scholarly journals Mammalian PRC1 Complexes: Compositional Complexity and Diverse Molecular Mechanisms

2020 ◽  
Vol 21 (22) ◽  
pp. 8594
Author(s):  
Zhuangzhuang Geng ◽  
Zhonghua Gao
Keyword(s):  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Ring Finger ◽  
Transcription Activation ◽  
Polycomb Group ◽  
Histone H2a ◽  
Catalytic Core ◽  
Associated Proteins ◽  
Regulation Mechanisms ◽  
Polycomb Repressive Complexes

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.

scholarly journals Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells

2007 ◽  
Vol 178 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Martin Leeb ◽  
Anton Wutz
Keyword(s):  
Es Cells ◽  
Embryonic Stem ◽  
Ring Finger ◽  
X Inactivation ◽  
Polycomb Group ◽  
Histone H2a ◽  
Embryonic Cells ◽  
Differentiation Potential ◽  
Developmental Control ◽  
Protein Levels

The Polycomb group (PcG) gene Ring1B has been implicated in the repression of developmental control genes and X inactivation and is essential for embryogenesis. Ring1B protein contains a RING finger domain and functions as an E3 ubiquitin ligase that is crucial for the monoubiquitination of histone H2A (H2AK119ub1). Here, we study the function of Ring1B in mouse embryonic stem (ES) cells. The deletion of Ring1B causes the loss of several PcG proteins, showing an unanticipated function in the regulation of PcG protein levels. Derepression of lineage genes and an aberrant differentiation potential is observed in Ring1B-deficient ES cells. Despite a crucial function of Ring1B in establishing the chromosome-wide ubiquitination of histone H2A lysine 119 (H2AK119ub1) upon Xist expression in ES cells, the initiation of silencing by Xist is independent of Ring1B. Other chromatin marks associated with the initiation of X inactivation are not affected in Ring1B-deficient cells, suggesting compensation for the loss of Ring1B in X inactivation in contrast to the repression of lineage genes.

scholarly journals Polycomb group proteins in cancer: multifaceted functions and strategies for modulation

NAR Cancer ◽  
2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Sijie Wang ◽  
Sandra C. Ordonez-Rubiano ◽  
Alisha Dhiman ◽  
Guanming Jiao ◽  
Brayden P Strohmier ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Protein Complexes ◽  
Polycomb Group ◽  
Cancer Therapies ◽  
Transcriptional Repressors ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Methyltransferase Activity ◽  
Ubiquitin Ligase Activity ◽  
Polycomb Repressive Complexes

Abstract Polycomb repressive complexes (PRCs) are a heterogenous collection of dozens, if not hundreds, of protein complexes composed of various combinations of subunits. PRCs are transcriptional repressors important for cell-type specificity during development, and as such, are commonly mis-regulated in cancer. PRCs are broadly characterized as PRC1 with histone ubiquitin ligase activity, or PRC2 with histone methyltransferase activity; however, the mechanism by which individual PRCs, particularly the highly diverse set of PRC1s, alter gene expression has not always been clear. Here we review the current understanding of how PRCs act, both individually and together, to establish and maintain gene repression, the biochemical contribution of individual PRC subunits, the mis-regulation of PRC function in different cancers, and the current strategies for modulating PRC activity. Increased mechanistic understanding of PRC function, as well as cancer-specific roles for individual PRC subunits, will uncover better targets and strategies for cancer therapies.

scholarly journals The Polycomb Group Protein EED Interacts with YY1, and Both Proteins Induce Neural Tissue in XenopusEmbryos

2001 ◽  
Vol 21 (4) ◽  
pp. 1360-1369 ◽  
Author(s):  
David P. E. Satijn ◽  
Karien M. Hamer ◽  
Jan den Blaauwen ◽  
Arie P. Otte
Keyword(s):  
Target Genes ◽  
Protein Complexes ◽  
Neural Induction ◽  
Neural Tissue ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Neural Axis ◽  
Associated Proteins ◽  
Group Protein ◽  
Multimeric Protein

ABSTRACT Polycomb group (PcG) proteins form multimeric protein complexes which are involved in the heritable stable repression of genes. Previously, we identified two distinct human PcG protein complexes. The EED-EZH protein complex contains the EED and EZH2 PcG proteins, and the HPC-HPH PcG complex contains the HPC, HPH, BMI1, and RING1 PcG proteins. Here we show that YY1, a homolog of theDrosophila PcG protein pleiohomeotic (Pho), interacts specificially with the human PcG protein EED but not with proteins of the HPC-HPH PcG complex. Since YY1 and Pho are DNA-binding proteins, the interaction between YY1 and EED provides a direct link between the chromatin-associated EED-EZH PcG complex and the DNA of target genes. To study the functional significance of the interaction, we expressed the Xenopus homologs of EED and YY1 inXenopus embryos. Both Xeed and XYY1 induce an ectopic neural axis but do not induce mesodermal tissues. In contrast, members of the HPC-HPH PcG complex do not induce neural tissue. The exclusive, direct neuralizing activity of both the Xeed and XYY1 proteins underlines the significance of the interaction between the two proteins. Our data also indicate a role for chromatin-associated proteins, such as PcG proteins, in Xenopus neural induction.

