Polycomb repressive complex 2 in embryonic stem cells: an overview

The transcription factor BTB and CNC homology 1 (Bach1) is expressed in the embryos of mice, but whether Bach1 regulates the self-renewal and early differentiation of human embryonic stem cells (hESCs) is unknown. We report that the deubiquitinase ubiquitin-specific processing protease 7 (Usp7) is a direct target of Bach1, that Bach1 interacts with Nanog, Sox2, and Oct4, and that Bach1 facilitates their deubiquitination and stabilization via the recruitment of Usp7, thereby maintaining stem cell identity and self-renewal. Bach1 also interacts with polycomb repressive complex 2 (PRC2) and represses mesendodermal gene expression by recruiting PRC2 to the genes’ promoters. The loss of Bach1 in hESCs promotes differentiation toward the mesendodermal germ layers by reducing the occupancy of EZH2 and H3K27me3 in mesendodermal gene promoters and by activating the Wnt/β-catenin and Nodal/Smad2/3 signaling pathways. Our study shows that Bach1 is a key determinant of pluripotency, self-renewal, and lineage specification in hESCs.

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RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells

Stem Cell Research ◽

10.1016/j.scr.2015.06.007 ◽

2015 ◽

Vol 15 (1) ◽

pp. 182-189 ◽

Cited By ~ 13

Author(s):

Julien Jean Pierre Maury ◽

Chadi A. EL Farran ◽

Daniel Ng ◽

Yuin-Han Loh ◽

Xuezhi Bi ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Gene Targeting ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Polycomb Repressive Complex ◽

Polycomb Repressive Complex 1

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LncRNAs and PRC2: Coupled Partners in Embryonic Stem Cells

Epigenomes ◽

10.3390/epigenomes3030014 ◽

2019 ◽

Vol 3 (3) ◽

pp. 14 ◽

Cited By ~ 2

Author(s):

Alessandro Fiorenzano ◽

Emilia Pascale ◽

Eduardo Jorge Patriarca ◽

Gabriella Minchiotti ◽

Annalisa Fico

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Single Cell Analysis ◽

Embryonic Stem ◽

Epigenetic Landscape ◽

Polycomb Repressive Complex 2 ◽

Non Coding Rna ◽

Long Non Coding Rna ◽

Rna Genes

The power of embryonic stem cells (ESCs) lies in their ability to self-renew and differentiate. Behind these two unique capabilities is a fine-tuned molecular network that shapes the genetic, epigenetic, and epitranscriptomic ESC plasticity. Although RNA has been shown to be functionally important in only a small minority of long non-coding RNA genes, a growing body of evidence has highlighted the pivotal and intricate role of lncRNAs in chromatin remodeling. Due to their multifaceted nature, lncRNAs interact with DNA, RNA, and proteins, and are emerging as new modulators of extensive gene expression programs through their participation in ESC-specific regulatory circuitries. Here, we review the tight cooperation between lncRNAs and Polycomb repressive complex 2 (PRC2), which is intimately involved in determining and maintaining the ESC epigenetic landscape. The lncRNA-PRC2 partnership is fundamental in securing the fully pluripotent state of ESCs, which must be primed to differentiate properly. We also reflect on the advantages brought to this field of research by the advent of single-cell analysis.

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Ubiquitin E3 Ligase Ring1b/Rnf2 of Polycomb Repressive Complex 1 Contributes to Stable Maintenance of Mouse Embryonic Stem Cells

PLoS ONE ◽

10.1371/journal.pone.0002235 ◽

2008 ◽

Vol 3 (5) ◽

pp. e2235 ◽

Cited By ~ 74

Author(s):

Petra van der Stoop ◽

Erwin A. Boutsma ◽

Danielle Hulsman ◽

Sonja Noback ◽

Mike Heimerikx ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

E3 Ligase ◽

Mouse Embryonic Stem Cells ◽

Polycomb Repressive Complex ◽

Ubiquitin E3 Ligase ◽

Stable Maintenance ◽

Polycomb Repressive Complex 1

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Dynamical modeling of the H3K27 epigenetic landscape in mouse embryonic stem cells

10.1101/2021.09.30.462529 ◽

2021 ◽

Author(s):

Kapil Newar ◽

Eric Fanchon ◽

Daniel Jost

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Target Genes ◽

Quantitative Description ◽

Embryonic Stem ◽

Quantitative Agreement ◽

Mouse Embryonic Stem Cells ◽

Perfect Agreement ◽

Polycomb Repressive Complex 2 ◽

Role Of The Reader

The Polycomb system via the methylation of the lysine 27 of histone H3 (H3K27) plays central roles in the silencing of many lineage-specific genes during development. Recent experimental evidence suggested that the recruitment of histone modifying enzymes like the Polycomb repressive complex 2 (PRC2) at specific sites and their spreading capacities from these sites are key to the establishment and maintenance of a proper epigenomic landscape around Polycomb-target genes. Here, based on previous biochemical knowledge, we turned this hypothesis into a mathematical model that can predict the locus-specific distributions of H3K27 modifications. Within the biological context of mouse embryonic stem cells, our model showed quantitative agreement with experimental profiles of H3K27 acetylation and methylation around Polycomb-target genes in wild-type and mutants. In particular, we demonstrated the key role of the reader-writer module of PRC2 and of the competition between the binding of activating and repressing enzymes in shaping the H3K27 landscape around transcriptional start sites. The predicted dynamics of establishment and maintenance of the repressive trimethylated H3K27 state suggest a slow accumulation, in perfect agreement with experiments. Our approach represents a first step towards a quantitative description of PcG regulation in various cellular contexts and provides a generic framework to better characterize epigenetic regulation in normal or disease situations.

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Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and gene expression in murine embryonic stem cells

10.1101/597674 ◽

2019 ◽

Author(s):

Mohammad B. Aljazi ◽

Yuen Gao ◽

Yan Wu ◽

George I. Mias ◽

Jin He

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Transcription Factors ◽

Embryonic Stem Cells ◽

Cell Signaling ◽

Embryonic Stem ◽

Erk Signaling ◽

Gene Promoters ◽

Polycomb Repressive Complex 2 ◽

Murine Embryonic Stem Cells

SummaryThe recruitment of Polycomb repressive complex 2 (PRC2) to gene promoters is critical for its function in repressing gene expression in murine embryonic stem cells (mESCs). However, previous studies have demonstrated although the expression of early lineage-specific genes is largely repressed, the genome-wide PRC2 occupancy is unexpectedly reduced in naïve mESCs. In this study, we provide evidence to show the FGF/ERK signaling determines the global PRC2 occupancy through regulating the expression of PRC2-recruting factor JARID2 in naïve mESCs. At the transcriptional level, the de-repression of bivalent genes is predominantly determined by the presence of cell signaling-associated transcription factors but not the status of PRC2 occupancy at gene promoters. Hence, this study not only reveals a key molecular mechanism by which the FGF/ERK signaling in regulating the PRC2 occupancy in mESCs, but also elucidates a fundamental question regarding the functional roles of transcription factors and Polycomb-mediated epigenetic mechanisms in transcriptional regulation.

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