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Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 31165

Special Issue Editor

Prof. Dr. Pierre-Olivier Angrand

E-Mail Website1 Website2
Guest Editor
Université de Lille, CNRS, INSERM, CHU Lille, Centre Oscar Lambret, UMR 9020–UMR 1277–Canther–Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France
Interests: epigenetics; zebrafish model; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polycomb repressive complexes PRC1 and PRC2 are chromatin-modifying protein complexes involved in the transcriptional repression of hundreds of genes that control development and differentiation processes and are also involved in cancer and stem cell biology. Due to the combinatorial association of their core components and/or association with additional accessory factors that regulate enzymatic activity or genomic targeting, PRCs appear to be extremely diverse in their structure and function. Furthermore, due to the involvement of PRCs in a wide variety of cancers, they are rank highly as important targets of cancer therapy.

The goal of this Special Issue is to present the current knowledge on the structure and function of PRCs, their role in different physiological and pathological processes, as well as rational strategies for drug discovery that targets PRCs.

The formats for submissions include original research reports, reviews, perspectives/opinions, and methodology articles.

Prof. Pierre-Olivier Angrand
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • polycomb repressive complexes
  • PRC1
  • PRC2
  • molecular structure
  • epigenetics
  • stem cell biology
  • cancer
  • drug discovery

Published Papers (7 papers)

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Editorial

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3 pages, 191 KiB  
Editorial
Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2
by Pierre-Olivier Angrand
Int. J. Mol. Sci. 2022, 23(11), 5971; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23115971 - 26 May 2022
Cited by 2 | Viewed by 1778
Abstract
Epigenetic regulation contributes to the control of gene expression programs through local chromatin rearrangements [...] Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)

