scholarly journals Loss of Polycomb Repressive Complex 2 Function Alters Digestive Organ Homeostasis and Neuronal Differentiation in Zebrafish

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3142
Author(s):  
Ludivine Raby ◽  
Pamela Völkel ◽  
Shaghayegh Hasanpour ◽  
Julien Cicero ◽  
Robert-Alain Toillon ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Transcriptional Repression ◽  
Loss Of Function ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Gene Coding ◽  
Development And Differentiation ◽  
Cellular Identity ◽  
The Brain

Polycomb repressive complex 2 (PRC2) mediates histone H3K27me3 methylation and the stable transcriptional repression of a number of gene expression programs involved in the control of cellular identity during development and differentiation. Here, we report on the generation and on the characterization of a zebrafish line harboring a null allele of eed, a gene coding for an essential component of the PRC2. Homozygous eed-deficient mutants present a normal body plan development but display strong defects at the level of the digestive organs, such as reduced size of the pancreas, hepatic steatosis, and a loss of the intestinal structures, to die finally at around 10–12 days post fertilization. In addition, we found that PRC2 loss of function impairs neuronal differentiation in very specific and discrete areas of the brain and increases larval activity in locomotor assays. Our work highlights that zebrafish is a suited model to study human pathologies associated with PRC2 loss of function and H3K27me3 decrease.

scholarly journals Zebrafish Polycomb repressive complex-2 critical roles are largely Ezh2- over Ezh1-driven and concentrate during early embryogenesis

2021 ◽  
Author(s):  
Gabriel A. Yette ◽  
Scott Stewart ◽  
Kryn Stankunas
Keyword(s):  
Cell Fate ◽  
Transcriptional Repression ◽  
Axial Skeleton ◽  
Early Embryogenesis ◽  
Loss Of Function ◽  
Allelic Series ◽  
Polycomb Repressive Complex ◽  
Genetic Studies ◽  
Polycomb Repressive Complex 2 ◽  
Early Developmental

ABSTRACTPolycomb repressive complex-2 (PRC2) methylation of histone H3 lysine-27 (H3K27me) is associated with stable transcriptional repression. PRC2 famously silences Hox genes to maintain anterior-posterior segment identities but also enables early cell fate specification, restrains progenitor cell differentiation, and canalizes cell identities. Zebrafish PRC2 genetic studies have focused on ezh2, which, with its paralog ezh1, encodes the H3K27 methyltransferase component. ezh2 loss-of-function mutants reinforce essential vertebrate PRC2 functions during early embryogenesis albeit with limited contributions to body plan establishment. However, redundancy with ezh1 and the lethality of maternal-zygotic homozygous ezh2 nulls could obscure additional early developmental and organogenesis roles of PRC2. Here, we combine new and existing zebrafish ezh1 and ezh2 alleles to show collective maternal/zygotic ezh2 exclusively provides earliest embryonic PRC2 H3K27me3 activity. Zygotic ezh1, which becomes progressively expressed as ezh2 levels dissipate, has minor redundant and noncompensatory larval roles but itself is not required for viability or fertility. Zygotic Ezh2/PRC2 promotes correct craniofacial bone shape and size by maintaining proliferative pre-osteoblast pools. An ezh2 allelic series including disrupted maternal ezh2 uncovers axial skeleton homeotic transformations and pleiotropic organogenesis defects. Further, once past a critical early window, we show zebrafish can develop near normally with minimal bulk H3K27me3. Our results suggest Ezh2-containing PRC2 stabilizes rather than instructs early developmental decisions while broadly contributing to organ size and embellishment.

scholarly journals Post-translational modifications of PRC2: signals directing its activity

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yiqi Yang ◽  
Gang Li
Keyword(s):  
Catalytic Activity ◽  
Transcriptional Repression ◽  
Essential Role ◽  
Histone H3 ◽  
Post Translational Modifications ◽  
Polycomb Repressive Complex 2 ◽  
Cellular Identity ◽  
Organismal Development ◽  
Biochemical Signals ◽  
Insight Into

Abstract Polycomb repressive complex 2 (PRC2) is a chromatin-modifying enzyme that catalyses the methylation of histone H3 at lysine 27 (H3K27me1/2/3). This complex maintains gene transcriptional repression and plays an essential role in the maintenance of cellular identity as well as normal organismal development. The activity of PRC2, including its genomic targeting and catalytic activity, is controlled by various signals. Recent studies have revealed that these signals involve cis chromatin features, PRC2 facultative subunits and post-translational modifications (PTMs) of PRC2 subunits. Overall, these findings have provided insight into the biochemical signals directing PRC2 function, although many mysteries remain.

scholarly journals 15 Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and the Polycomb Repressive Complex 2

Apmis ◽  
2008 ◽  
Vol 116 (5) ◽  
pp. 424-424
Author(s):  
Diego Pasini ◽  
Klaus H. Hansen ◽  
Jesper Christensen ◽  
Karl Agger ◽  
Paul A. C. Cloos ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Coordinated Regulation

scholarly journals 15Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and the Polycomb Repressive Complex 2

