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.

The complexity of PRC2 catalysts CLF and SWN in plants

2020 ◽  
Vol 48 (6) ◽  
pp. 2779-2789
Author(s):  
Jie Shu ◽  
Chen Chen ◽  
Chenlong Li ◽  
Yuhai Cui
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Molecular Mechanisms ◽  
Histone H3 ◽  
Catalytic Subunits ◽  
Trithorax Group ◽  
Polycomb Repressive Complex 2 ◽  
Plant Life ◽  
Plant Life Cycle ◽  
Curly Leaf

Polycomb repressive complex 2 (PRC2) is an evolutionally conserved multisubunit complex essential for the development of eukaryotes. In Arabidopsis thaliana (Arabidopsis), CURLY LEAF (CLF) and SWINGER (SWN) are PRC2 catalytic subunits that repress gene expression through trimethylating histone H3 at lysine 27 (H3K27me3). CLF and SWN function to safeguard the appropriate expression of key developmental regulators throughout the plant life cycle. Recent researches have advanced our knowledge of the biological roles and the regulation of the activity of CLF and SWN. In this review, we summarize these recent findings and highlight the redundant and differential roles of CLF and SWN in plant development. Further, we discuss the molecular mechanisms underlying CLF and SWN recruitment to specific genomic loci, as well as their interplays with Trithorax-group (TrxG) proteins in plants.

Chromatin modulation and gene regulation in plants: insight about PRC1 function

2018 ◽  
Vol 46 (4) ◽  
pp. 957-966 ◽  
Author(s):  
Qiannan Wang ◽  
Wen-Hui Shen
Keyword(s):  
Current Knowledge ◽  
Protein Complexes ◽  
Histone H3 ◽  
Short Review ◽  
Polycomb Group ◽  
Trithorax Group ◽  
The Core ◽  
Evolutionarily Conserved ◽  
Trithorax Group Proteins ◽  
Polycomb Repressive Complex 1

In plant and metazoan, Polycomb Group (PcG) proteins play key roles in regulating developmental processes by repression of gene expression. PcG proteins function as multi-protein complexes; among them the best characterized ones are Polycomb Repressive Complex 1 (PRC1) and PRC2. PRC2 catalyzes histone H3 lysine 27 trimethylation (H3K27me3), and PRC1 can bind H3K27me3 and catalyzes H2A monoubiquitination. While the PRC2 components and molecular functions are evolutionarily conserved, varied PRC1 complexes are found and they show high divergences between animals and plants. In addition to the core subunits, an exponentially increasing number of PRC1-associated factors have been identified in Arabidopsis thaliana. Recent studies have also unraveled cross-component interactions and intertwined roles of PRC1 and PRC2 in chromatin modulation. In addition, complexities of interactions and functions between PcG and Trithorax Group proteins have been observed. This short review summarizes up current knowledge to provide insight about repressive functional mechanism of PRC1 and its interplay with other factors.

Molecular Mechanisms Underlying the Anti-Breast Cancer Stem Cell Activity of Pterocladia capillacea and Corallina officinalis Polysaccharides

2021 ◽  
Vol 21 ◽  
Author(s):  
Hebatallah G. Hafez ◽  
Rafat M. Mohareb ◽  
Sohair M. Salem ◽  
Azza A. Matloub ◽  
Emad F. Eskander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Cell Activity ◽  
Sulfated Polysaccharide ◽  
Corallina Officinalis ◽  
Stem Cell Activity ◽  
Mcf 7