scholarly journals Evolution of the D. melanogaster chromatin landscape and its associated proteins

2018 ◽  
Author(s):  
Elise Parey ◽  
Anton Crombach
Keyword(s):  
Protein Complexes ◽  
Replication Timing ◽  
Fruit Fly ◽  
Biochemical Properties ◽  
Polycomb Group ◽  
A Genome ◽  
Wide Range ◽  
Associated Proteins ◽  
Binary Division ◽  
Inference Methods

AbstractIn the nucleus of eukaryotic cells, genomic DNA associates with numerous protein complexes and RNAs, forming the chromatin landscape. Through a genome-wide study of chromatin-associated proteins in Drosophila cells, five major chromatin types were identified as a refinement of the traditional binary division into hetero- and euchromatin. These five types are defined by distinct but overlapping combinations of proteins and differ in biological and biochemical properties, including transcriptional activity, replication timing and histone modifications. In this work, we assess the evolutionary relationships of chromatin-associated proteins and present an integrated view of the evolution and conservation of the fruit fly D. melanogaster chromatin landscape. We combine homology prediction across a wide range of species with gene age inference methods to determine the origin of each chromatin-associated protein. This provides insight into the emergence of the different chromatin types. Our results indicate that the two euchromatic types, YELLOW and RED, were one single activating type that split early in eukaryotic history. Next, we provide evidence that GREEN-associated proteins are involved in a centromere drive and expanded in a lineage-specific way in D. melanogaster. Our results on BLUE chromatin support the hypothesis that the emergence of Polycomb Group proteins is linked to eukaryotic multicellularity. In light of these results, we discuss how the regulatory complexification of chromatin links to the origins of eukaryotic multicellularity.

Current understanding of plant Polycomb group proteins and the repressive histone H3 Lysine 27 trimethylation

2020 ◽  
Vol 48 (4) ◽  
pp. 1697-1706
Author(s):  
Huijun Jiao ◽  
Yuanyuan Xie ◽  
Zicong Li
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Close Association ◽  
Histone H3 ◽  
Polycomb Group ◽  
Dynamic Regulation ◽  
Trithorax Group ◽  
Repressive Mark

Polycomb group (PcG) proteins are highly conserved chromatin-modifying complexes that implement gene silencing in higher eukaryotes. Thousands of genes and multiple developmental processes are regulated by PcG proteins. As the first chromatin modifier been identified in model plant Arabidopsis thaliana, the methyltransferase CURLY LEAF (CLF) and its catalyzed histone H3 Lysine 27 trimethylation (H3K27me3) have already become well-established paradigm in plant epigenetic study. Like in animals, PcG proteins mediate plant development and repress homeotic gene expression by antagonizing with trithorax group proteins. Recent researches have advanced our understanding on plant PcG proteins, including the plant-specific components of these well-conserved protein complexes, the close association with transcription factors and noncoding RNA for the spatial and temporal specificity, the dynamic regulation of the repressive mark H3K27me3 and the PcG-mediated chromatin conformation alterations in gene expression. In this review, we will summarize the molecular mechanisms of PcG-implemented gene repression and the relationship between H3K27me3 and another repressive mark histone H2A Lysine 121 mono-ubiquitination (H2A121ub) will also be discussed.

scholarly journals PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Mitsuhiro Endoh ◽  
Takaho A Endo ◽  
Jun Shinga ◽  
Katsuhiko Hayashi ◽  
Anca Farcas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cell ◽  
Target Genes ◽  
Embryonic Stem ◽  
Ring Finger ◽  
Mouse Embryonic Stem Cells ◽  
Polycomb Group ◽  
Histone H2a ◽  
Cell Growth And Viability

The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.

scholarly journals PWWP INTERACTOR OF POLYCOMBS (PWO1) links PcG-mediated gene repression to the nuclear lamina inArabidopsis

2017 ◽  
Author(s):  
Pawel Mikulski ◽  
Mareike L. Hohenstatt ◽  
Sara Farrona ◽  
Cezary Smaczniak ◽  
Kerstin Kaufmann ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Target Genes ◽  
Protein Complexes ◽  
Nuclear Lamina ◽  
Polycomb Group ◽  
Gene Repression ◽  
Polycomb Repressive Complex 2 ◽  
Peripheral Protein ◽  
Wide Range ◽  
Associated Proteins