Apmis ◽  
2008 ◽  
Vol 116 (5) ◽  
pp. 424-424
Author(s):  
Diego Pasini ◽  
Klaus H. Hansen ◽  
Jesper Christensen ◽  
Karl Agger ◽  
Paul A. C. Cloos ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2

scholarly journals Peritoneal Modulators of EZH2-miR-155 Cross-Talk in Endometriosis

2021 ◽  
Vol 22 (7) ◽  
pp. 3492
Author(s):  
Sarah Brunty ◽  
Kristeena Ray Wright ◽  
Brenda Mitchell ◽  
Nalini Santanam
Keyword(s):  
Differential Expression ◽  
Cross Talk ◽  
Chromatin Immunoprecipitation ◽  
Peritoneal Fluid ◽  
Loss Of Function ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Histone 3 ◽  
Binding Partners ◽  
Complex Components

Activation of trimethylation of histone 3 lysine 27 (H3K27me3) by EZH2, a component of the Polycomb repressive complex 2 (PRC2), is suggested to play a role in endometriosis. However, the mechanism by which this complex is dysregulated in endometriosis is not completely understood. Here, using eutopic and ectopic tissues, as well as peritoneal fluid (PF) from IRB-approved and consented patients with and without endometriosis, the expression of PRC2 complex components, JARID2, miR-155 (known regulators of EZH2), and a key inflammatory modulator, FOXP3, was measured. A higher expression of EZH2, H3K27me3, JARID2, and FOXP3 as well as miR-155 was noted in both the patient tissues and in endometrial PF treated cells. Gain-or-loss of function of miR-155 showed an effect on the PRC2 complex but had little effect on JARID2 expression, suggesting alternate pathways. Chromatin immunoprecipitation followed by qPCR showed differential expression of PRC2 complex proteins and its associated binding partners in JARID2 vs. EZH2 pull down assays. In particular, endometriotic PF treatment increased the expression of PHF19 (p = 0.0474), a gene silencer and co-factor that promotes PRC2 interaction with its targets. Thus, these studies have identified the potential novel crosstalk between miR-155-PRC2 complex-JARID2 and PHF19 in endometriosis, providing an opportunity to test other epigenetic targets in endometriosis.

scholarly journals Inhibition of Polycomb Repressive Complex 2 activity reduces trimethylation of H3K27 and affects development in Arabidopsis seedlings

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Veronica Ruta ◽  
Chiara Longo ◽  
Alessandra Boccaccini ◽  
Valentina Noemi Madia ◽  
Francesco Saccoliti ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Transcriptional Control ◽  
Catalytic Subunit ◽  
Human Leukemia ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Human Leukemia Cells ◽  
Suitable Target ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Abstract Background Polycomb repressive complex 2 (PRC2) is an epigenetic transcriptional repression system, whose catalytic subunit (ENHANCER OF ZESTE HOMOLOG 2, EZH2 in animals) is responsible for trimethylating histone H3 at lysine 27 (H3K27me3). In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. Results We show here that the 1,5-bis (3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one compound (RDS 3434), previously reported as an EZH2 inhibitor in human leukemia cells, is active on the Arabidopsis catalytic subunit of PRC2, since treatment with the drug reduces the total amount of H3K27me3 in a dose-dependent fashion. Consistently, we show that the expression level of two PRC2 targets is significantly increased following treatment with the RDS 3434 compound. Finally, we show that impairment of H3K27 trimethylation in Arabidopsis seeds and seedlings affects both seed germination and root growth. Conclusions Our results provide a useful tool for the plant community in investigating how PRC2 affects transcriptional control in plant development.

scholarly journals A Class of Protein-Coding RNAs Binds to Polycomb Repressive Complex 2 and Alters Histone Methylation

2021 ◽  
Vol 11 ◽  
Author(s):  
Meijian Liao ◽  
Xiaolin Sun ◽  
Shoucui Gao ◽  
Yaou Zhang
Keyword(s):  
Network Analysis ◽  
Transcriptional Repression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Polycomb Repressive Complex ◽  
Protein Coding ◽  
Polycomb Repressive Complex 2 ◽  
Rna Immunoprecipitation

Polycomb repressive complex 2 (PRC2) is a multi-subunit protein complex mediating the methylation of lysine 27 on histone H3 and playing an important role in transcriptional repression during tumorigenesis and development. Previous studies revealed that both protein-coding and non-coding RNAs could bind to PRC2 complex. However, the functions of protein-coding RNAs that bind to PRC2 complex in tumor are still unknown. Through data mining and RNA immunoprecipitation (RIP) assay, our study found that there were a class of protein-coding RNAs bound to PRC2 complex and H3 with tri-methylation on lysine 27. The Bayesian gene regulatory network analysis pointed out that these RNAs regulated the expression of PRC2-regulated genes in cancer. In addition, gene set enrichment analysis (GSEA), gene ontology (GO) analysis, and weighted gene co-expression network analysis (WGCNA) also confirmed that these RNAs were associated with histone modification in cancer. We also confirmed that MYO1C, a PRC2-bound transcript, inhibited the modification level of H3K27me3. Further detailed study showed that TMEM117 regulated TSLP expression through EZH2-mediated H3K27me3 modification. Interestingly, the RNA recognition motif of PRC2 complex might help these RNAs bind to the PRC2 complex more easily. The same regulatory pattern was found in mice as well.

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