Objective: This study aimed to appraise the activity of Pterocladia capillacea and Corallina officinalis polysaccharides against breast cancer stem cells (BCSCs). P. capillacea and C. officinalis polysaccharides were characterized to be sulfated polysaccharide-protein complexes. Methods: Cytotoxicity of the polysaccharides against MDA-MB-231 and MCF-7 cell lines along with their impact on CD44+/CD24− and aldehyde dehydrogenase 1(ALDH1) positive BCSC population were determined. Their effect on gene expression of CSC markers, Wnt/β-catenin and Notch signaling pathways was evaluated. Results: P. capillacea and C. officinalis polysaccharides inhibited the growth of breast cancer cells and reduced BCSC subpopulation. P. capillacea polysaccharides significantly down-regulated OCT4, SOX2, ALDH1A3 and vimentin in MDA-MB-231 as well as in MCF-7 cells except for vimentin that was up-regulated in MCF-7 cells. C. officinalis polysaccharides exhibited similar effects except for OCT4 that was up-regulated in MDA-MB-231 cells. Significant suppression of Cyclin D1 gene expression was noted in MDA-MB-231 and MCF-7 cells treated with P. capillacea or C. officinalis polysaccharides. β-catenin and c-Myc genes were significantly down-regulated in MDA-MB-231 cells treated with C. officinalis and P. capillacea polysaccharides, respectively, while being up-regulated in MCF-7 cells treated with either of them. Additionally, P. capillacea and C. officinalis polysaccharides significantly down-regulated Hes1 gene in MCF-7 cells despite increasing Notch1 gene expression level. However, significant down-regulation of Notch1 gene was observed in MDA-MB-231 cells treated with P. capillacea polysaccharides. Conclusion: Collectively, this study provides evidence for the effectiveness of P. capillacea and C. officinalis polysaccharides in targeting BCSCs through interfering with substantial signaling pathways contributing to their functionality.

Maintenance of the active and inactive states

2019 ◽  
pp. 80-92
Author(s):  
John C. Lucchesi
Keyword(s):  
Transcriptional Repression ◽  
Homologous Chromosome ◽  
Regulatory Region ◽  
Histone H3 ◽  
Epigenetic Modifications ◽  
Polycomb Group ◽  
Histone H2a ◽  
Trithorax Group ◽  
Non Coding Rnas ◽  
Somatic Pairing

The maintenance of a gene in an active or inactive state is carried out by epigenetic modifications of the histones and of the DNA itself. Two major classes of complexes (PRC1 and PRC2), containing Polycomb group (PcG) proteins mediate transcriptional repression. PRC2 trimethylates histone H3 at lysine 27, a modification that attracts PRC1 leading to the ubiquitination of histone H2A. Variant PRC1 complexes can be targeted first, and mono-ubiquitinated histone H2A recruits PRC2 complexes that serve as the target for canonical PRC1 complexes. PRC2 can be targeted to sites of repression by associating with long non-coding RNAs. Trithorax group (TrxG) proteins form complexes that counteract PcG-mediated repression. Some subunits of these complexes maintain and enhance transcription by carrying out different lysine methylations (H3K4me, H3K36me and H3K79me) that are associated with active gene function; other subunits remodel chromatin by displacing and repositioning nucleosomes. Additional effects on transcription are transvections, whereby somatic pairing allows the regulatory region of one allele of a gene to influence the activity of the promoter of the allele on the homologous chromosome

NUP98-MLL fusion in human acute myeloblastic leukemia

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2332-2335 ◽  
Author(s):  
Sophie Kaltenbach ◽  
Gwendoline Soler ◽  
Carole Barin ◽  
Carine Gervais ◽  
Olivier A. Bernard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fusion Protein ◽  
Histone H3 ◽  
Cellular Transformation ◽  
Human Leukemia ◽  
Trithorax Group ◽  
Group Protein ◽  
Hoxa Genes ◽  
Hoxa Gene Expression ◽  
Methylation Activity

Abstract Posttranscriptional modifications of histones play important roles in the control of chromatin structure and transcription. H3K4 (histone H3 lysine 4) methylation by the SET domain of the trithorax-group protein MLL (mixed-lineage leukemia) is important for the control of homeobox (HOX) gene expression during development. MLL is tethered to the HOXA locus through interaction of its amino-terminus with menin. MLL fusion proteins associated with human leukemia contain the menin interaction peptide and frequently recruit H3K79 (histone H3 lysine 79) methylation activity. This allows sustained expression of HOXA genes important for cellular transformation. We have characterized a novel recurrent chromosomal aberration, inv(11)(p15q23), as an isolated chromosomal abnormality in 2 patients with acute myeloid leukemia. This aberration is predicted to result in the expression of an NUP98 (nucleoporin 98 kDa)–MLL fusion protein that is unable to interact with menin. As expected, low levels of HOXA gene expression were observed in the patients' samples. This fusion protein is predicted to participate in cellular transformation by activating MLL targets other than HOXA genes.