AbstractPolycomb group (PcG) proteins facilitate chromatin-mediated gene repression through the modification of histone tails in a wide range of eukaryotes, including plants and animals. One of the PcG protein complexes, Polycomb Repressive Complex 2 (PRC2), promotes repressive chromatin formation via tri-methylation of lysine-27 on histone H3 (H3K27me3). The animal PRC2 is implicated in impacting subnuclear distribution of chromatin as its complex components and H3K27me3 are functionally connected with the nuclear lamina (NL) - a peripheral protein mesh that resides underneath the inner nuclear membrane (INM) and consists of lamins and lamina-associated proteins. In contrast to animals, NL in plants has an atypical structure and its association with PRC2-mediated gene repression is largely unknown. Here, we present a connection between lamin-like protein, CROWDED NUCLEI 1 (CRWN1), and a novel PRC2-associated component, PWWP INTERACTOR OF POLYCOMBS 1 (PWO1), inArabidopsis thaliana. We show that PWO1 and CRWN1 proteins associate physically with each other, act in the same pathway to maintain nuclear morphology and control expression of similar set of target genes. Moreover, we demonstrate that PWO1 proteins form speckle-like foci located partially at the subnuclear periphery inNicotiana benthamianaandArabidopsis thaliana. Ultimately, as CRWN1 and PWO1 are plant-specific, our results argue that plants developed an equivalent, rather than homologous, mechanism of linking PRC2-mediated chromatin repression and nuclear lamina.

scholarly journals Requirement for Three Novel Protein Complexes in the Absence of the Sgs1 DNA Helicase in Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 103-118 ◽  
Author(s):  
Janet R Mullen ◽  
Vivek Kaliraman ◽  
Samer S Ibrahim ◽  
Steven J Brill
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genome Stability ◽  
Protein Complexes ◽  
Ring Finger ◽  
Dna Helicase ◽  
Open Reading Frames ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Dna Helicases ◽  
Cell Extracts

Abstract The Saccharomyces cerevisiae Sgs1 protein is a member of the RecQ family of DNA helicases and is required for genome stability, but not cell viability. To identify proteins that function in the absence of Sgs1, a synthetic-lethal screen was performed. We obtained mutations in six complementation groups that we refer to as SLX genes. Most of the SLX genes encode uncharacterized open reading frames that are conserved in other species. None of these genes is required for viability and all SLX null mutations are synthetically lethal with mutations in TOP3, encoding the SGS1-interacting DNA topoisomerase. Analysis of the null mutants identified a pair of genes in each of three phenotypic classes. Mutations in MMS4 (SLX2) and SLX3 generate identical phenotypes, including weak UV and strong MMS hypersensitivity, complete loss of sporulation, and synthetic growth defects with mutations in TOP1. Mms4 and Slx3 proteins coimmunoprecipitate from cell extracts, suggesting that they function in a complex. Mutations in SLX5 and SLX8 generate hydroxyurea sensitivity, reduced sporulation efficiency, and a slow-growth phenotype characterized by heterogeneous colony morphology. The Slx5 and Slx8 proteins contain RING finger domains and coimmunoprecipitate from cell extracts. The SLX1 and SLX4 genes are required for viability in the presence of an sgs1 temperature-sensitive allele at the restrictive temperature and Slx1 and Slx4 proteins are similarly associated in cell extracts. We propose that the MMS4/SLX3, SLX5/8, and SLX1/4 gene pairs encode heterodimeric complexes and speculate that these complexes are required to resolve recombination intermediates that arise in response to DNA damage, during meiosis, and in the absence of SGS1/TOP3.

scholarly journals Transcriptome and proteome analysis suggest enhanced photosynthesis in tetraploid Liriodendron sino-americanum

2021 ◽  
Author(s):  
Tingting Chen ◽  
Yu Sheng ◽  
Zhaodong Hao ◽  
Xiaofei Long ◽  
Fangfang Fu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Proteome Analysis ◽  
Tree Height ◽  
Photosynthetic Electron Transport ◽  
Industrial Applications ◽  
Chlorophyll Protein Complexes ◽  
Chlorophyll Protein ◽  
Photosynthesis Genes ◽  
Underlying Mechanisms

Abstract Polyploidy generally provides an advantage in phenotypic variation and growth vigor. However, the underlying mechanisms remain poorly understood. The tetraploid L. sino-americanum exhibits altered morphology compared to its diploid counterpart, including larger, thicker and deeper green leaves, bigger stomata, thicker stems and increased tree height. Such characteristics can be useful in ornamental and industrial applications. To elucidate the molecular mechanisms behind this variation, we performed a comparative transcriptome and proteome analysis. Our transcriptome data indicated that some photosynthesis genes and pathways were differentially altered and enriched in tetraploid L. sino-americanum, mainly related to F-type ATPase, the cytochrome b6/f complex, photosynthetic electron transport, the light harvesting chlorophyll protein complexes, photosystem I and II. Most of the differentially expressed proteins we could identify are also involved in photosynthesis. Our physiological results showed that tetraploids have an enhanced photosynthetic capacity, concomitant with great levels of sugar and starch in leaves. This suggests that tetraploid L. sino-americanum might experience comprehensive transcriptome reprogramming of genes related to photosynthesis. This study has especially emphasized molecular changes involved in photosynthesis that accompany polyploidy, and provides a possible explanation for the altered phenotype of polyploidy plants in comparison to their diploid form.

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