Review

Jump to: Editorial

17 pages, 1049 KiB  
Review
Pathogenic Impacts of Dysregulated Polycomb Repressive Complex Function in Hematological Malignancies
by Satoshi Kaito and Atsushi Iwama
Int. J. Mol. Sci. 2021, 22(1), 74; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010074 - 23 Dec 2020
Cited by 14 | Viewed by 4011
Abstract
Polycomb repressive complexes (PRCs) are epigenetic regulators that mediate repressive histone modifications. PRCs play a pivotal role in the maintenance of hematopoietic stem cells through repression of target genes involved in cell proliferation and differentiation. Next-generation sequencing technologies have revealed that various hematologic [...] Read more.
Polycomb repressive complexes (PRCs) are epigenetic regulators that mediate repressive histone modifications. PRCs play a pivotal role in the maintenance of hematopoietic stem cells through repression of target genes involved in cell proliferation and differentiation. Next-generation sequencing technologies have revealed that various hematologic malignancies harbor mutations in PRC2 genes, such as EZH2, EED, and SUZ12, and PRC1.1 genes, such as BCOR and BCORL1. Except for the activating EZH2 mutations detected in lymphoma, most of these mutations compromise PRC function and are frequently associated with resistance to chemotherapeutic agents and poor prognosis. Recent studies have shown that mutations in PRC genes are druggable targets. Several PRC2 inhibitors, including EZH2-specific inhibitors and EZH1 and EZH2 dual inhibitors have shown therapeutic efficacy for tumors with and without activating EZH2 mutations. Moreover, EZH2 loss-of-function mutations appear to be attractive therapeutic targets for implementing the concept of synthetic lethality. Further understanding of the epigenetic dysregulation associated with PRCs in hematological malignancies should improve treatment outcomes. Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)
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16 pages, 1439 KiB  
Review
No Easy Way Out for EZH2: Its Pleiotropic, Noncanonical Effects on Gene Regulation and Cellular Function
by Jun Wang and Gang Greg Wang
Int. J. Mol. Sci. 2020, 21(24), 9501; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249501 - 14 Dec 2020
Cited by 42 | Viewed by 7999
Abstract
Enhancer of zeste homolog 2 (EZH2) plays critical roles in a range of biological processes including organ development and homeostasis, epigenomic and transcriptomic regulation, gene repression and imprinting, and DNA damage repair. A widely known function of EZH2 is to serve as an [...] Read more.
Enhancer of zeste homolog 2 (EZH2) plays critical roles in a range of biological processes including organ development and homeostasis, epigenomic and transcriptomic regulation, gene repression and imprinting, and DNA damage repair. A widely known function of EZH2 is to serve as an enzymatic subunit of Polycomb repressive complex 2 (PRC2) and catalyze trimethylation of histone H3 lysine 27 (H3K27me3) for repressing target gene expression. However, an increasing body of evidence demonstrates that EZH2 has many “non-conventional” functions that go beyond H3K27 methylation as a Polycomb factor. First, EZH2 can methylate a number of nonhistone proteins, thereby regulating cellular processes in an H3K27me3-independent fashion. Furthermore, EZH2 relies on both methyltransferase-dependent and methyltransferase-independent mechanisms for modulating gene-expression programs and/or epigenomic patterns of cells. Importantly, independent of PRC2, EZH2 also forms physical interactions with a number of DNA-binding factors and transcriptional coactivators to context-dependently influence gene expression. The purpose of this review is to detail the complex, noncanonical roles of EZH2, which are generally less appreciated in gene and (epi)genome regulation. Because EZH2 deregulation is prevalent in human diseases such as cancer, there is increased dependency on its noncanonical function, which shall have important implications in developing more effective therapeutics. Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)
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18 pages, 1995 KiB  
Review
Mammalian PRC1 Complexes: Compositional Complexity and Diverse Molecular Mechanisms
by Zhuangzhuang Geng and Zhonghua Gao
Int. J. Mol. Sci. 2020, 21(22), 8594; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228594 - 14 Nov 2020
Cited by 40 | Viewed by 5743
Abstract
Polycomb group (PcG) proteins function as vital epigenetic regulators in various biological processes, including pluripotency, development, and carcinogenesis. PcG proteins form multicomponent complexes, and two major types of protein complexes have been identified in mammals to date, Polycomb Repressive Complexes 1 and 2 [...] Read more.
Polycomb group (PcG) proteins function as vital epigenetic regulators in various biological processes, including pluripotency, development, and carcinogenesis. PcG proteins form multicomponent complexes, and two major types of protein complexes have been identified in mammals to date, Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The PRC1 complexes are composed in a hierarchical manner in which the catalytic core, RING1A/B, exclusively interacts with one of six Polycomb group RING finger (PCGF) proteins. This association with specific PCGF proteins allows for PRC1 to be subdivided into six distinct groups, each with their own unique modes of action arising from the distinct set of associated proteins. Historically, PRC1 was considered to be a transcription repressor that deposited monoubiquitylation of histone H2A at lysine 119 (H2AK119ub1) and compacted local chromatin. More recently, there is increasing evidence that demonstrates the transcription activation role of PRC1. Moreover, studies on the higher-order chromatin structure have revealed a new function for PRC1 in mediating long-range interactions. This provides a different perspective regarding both the transcription activation and repression characteristics of PRC1. This review summarizes new advancements regarding the composition of mammalian PRC1 and accompanying explanations of how diverse PRC1-associated proteins participate in distinct transcription regulation mechanisms. Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)
