Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features

Polycomb Repressive Complex 2 (PRC2) is arguably the best-known plant complex of the Polycomb Group (PcG) pathway, formed by a group of proteins that epigenetically represses gene expression. PRC2-mediated deposition of H3K27me3 has amply been studied in Arabidopsis and, more recently, data from other plant model species has also been published, allowing for an increasing knowledge of PRC2 activities and target genes. How PRC2 molecular functions are regulated and how PRC2 is recruited to discrete chromatin regions are questions that have brought more attention in recent years. A mechanism to modulate PRC2-mediated activity is through its interaction with other protein partners or accessory proteins. Current evidence for PRC2 interactors has demonstrated the complexity of its protein network and how far we are from fully understanding the impact of these interactions on the activities of PRC2 core subunits and on the formation of new PRC2 versions. This review presents a list of PRC2 interactors, emphasizing their mechanistic action upon PRC2 functions and their effects on transcriptional regulation.

PRC2

Polycomb-group proteins

10.3390/epigenomes6010008

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Citations (35)

The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development

Epigenomes (2022)

Chet Hong Loh Gert Jan C. Veenstra

Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs). Following these findings, recent work in the field has begun to explore the roles of different PRC2 variant complexes during different stages of embryonic development, by examining molecular phenotypes of PRC2 mutants in both in vitro (2D and 3D differentiation) and in vivo (knock-out mice) assays, analyzed with modern single-cell omics and biochemical assays. In this review, we discuss the latest findings that uncovered the roles of different PRC2 proteins during cell-fate and lineage specification and extrapolate these findings to define a developmental roadmap for different flavors of PRC2 regulation during mammalian embryonic development.

PRC2

Polycomb-group proteins

Cell fate determination

10.3390/epigenomes6030023

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Citations (31)

Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2 (PRC2)

bioRxiv (Cold Spring Harbor Laboratory) (2017)

Chul‐Hwan Lee Marlene Holder Daniel Grau Ricardo Saldaña-Meyer Rais A. Ganai

Abstract The maintenance of gene expression patterns during metazoan development is carried out, in part, by the actions of the Polycomb Repressive Complex 2 (PRC2). PRC2 catalyzes mono-, di-and trimethylation of histone H3 at lysine 27 (H3K27), with H3K27me2/3 being strongly associated with silenced genes. We demonstrate that EZH1 and EZH2, the two mutually exclusive catalytic subunits of PRC2, are differentially activated by various mechanisms. While both PRC2-EZH1 and PRC2-EZH2 are able to catalyze monomethylation, only PRC2-EZH2 is strongly activated by allosteric modulators and specific chromatin substrates to catalyze di-and trimethylation of H3K27. However, we also show that a PRC2 associated protein, AEBP2, can stimulate the activity of both complexes through a mechanism independent of and additive to allosteric activation. These results have strong implications regarding the cellular requirements for and accompanying adjustments in PRC2 activity, given the difference in the expression of EZH1 and EZH2 upon cellular differentiation.

PRC2

Polycomb-group proteins

10.1101/210542

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Citations (2)

[Protein composition of fragmented rat liver chromatin during postnatal ontogenesis].

PubMed (1978)

Klimenko Ai Malyshev Ab Shevtsova MIa

It was shown that after treatment by Ca2+- and Mg2+-dependent DNAses and subsequent dosed ultrasonication the fractions of active and relatively inactive chromatins isolated from liver cell nuclei of rats differing in age contain all main types of histones, but differ considerably in the relative amounts of individual fractions of these proteins. In all age groups studied the proteins of relatively inactive chromatin are largely histones, while the amount of non-histone proteins is higher in active chromatin. In the course of postnatal development the amount of histones in both chromatin fractions is increased and that of non-histone proteins is decreased. This is probably due to heterochromatization of the chromatin complex in liver cells with ageing. In the course of postnatal ontogenesis the spectrum of non-histone proteins in both chromatin fractions is changed.

Non-histone protein

Histone-modifying enzymes

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Recruitment of Polycomb Repressive Complex 2 is Essential to Suppress the Target Chromatin inArabidopsis

Critical Reviews in Plant Sciences (2016)

Yiqiong Huo Zhiqiang Yan Baoshuai Zhang Xiaoxue Wang

The polycomb group (PcG) proteins play important roles in repressing gene expression by modifying chromatin. PcG proteins usually form multiple protein complexes, such as Polycomb Repressive Complex 1 (PRC1) and PRC2 complexes, to repress gene expression. At least three PRC2 complexes have been identified in Arabidopsis that are required for normal plant development. PRC2 complexes repress gene expression through trimethylating lysine 27 on histone 3. Sequentially, PRC1 complexes recognize and bind to H3K27me3 mark generated by PRC2 complexes and monoubiquitylate lysine 119. However, neither the recruitment of PRC nor the regulation mechanisms of PRC functions are well understood. Recent findings suggest that the recruitment of PRC2 complexes to the target chromatin is not simple. Polycomb Response Elements (PREs) in the promoter regions of several PRC2 target genes, transcriptional factors, long noncoding RNAs (lncRNAs), and PRC2 associated-proteins have been documented to be involved in PRC2 targeting. In this review, we focus on the recent findings on PRC2 targeting and their regulatory roles in plant development by repressing gene expression.

PRC2

Polycomb-group proteins

10.1080/07352689.2016.1245055

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Citations (6)

In vitro Transcription of Partially Deproteinised and Reconstituted Chromatins from Pigeon Erythroid Cells

Differentiation (1976)

K.G. Gasaryan N.B. Andreeva V.I. PENKINA

Transcription

10.1111/j.1432-0436.1976.tb00887.x

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Citations (5)