 1
    • The Mechanism of Action of Noncanonical Polycomb Repressive Complexes 1
    • The Biological Importance of Canonical Polycomb Repressive Complex 1, Noncanonical Polycomb Repressive Complex 1, and H2A Monoubiquitination
    • Perspectives
    • List of Acronyms and Abbreviations
  • Chapter 5. Structure and Biochemistry of the Polycomb Repressive Complex 1 Ubiquitin Ligase Module
    • Introduction
    • Ubiquitin Conjugation and Deconjugation
    • PRC1 Is a RING E3 Ligase
    • The Active E3 Ligase Is a Heterodimer of BmI1 and Ring1
    • Biochemical and Structural Studies of the RING Domains of the BmI1-Ring1B Heterodimer
    • Recognition of E2 Enzymes by BmI1-Ring1B
    • Interaction of BmI1-Ring1B-UbcH5c With Substrate
    • Structure of the PRC1 Ubiquitin Ligase Module Bound to Nucleosome
    • Variant PRC1 Complexes and the Mechanism of Ubiquitin Transfer
    • Which PRC1 Contributes Most to H2A Ubiquitination?
    • Is H2A Ubiquitination Really Important?
    • What Does uH2A Do?
    • What's Next for PRC1 and uH2A?
  • Chapter 6. Cooperative Recruitment of Polycomb Complexes by Polycomb Response Elements
    • Introduction
    • Polycomb Group Protein Complexes
    • Polycomb Response Elements of Drosophila
    • Polycomb Response Elements as Cellular Memory Modules
    • Sequence-Specific DNA-Binding Proteins Implicated in PRE Function
    • PREs as DNA Platforms for Cooperative Recruitment of PcG Complexes
    • Parallels Between Polycomb Targeting in Drosophila and Mammals
    • Conclusion
    • List of Acronyms and Abbreviations
    • Glossary
  • Chapter 7. Polycomb Function and Nuclear Organization
    • Introduction
    • Polycomb Complexes and Their Action on Chromatin
    • Polycomb Domains
    • Polycomb and Chromatin Compaction
    • Polycomb Group Target Loci Form Dynamic Multilooped Three-Dimensional Structures
    • Polycomb-Repressed Domains Form a Subset of Topologically Associating Domains
    • Long-Range Chromosomal Interactions and Three-Dimensional Gene Networks
    • Potential Role for Noncoding RNA in Polycomb Group–Dependent Three-Dimensional Organization
    • Polycomb and Three-Dimensional Genomics in Cancer and Other Diseases
    • Concluding Remarks
    • List of Acronyms and Abbreviations
  • Chapter 8. Molecular Architecture of the Polycomb Repressive Complex 2
    • Introduction
    • PRC2 Electron Microscopy Studies
    • PRC2 X-ray Crystallography Studies
    • Mechanism of H3K27M Inhibition
    • Mechanism of H3K27me3 Activation
    • Summary and Outlook
    • List of Acronyms and Abbreviations
  • Chapter 9. Polycomb Repressive Complex 2 Structure and Function
    • Introduction: Discovery of PRC2
    • PRC2 Evolutionary Conservation
    • The PRC2 Core Complex
    • PRC2 Cofactors
    • PRC2 Within the Polycomb Machinery
    • Concluding Remarks: On the Deterministic or Responsive Role of PRC2 in Transcriptional Regulation
    • List of Acronyms and Abbreviations
  • Chapter 10. Regulation of PRC2 Activity
    • Polycomb Repressive Complex 2 and Its Enzymatic Activity
    • Role of H3K27 Methylation
    • Embryonic Ectoderm Development Facilitates the Propagation of H3K27 Methylation
    • Polycomb Repressive Complex 2 Is Stimulated by Dense Chromatin
    • Cross Talk Among Histone Modifications
    • Accessory Components Modulate Polycomb Repressive Complex 2 Activity
    • H3K27M Inhibits Polycomb Repressive Complex 2 Activity and Leads to Pediatric Glioblastoma
    • Conclusion
    • List of Acronyms and Abbreviations
    • Glossary
  • Chapter 11. Activating Mutations of the EZH2 Histone Methyltransferase in Cancer
    • Introduction to Chromatin and EZH2
    • Amplification and Overexpression of EZH2 in Cancer
    • Regulation of Normal B-Cell Differentiation by EZH2
    • Mutation and Biochemical Activity of EZH2
    • Discovery of Additional Gain-of-Function EZH2 Mutations
    • Structural Rationale for Altered Substrate Specificity in EZH2 Mutants
    • Cellular Activity of EZH2 Mutants
    • Loss-of-Function EZH2 Mutations Commonly Occur in Myeloid Malignancies
    • Discovery of EZH2 Inhibitors
    • Mechanistic and Phenotypic Effects of EZH2 Inhibitors in Cancer Cells
    • Conclusions
    • List of Acronyms and Abbreviations
  • Chapter 12. PcG Proteins in Caenorhabditis elegans
    • Introduction
    • PRC1
    • PRC2
    • Conclusions
    • List of Acronyms and Abbreviation
  • Chapter 13. Global Functions of PRC2 Complexes
    • Introduction
    • Targeted Silencing Functions
    • Global Functions of PRC2
    • Genomic Distribution of H3K27 Methylation
    • Role of Global H3K27 Methylation
    • The Role of UTX: H3K27 Demethylation or Not?
    • H3K27 Acetylation
    • Roaming Activities
    • The Accessibility Hypothesis
    • Recruitment of PRC2 by a PRC1 Type of Complex
    • Does H2A Ubiquitylation Play a Role in Global PRC2 Activity?
    • Polycomb Repressive Activities
    • Evolutionary Aspects of PRC2 Function
  • Index


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About the Author

Vincenzo Pirrotta

Dr. Pirrotta is a world leader in the area of polycomb group proteins. He attended Harvard University up to a postdoctorate level studying physical chemistry and molecular biology. He joined the new EMBL Laboratory in Heidelberg, studying gene regulation in bacteriophage lambda and then Drosophila molecular genetics. He proceeded from there to the Baylor College of Medicine, studying developmental biology, gene regulation and chromatin organization. After tenure at the University of Geneva, he joined Rutgers University in 2004 as part of a laboratory that studies polycomb proteins, epigenetic silencers, chromatin complexes, genomics and nuclear architecture.

Affiliations and Expertise

Department of Molecular Biology and Biochemistry, Rutgers University, USA