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25 pages, 3934 KiB  
Review
Role of Polycomb Complexes in Normal and Malignant Plasma Cells
by Emmanuel Varlet, Sara Ovejero, Anne-Marie Martinez, Giacomo Cavalli and Jerome Moreaux
Int. J. Mol. Sci. 2020, 21(21), 8047; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218047 - 28 Oct 2020
Cited by 9 | Viewed by 3431
Abstract
Plasma cells (PC) are the main effectors of adaptive immunity, responsible for producing antibodies to defend the body against pathogens. They are the result of a complex highly regulated cell differentiation process, taking place in several anatomical locations and involving unique genetic events. [...] Read more.
Plasma cells (PC) are the main effectors of adaptive immunity, responsible for producing antibodies to defend the body against pathogens. They are the result of a complex highly regulated cell differentiation process, taking place in several anatomical locations and involving unique genetic events. Pathologically, PC can undergo tumorigenesis and cause a group of diseases known as plasma cell dyscrasias, including multiple myeloma (MM). MM is a severe disease with poor prognosis that is characterized by the accumulation of malignant PC within the bone marrow, as well as high clinical and molecular heterogeneity. MM patients frequently develop resistance to treatment, leading to relapse. Polycomb group (PcG) proteins are epigenetic regulators involved in cell fate and carcinogenesis. The emerging roles of PcG in PC differentiation and myelomagenesis position them as potential therapeutic targets in MM. Here, we focus on the roles of PcG proteins in normal and malignant plasma cells, as well as their therapeutic implications. Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)
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15 pages, 1703 KiB  
Review
Molecular Regulation of the Polycomb Repressive-Deubiquitinase
by Cameron J. Reddington, Matthias Fellner, Abigail E. Burgess and Peter D. Mace
Int. J. Mol. Sci. 2020, 21(21), 7837; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217837 - 22 Oct 2020
Cited by 10 | Viewed by 3732
Abstract
Post-translational modification of histone proteins plays a major role in histone–DNA packaging and ultimately gene expression. Attachment of ubiquitin to the C-terminal tail of histone H2A (H2AK119Ub in mammals) is particularly relevant to the repression of gene transcription, and is removed by the [...] Read more.
Post-translational modification of histone proteins plays a major role in histone–DNA packaging and ultimately gene expression. Attachment of ubiquitin to the C-terminal tail of histone H2A (H2AK119Ub in mammals) is particularly relevant to the repression of gene transcription, and is removed by the Polycomb Repressive-Deubiquitinase (PR-DUB) complex. Here, we outline recent advances in the understanding of PR-DUB regulation, which have come through structural studies of the Drosophila melanogaster PR-DUB, biochemical investigation of the human PR-DUB, and functional studies of proteins that associate with the PR-DUB. In humans, mutations in components of the PR-DUB frequently give rise to malignant mesothelioma, melanomas, and renal cell carcinoma, and increase disease risk from carcinogens. Diverse mechanisms may underlie disruption of the PR-DUB across this spectrum of disease. Comparing and contrasting the PR-DUB in mammals and Drosophila reiterates the importance of H2AK119Ub through evolution, provides clues as to how the PR-DUB is dysregulated in disease, and may enable new treatment approaches in cancers where the PR-DUB is disrupted. Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)
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18 pages, 1205 KiB  
Review
Emerging Roles of Single-Cell Multi-Omics in Studying Developmental Temporal Patterning
by Andrea Lopes, Elia Magrinelli and Ludovic Telley
Int. J. Mol. Sci. 2020, 21(20), 7491; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207491 - 11 Oct 2020
Cited by 7 | Viewed by 3370
Abstract
The complexity of brain structure and function is rooted in the precise spatial and temporal regulation of selective developmental events. During neurogenesis, both vertebrates and invertebrates generate a wide variety of specialized cell types through the expansion and specification of a restricted set [...] Read more.
The complexity of brain structure and function is rooted in the precise spatial and temporal regulation of selective developmental events. During neurogenesis, both vertebrates and invertebrates generate a wide variety of specialized cell types through the expansion and specification of a restricted set of neuronal progenitors. Temporal patterning of neural progenitors rests on fine regulation between cell-intrinsic and cell-extrinsic mechanisms. The rapid emergence of high-throughput single-cell technologies combined with elaborate computational analysis has started to provide us with unprecedented biological insights related to temporal patterning in the developing central nervous system (CNS). Here, we present an overview of recent advances in Drosophila and vertebrates, focusing both on cell-intrinsic mechanisms and environmental influences. We then describe the various multi-omics approaches that have strongly contributed to our current understanding and discuss perspectives on the various -omics approaches that hold great potential for the future of temporal patterning research. Full article
(This article belongs to the Special Issue Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2)
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