scholarly journals RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Nathan R Rose ◽  
Hamish W King ◽  
Neil P Blackledge ◽  
Nadezda A Fursova ◽  
Katherine JI Ember ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Histone Modification ◽  
Target Genes ◽  
Embryonic Stem ◽  
Polycomb Group ◽  
Chromatin Domain ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Ubiquitin Ligase Activity ◽  
Inappropriate Gene Expression

Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3 lysine 27 trimethylation (H3K27me3). Without normal histone modification-dependent communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode, rendering target genes susceptible to inappropriate gene expression signals. This suggests that activity-based communication and histone modification-dependent thresholds create a localized form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.

scholarly journals Impact of Genome Architecture Upon the Functional Activation and Repression of Hox Regulatory Landscapes

2019 ◽  
Author(s):  
Eddie Rodríguez-Carballo ◽  
Lucille Lopez-Delisle ◽  
Nayuta Yakushiji-Kaminatsui ◽  
Asier Ullate-Agote ◽  
Denis Duboule
Keyword(s):  
Gene Cluster ◽  
Spatial Organization ◽  
Target Genes ◽  
Polycomb Group ◽  
Chromatin Domain ◽  
Regulatory Sequences ◽  
Distal Limb ◽  
Polycomb Repressive Complex 2 ◽  
Enhancer Sequences ◽  
Regulatory Landscapes

BackgroundThe spatial organization of the mammalian genome relies upon the formation of chromatin domains of various scales. At the level of gene regulation in cis, collections of enhancer sequences define large regulatory landscapes that usually match with the presence of topologically associating domains (TADs). These domains are largely determined by bound CTCF molecules and often contain ranges of enhancers displaying similar or related tissue specificity, suggesting that in some cases such domains may act as coherent regulatory units, with a global on or off state.ResultsBy using the HoxD gene cluster as a paradigm, we investigated the effect of large genomic rearrangements affecting the two TADs flanking this locus, including their fusion into a single chromatin domain. We show that, within a single hybrid TAD, the activation of both proximal and distal limb enhancers initially positioned in either TADs globally occurred as when both TADs are intact. We also show that the timely implementation of distal limb enhancers depends on whether or not target genes had previously responded to proximal enhancers, due to the presence or absence of H3K27me3 marks.ConclusionsFrom this work, we conclude that antagonistic limb proximal and distal enhancers can exert their specificities when positioned into the same TAD and in the absence of their genuine target genes. We also conclude that removing these target genes reduced the coverage of a regulatory landscape by chromatin marks associated with silencing and thus prolonged its activity in time. Since Polycomb group proteins are mainly recruited at the Hox gene cluster, our results suggest that Polycomb Repressive Complex 2 (PRC2) can extend its coverage to far-cis regulatory sequences as long as confined to the neighboring TAD structure.

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 Morphine leads to global genome changes in H3K27me3 levels via a Polycomb Repressive Complex 2 (PRC2) self-regulatory mechanism in mESCs

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Iraia Muñoa-Hoyos ◽  
John A. Halsall ◽  
Manu Araolaza ◽  
Carl Ward ◽  
Idoia Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Embryo Development ◽  
Target Genes ◽  
Regulatory Mechanism ◽  
Embryonic Stem ◽  
Polycomb Repressive Complex ◽  
Chronic Morphine ◽  
Polycomb Repressive Complex 2 ◽  
Genes Encoding ◽  
Pass Through