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 Developmentally regulated alterations in Polycomb repressive complex 1 proteins on the inactive X chromosome

2004 ◽  
Vol 167 (6) ◽  
pp. 1025-1035 ◽  
Author(s):  
Kathrin Plath ◽  
Dale Talbot ◽  
Karien M. Hamer ◽  
Arie P. Otte ◽  
Thomas P. Yang ◽  
...  
Keyword(s):  
X Chromosome ◽  
Protein Complexes ◽  
Histone H3 ◽  
X Inactivation ◽  
Polycomb Group ◽  
Epigenetic Mark ◽  
Embryonic Cells ◽  
Developmentally Regulated ◽  
Inactive X Chromosome ◽  
Multistep Process

Polycomb group (PcG) proteins belonging to the polycomb (Pc) repressive complexes 1 and 2 (PRC1 and PRC2) maintain homeotic gene silencing. In Drosophila, PRC2 methylates histone H3 on lysine 27, and this epigenetic mark facilitates recruitment of PRC1. Mouse PRC2 (mPRC2) has been implicated in X inactivation, as mPRC2 proteins transiently accumulate on the inactive X chromosome (Xi) at the onset of X inactivation to methylate histone H3 lysine 27 (H3-K27). In this study, we demonstrate that mPRC1 proteins localize to the Xi, and that different mPRC1 proteins accumulate on the Xi during initiation and maintenance of X inactivation in embryonic cells. The Xi accumulation of mPRC1 proteins requires Xist RNA and is not solely regulated by the presence of H3-K27 methylation, as not all cells that exhibit this epigenetic mark on the Xi show Xi enrichment of mPRC1 proteins. Our results implicate mPRC1 in X inactivation and suggest that the regulated assembly of PcG protein complexes on the Xi contributes to this multistep process.

scholarly journals Drosophila Ada2b Is Required for Viability and Normal Histone H3 Acetylation

2004 ◽  
Vol 24 (18) ◽  
pp. 8080-8089 ◽  
Author(s):  
Dai Qi ◽  
Jan Larsson ◽  
Mattias Mannervik
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Protein Complexes ◽  
P53 Protein ◽  
Polytene Chromosomes ◽  
Histone H3 ◽  
Saga Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

ABSTRACT Regulation of chromatin through histone acetylation is an important step in gene expression. The Gcn5 histone acetyltransferase is part of protein complexes, e.g., the SAGA complex, that interact with transcriptional activators, targeting the enzyme to specific promoters and assisting in recruitment of the basal RNA polymerase transcription machinery. The Ada2 protein directly binds to Gcn5 and stimulates its catalytic activity. Drosophila contains two Ada2 proteins, Drosophila Ada2a (dAda2a) and dAda2b. We have generated flies that lack dAda2b, which is part of a Drosophila SAGA-like complex. dAda2b is required for viability in Drosophila, and its deletion causes a reduction in histone H3 acetylation. A global hypoacetylation of chromatin was detected on polytene chromosomes in dAda2b mutants. This indicates that the dGcn5-dAda2b complex could have functions in addition to assisting in transcriptional activation through gene-specific acetylation. Although the Drosophila p53 protein was previously shown to interact with the SAGA-like complex in vitro, we find that p53 induction of reaper gene expression occurs normally in dAda2b mutants. Moreover, dAda2b mutant animals show excessive p53-dependent apoptosis in response to gamma radiation. Based on this result, we speculate that dAda2b may be necessary for efficient DNA repair or generation of a DNA damage signal. This could be an evolutionarily conserved function, since a yeast ada2 mutant is also sensitive to a genotoxic agent.

