scholarly journals Knowing When to Silence: Roles of Polycomb-Group Proteins in SAM Maintenance, Root Development, and Developmental Phase Transition

2020 ◽  
Vol 21 (16) ◽  
pp. 5871
Author(s):  
Bowen Yan ◽  
Yanpeng Lv ◽  
Chunyu Zhao ◽  
Xiaoxue Wang
Keyword(s):  
Phase Transition ◽  
Root Development ◽  
Target Genes ◽  
Polycomb Group ◽  
Developmental Phase ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Developmental Defects ◽  
Histone 3 ◽  
Polycomb Repressive Complex 1

Polycomb repressive complex 1 (PRC1) and PRC2 are the major complexes composed of polycomb-group (PcG) proteins in plants. PRC2 catalyzes trimethylation of lysine 27 on histone 3 to silence target genes. Like Heterochromatin Protein 1/Terminal Flower 2 (LHP1/TFL2) recognizes and binds to H3K27me3 generated by PRC2 activities and enrolls PRC1 complex to further silence the chromatin through depositing monoubiquitylation of lysine 119 on H2A. Mutations in PcG genes display diverse developmental defects during shoot apical meristem (SAM) maintenance and differentiation, seed development and germination, floral transition, and so on so forth. PcG proteins play essential roles in regulating plant development through repressing gene expression. In this review, we are focusing on recent discovery about the regulatory roles of PcG proteins in SAM maintenance, root development, embryo development to seedling phase transition, and vegetative to reproductive phase transition.

scholarly journals Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes

2011 ◽  
Vol 434 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Gaylor Boulay ◽  
Claire Rosnoblet ◽  
Cateline Guérardel ◽  
Pierre-Olivier Angrand ◽  
Dominique Leprince
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Protein Complexes ◽  
Functional Characterization ◽  
Polycomb Group ◽  
Phd Finger ◽  
Reverse Transcription Pcr ◽  
Tudor Domain ◽  
Self Association ◽  
Polycomb Repressive Complex 1

PcG (Polycomb group) proteins are conserved transcriptional repressors essential to regulate cell fate and to maintain epigenetic cellular memory. They work in concert through two main families of chromatin-modifying complexes, PRC1 (Polycomb repressive complex 1) and PRC2–4. In Drosophila, PRC2 contains the H3K27 histone methyltransferase E(Z) whose trimethylation activity towards PcG target genes is stimulated by PCL (Polycomb-like). In the present study, we have examined hPCL3, one of its three human paralogues. Through alternative splicing, hPCL3 encodes a long isoform, hPCL3L, containing an N-terminal TUDOR domain and two PHDs (plant homeodomains) and a smaller isoform, hPCL3S, lacking the second PHD finger (PHD2). By quantitative reverse transcription–PCR analyses, we showed that both isoforms are widely co-expressed at high levels in medulloblastoma. By co-immunoprecipitation analyses, we demonstrated that both isoforms interact with EZH2 through their common TUDOR domain. However, the hPCL3L-specific PHD2 domain, which is better conserved than PHD1 in the PCL family, is also involved in this interaction and implicated in the self-association of hPCL3L. Finally, we have demonstrated that both hPCL3 isoforms are physically associated with EZH2, but in different complexes. Our results provide the first evidence that the two hPCL3 isoforms belong to different complexes and raise important questions about their relative functions, particularly in tumorigenesis.

scholarly journals USP7 Cooperates with SCML2 To Regulate the Activity of PRC1

2015 ◽  
Vol 35 (7) ◽  
pp. 1157-1168 ◽  
Author(s):  
Emilio Lecona ◽  
Varun Narendra ◽  
Danny Reinberg
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Essential Role ◽  
Target Genes ◽  
Polycomb Group ◽  
Histone H2a ◽  
Polycomb Group Protein ◽  
Specific Component ◽  
Group Protein ◽  
The Common ◽  
Polycomb Repressive Complex 1

USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of Polycomb repressive complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by the association of one of the PCGF homologues (PCGF1 to PCGF6) with the common catalytic subunit RING1B. First, we show that SCML2, a Polycomb group protein that associates with PRC1.2 (containing PCGF2/MEL18) and PRC1.4 (containing PCGF4/BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stabilization of BMI1. Chromatin immunoprecipitation (ChIP) experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes. Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated histone H2A (H2Aub), the catalytic product of PRC1 and key for its repressive activity. USP7 regulates the posttranslational status of RING1B and BMI1, a specific component of PRC1.4. Thus, not only does USP7 stabilize PRC1 components, its catalytic activity is also necessary to maintain a functional PRC1, thereby ensuring appropriate levels of repressive H2Aub.