Abstract Background Environmentally induced epigenetic changes can lead to health problems or disease, but the mechanisms involved remain unclear. Morphine can pass through the placental barrier leading to abnormal embryo development. However, the mechanism by which morphine causes these effects and how they sometimes persist into adulthood is not well known. To unravel the morphine-induced chromatin alterations involved in aberrant embryo development, we explored the role of the H3K27me3/PRC2 repressive complex in gene expression and its transmission across cellular generations in response to morphine. Results Using mouse embryonic stem cells as a model system, we found that chronic morphine treatment induces a global downregulation of the histone modification H3K27me3. Conversely, ChIP-Seq showed a remarkable increase in H3K27me3 levels at specific genomic sites, particularly promoters, disrupting selective target genes related to embryo development, cell cycle and metabolism. Through a self-regulatory mechanism, morphine downregulated the transcription of PRC2 components responsible for H3K27me3 by enriching high H3K27me3 levels at the promoter region. Downregulation of PRC2 components persisted for at least 48 h (4 cell cycles) following morphine removal, though promoter H3K27me3 levels returned to control levels. Conclusions Morphine induces targeting of the PRC2 complex to selected promoters, including those of PRC2 components, leading to characteristic changes in gene expression and a global reduction in H3K27me3. Following morphine removal, enhanced promoter H3K27me3 levels revert to normal sooner than global H3K27me3 or PRC2 component transcript levels. We suggest that H3K27me3 is involved in initiating morphine-induced changes in gene expression, but not in their maintenance. Graphic abstract Model of Polycomb repressive complex 2 (PRC2) and H3K27me3 alterations induced by chronic morphine exposure. Morphine induces H3K27me3 enrichment at promoters of genes encoding core members of the PRC2 complex and is associated with their transcriptional downregulation.

scholarly journals Correction to: ZFP281 recruits polycomb repressive complex 2 to restrict extraembryonic endoderm potential in safeguarding embryonic stem cell pluripotency

2021 ◽  
Author(s):  
Xin Huang ◽  
Nazym Bashkenova ◽  
Jihong Yang ◽  
Dan Li ◽  
Jianlong Wang
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Original Publication ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Extraembryonic Endoderm ◽  
Stem Cell Pluripotency ◽  
Embryonic Stem Cell Pluripotency

In the original publication the labelling in middle and bottom panels of figure 2k is published incorrectly as “Soc17”. The correct labeling is available in this correction as “Sox17”.

scholarly journals Association of BMI1 with Polycomb Bodies Is Dynamic and Requires PRC2/EZH2 and the Maintenance DNA Methyltransferase DNMT1

2005 ◽  
Vol 25 (24) ◽  
pp. 11047-11058 ◽  
Author(s):  
Inmaculada Hernández-Muñoz ◽  
Panthea Taghavi ◽  
Coenraad Kuijl ◽  
Jacques Neefjes ◽  
Maarten van Lohuizen
Keyword(s):  
Dna Methyltransferase ◽  
Pericentric Heterochromatin ◽  
Polycomb Group ◽  
Gene Repression ◽  
Kinetic Properties ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Nuclear Structures ◽  
Stable Maintenance ◽  
Polycomb Bodies

ABSTRACT Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in heritable gene repression. Two main PcG complexes have been characterized. Polycomb repressive complex 2 (PRC2) is thought to be involved in the initiation of gene silencing, whereas Polycomb repressive complex 1 (PRC1) is implicated in the stable maintenance of gene repression. Here, we investigate the kinetic properties of the binding of one of the PRC1 core components, BMI1, with PcG bodies. PcG bodies are unique nuclear structures located on regions of pericentric heterochromatin, found to be the site of accumulation of PcG complexes in different cell lines. We report the presence of at least two kinetically different pools of BMI1, a highly dynamic and a less dynamic fraction, which may reflect BMI1 pools with different binding capacities to these stable heterochromatin domains. Interestingly, PRC2 members EED and EZH2 appear to be essential for BMI1 recruitment to the PcG bodies. Furthermore, we demonstrate that the maintenance DNA methyltransferase DNMT1 is necessary for proper PcG body assembly independent of DNMT-associated histone deacetylase activity. Together, these results provide new insights in the mechanism for regulation of chromatin silencing by PcG proteins and suggest a highly regulated recruitment of PRC1 to chromatin.

scholarly journals Polycomb Repressive Complex 2-mediated histone modification H3K27me3 is associated with embryogenic potential in Norway spruce

2020 ◽  
Vol 71 (20) ◽  
pp. 6366-6378 ◽  
Author(s):  
Miyuki Nakamura ◽  
Rita A Batista ◽  
Claudia Köhler ◽  
Lars Hennig
Keyword(s):  
Histone Modification ◽  
Cell Fate ◽  
Norway Spruce ◽  
Plant Species ◽  
Epigenetic Mark ◽  
Polycomb Repressive Complex ◽  
Embryogenic Potential ◽  
Polycomb Repressive Complex 2 ◽  
Embryonic Callus

Abstract Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT&RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.

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