scholarly journals Characterization of Interactions between the Mammalian Polycomb-Group Proteins Enx1/EZH2 and EED Suggests the Existence of Different Mammalian Polycomb-Group Protein Complexes

1998 ◽  
Vol 18 (6) ◽  
pp. 3586-3595 ◽  
Author(s):  
Richard G. A. B. Sewalt ◽  
Johan van der Vlag ◽  
Marco J. Gunster ◽  
Karien M. Hamer ◽  
Jan L. den Blaauwen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Complexes ◽  
Expression Patterns ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Sex Combs ◽  
Group Protein ◽  
Nuclear Domains ◽  
Z Protein

ABSTRACT In Drosophila melanogaster, thePolycomb-group (PcG) andtrithorax-group (trxG) genes have been identified as repressors and activators, respectively, of gene expression. Both groups of genes are required for the stable transmission of gene expression patterns to progeny cells throughout development. Several lines of evidence suggest a functional interaction between the PcG and trxG proteins. For example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be considered both a PcG and a trxGgene. To better understand the molecular interactions in which the E(z) protein is involved, we performed a two-hybrid screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog ofeed, a murine PcG gene which has extensive homology with the Drosophila PcG gene extra sex combs(esc). Enx1/EZH2 and EED coimmunoprecipitate, indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1. Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins.

scholarly journals Chromatin-enriched RNAs mark active and repressive cis-regulation: an analysis of nuclear RNA-seq

2019 ◽  
Author(s):  
Xiangying Sun ◽  
Zhezhen Wang ◽  
Carlos Perez-Cervantes ◽  
Alex Ruthenburg ◽  
Ivan Moskowitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Specific Gene ◽  
Rna Seq ◽  
Cell Type ◽  
Neighboring Gene ◽  
Cis Regulation ◽  
Nuclear Rna ◽  
Cell Type Specific

AbstractLong noncoding RNAs (lncRNAs) localize in the cell nucleus and influence gene expression through a variety of molecular mechanisms. RNA sequencing of two biochemical fractions of nuclei reveals a unique class of lncRNAs, termed chromatin-enriched nuclear RNAs (cheRNAs) that are tightly bound to chromatin and putatively function to cis-activate gene expression. Until now, a rigorous analytic pipeline for nuclear RNA-seq has been lacking. In this study, we survey four computational strategies for nuclear RNA-seq data analysis and show that a new pipeline, Tuxedo, outperforms other approaches. Tuxedo not only assembles a more complete transcriptome, but also identifies cheRNA with higher accuracy. We have used Tuxedo to analyze gold-standard K562 cell datasets and further characterize the genomic features of intergenic cheRNA (icheRNA) and their similarity to those of enhancer RNA (eRNA). Moreover, we quantify the transcriptional correlation of icheRNA and adjacent genes, and suggest that icheRNA may be the cis-acting transcriptional regulator that is more positively associated with neighboring gene expression than eRNA predicted by state-of-art method or CAGE signal. We also explore two novel genomic associations, suggesting cheRNA may have diverse functions. A possible new role of H3K9me3 modification coincident with icheRNA may be associated with active enhancer derived from ancient mobile elements, while a potential cis-repressive function of antisense cheRNA (as-cheRNA) is likely to be involved in transiently modulating cell type-specific cis-regulation.Author SummaryChromatin-enriched nuclear RNA (cheRNA) is a class of gene regulatory non-coding RNAs. CheRNA provides a powerful way to profile the nuclear transcriptional landscape, especially to profile the noncoding transcriptome. The computational framework presented here provides a reliable approach to identifying cheRNA, and for studying cell-type specific gene regulation. We found that intergenic cheRNA, including intergenic cheRNA with high levels of H3K9me3 (a mark associated with closed/repressed chromatin), may act as a transcriptional activator. In contrast, antisense cheRNA, which originates from the complementary strand of the protein-coding gene, may interact with diverse chromatin modulators to repress local transcription. With our new pipeline, one future challenge will be refining the functional mechanisms of these noncoding RNA classes through exploring their regulatory roles, which are involved in diverse molecular and cellular processes in human and other organisms.

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