scholarly journals Polycomb Cbx2 Condensates Assemble through Phase Separation

2018 ◽  
Author(s):  
Roubina Tatavosian ◽  
Samantha Kent ◽  
Kyle Brown ◽  
Tingting Yao ◽  
Huy Nguyen Duc ◽  
...  
Keyword(s):  
Phase Separation ◽  
Polycomb Group ◽  
Developmental Defects ◽  
Intrinsically Disordered ◽  
Condensate Formation ◽  
Development And Differentiation ◽  
Polycomb Repressive Complex 1 ◽  
Liquid Liquid Phase Separation

AbstractPolycomb group (PcG) proteins are master regulators of development and differentiation. Mutation and dysregulation of PcG genes cause developmental defects and cancer. PcG proteins form condensates in the nucleus of cells and these condensates are the physical sites of PcG-targeted gene silencing. However, the physiochemical principles underlying the PcG condensate formation remain unknown. Here we show that Polycomb repressive complex 1 (PRC1) protein Cbx2, one member of the Cbx family proteins, contains a long stretch of intrinsically disordered region (IDR). Cbx2 undergoes phase separation to form condensates. Cbx2 condensates exhibit liquid-like properties and can concentrate DNA and nucleosomes. We demonstrate that the conserved residues within the IDR promote the condensate formation in vitro and in vivo. We further indicate that H3K27me3 has minimal effects on the Cbx2 condensate formation while depletion of core PRC1 subunits facilitates the condensate formation. Thus, our results reveal that PcG condensates assemble through liquid-liquid phase separation (LLPS) and suggest that PcG-bound chromatin is in part organized through phase-separated condensates.

scholarly journals Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Roberto Bonasio ◽  
Emilio Lecona ◽  
Varun Narendra ◽  
Philipp Voigt ◽  
Fabio Parisi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Target Genes ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Binding Region ◽  
Group Protein ◽  
Polycomb Repressive Complex 1

Polycomb repressive complex-1 (PRC1) is essential for the epigenetic regulation of gene expression. SCML2 is a mammalian homolog of Drosophila SCM, a Polycomb-group protein that associates with PRC1. In this study, we show that SCML2A, an SCML2 isoform tightly associated to chromatin, contributes to PRC1 localization and also directly enforces repression of certain Polycomb target genes. SCML2A binds to PRC1 via its SPM domain and interacts with ncRNAs through a novel RNA-binding region (RBR). Targeting of SCML2A to chromatin involves the coordinated action of the MBT domains, RNA binding, and interaction with PRC1 through the SPM domain. Deletion of the RBR reduces the occupancy of SCML2A at target genes and overexpression of a mutant SCML2A lacking the RBR causes defects in PRC1 recruitment. These observations point to a role for ncRNAs in regulating SCML2 function and suggest that SCML2 participates in the epigenetic control of transcription directly and in cooperation with PRC1.

scholarly journals Human heterochromatin protein 1 isoform HP1β enhances androgen receptor activity and is implicated in prostate cancer growth

2010 ◽  
Vol 17 (2) ◽  
pp. 455-467 ◽  
Author(s):  
M Shiota ◽  
Y Song ◽  
A Yokomizo ◽  
Y Tada ◽  
K Kuroiwa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Target Genes ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Heterochromatin Protein 1 ◽  
Promoter Regions ◽  
Heterochromatin Protein ◽  
Castration Resistant ◽  
Androgen Receptor Activity

There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, heterochromatin protein 1β (HP1β), but not HP1α or HP1γ was found to be an AR cofactor. HP1β interacted with the AR, and enhanced the DNA-binding ability of AR to androgen-responsive element in the prostate-specific antigen enhancer and promoter regions, and to increase the transcription of AR target genes. In prostate cancer (PCa) tissues, HP1β expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1β suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, HP1β was overexpressed in castration-resistant LNCaP derivative CxR cells, and HP1β knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1β is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1β expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC.

scholarly journals Plasmodium falciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9 and is linked to mutually exclusive expression of var genes

2009 ◽  
Vol 37 (8) ◽  
pp. 2596-2606 ◽  
Author(s):  
K. Perez-Toledo ◽  
A. P. Rojas-Meza ◽  
L. Mancio-Silva ◽  
N. A. Hernandez-Cuevas ◽  
D. M. Delgadillo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Var Genes ◽  
Histone 3

scholarly journals Polycomb repressive complex 1 defines the nucleosome landscape but not accessibility at target genes

2018 ◽  
Author(s):  
Hamish W King ◽  
Robert J Klose
Keyword(s):  
Target Genes ◽  
Nucleosome Occupancy ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Polycomb Group ◽  
Gene Promoters ◽  
Polycomb Repressive Complex ◽  
Chromatin Domains ◽  
Genetic Ablation ◽  
Polycomb Repressive Complex 1

ABSTRACTPolycomb group (PcG) proteins are transcriptional repressors that play important roles regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin limiting the activity of chromatin remodelling enzymes and access of the transcriptional machinery to DNA. In fitting with these ideas, gene promoters associated with PcG proteins have been reported to be less accessible than other gene promotors. However, it remains largely untested in vivo whether PcG proteins define chromatin accessibility or other chromatin features. To address this important question, we measured chromatin accessibility and examined the nucleosome landscape at PcG protein-bound promoters in mouse embryonic stem cells using the assay for transposase accessible chromatin (ATAC)-seq. Combined with genetic ablation strategies, we unexpectedly discover that although PcG protein-occupied gene promoters exhibit reduced accessibility, this does not rely on PcG proteins. Instead, the Polycomb repressive complex 1 (PRC1) appears to play a unique role in driving elevated nucleosome occupancy and decreased nucleosomal spacing in Polycomb chromatin domains. Our new genome-scale observations argue, in contrast to the prevailing view, that PcG proteins and Polycomb chromatin domains do not significantly affect chromatin accessibility and highlight an underappreciated complexity in the relationship between chromatin accessibility, the nucleosome landscape and PcG-mediated transcriptional repression.

scholarly journals Dynamics of H3K4me3 Chromatin Marks Take the Lead over H3K27me3 for Gene Regulation during Flower Morphogenesis in Arabidopsis thaliana

2017 ◽  
Author(s):  
Julia Engelhorn ◽  
Robert Blanvillain ◽  
Christian Kröner ◽  
Hugues Parrinello ◽  
Marine Rohmer ◽  
...  
Keyword(s):  
Target Genes ◽  
Gene Activation ◽  
Polycomb Group ◽  
Specific Expression ◽  
Tissue Specific ◽  
Trithorax Group ◽  
Flower Morphogenesis ◽  
Histone 3 ◽  
Genome Wide ◽  
Transcriptional Changes

Plant life-long organogenesis involves sequential, time and tissue specific expression of developmental genes. This requires activities of Polycomb Group (PcG) and trithorax Group complexes, respectively responsible for repressive Histone 3 trimethylation at lysine 27 (H3K27me3) and activation-related H3K4me3. However, the genome-wide dynamics in histone modifications that occur during developmental processes have remained elusive. Here, we report the distributions of H3K27me3 and H3K4me3 along with transcriptional changes, in a developmental series including Arabidopsis leaf and three stages of flower development. We found that chromatin mark levels are highly dynamic over the time series on nearly half of all Arabidopsis genes. Moreover, during early flower morphogenesis, changes in H3K4me3 prime over changes in H3K27me3 and quantitatively correlate with transcription changes, while H3K27me3 changes occur after prolonged expression changes. Notably, early activation of PcG target genes is dominated by increases in H3K4me3 while H3K27me3 remains present at the locus. Our results reveal H3K4me3 as greater predictor over H3K27me3 for transcription dynamics, unveil unexpected chromatin mechanisms at gene activation and underline the relevance of tissue-specific temporal epigenomics.

scholarly journals Ctf4-related protein recruits LHP1-PRC2 to maintain H3K27me3 levels in dividing cells in Arabidopsis thaliana

2017 ◽  
Vol 114 (18) ◽  
pp. 4833-4838 ◽  
Author(s):  
Yue Zhou ◽  
Emmanuel Tergemina ◽  
Haitao Cui ◽  
Alexander Förderer ◽  
Benjamin Hartwig ◽  
...  
Keyword(s):  
Cell Division ◽  
Target Genes ◽  
Physical Interaction ◽  
Heterochromatin Protein 1 ◽  
Catalytic Core ◽  
Heterochromatin Protein ◽  
Differentiated Cells ◽  
Chromosome Transmission ◽  
Dividing Cells ◽  
Curly Leaf

Polycomb Repressive Complex (PRC) 2 catalyzes the H3K27me3 modification that warrants inheritance of a repressive chromatin structure during cell division, thereby assuring stable target gene repression in differentiated cells. It is still under investigation how H3K27me3 is passed on from maternal to filial strands during DNA replication; however, cell division can reinforce H3K27me3 coverage at target regions. To identify novel factors involved in the Polycomb pathway in plants, we performed a forward genetic screen for enhancers of the like heterochromatin protein 1 (lhp1) mutant, which shows relatively mild phenotypic alterations compared with other plant PRC mutants. We mapped enhancer of lhp1 (eol) 1 to a gene related to yeast Chromosome transmission fidelity 4 (Ctf4) based on phylogenetic analysis, structural similarities, physical interaction with the CMG helicase component SLD5, and an expression pattern confined to actively dividing cells. A combination of eol1 with the curly leaf (clf) allele, carrying a mutation in the catalytic core of PRC2, strongly enhanced the clf phenotype; furthermore, H3K27me3 coverage at target genes was strongly reduced in eol1 clf double mutants compared with clf single mutants. EOL1 physically interacted with CLF, its partially redundant paralog SWINGER (SWN), and LHP1. We propose that EOL1 interacts with LHP1–PRC2 complexes during replication and thereby participates in maintaining the H3K27me3 mark at target genes.

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