Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes

Nekrasov, Maxim; Klymenko, Tetyana; Fraterman, Sven; Papp, Bernadett; Oktaba, Katarzyna; Köcher, Thomas; Cohen, Adrian; Stunnenberg, Hendrik G.; Wilm, Matthias; Müller, Jürg

doi:10.1038/sj.emboj.7601837

Cited by 243 publications

(235 citation statements)

References 47 publications

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“…10,28 Recent reports suggest that there are additional PRC2 components, AEBP2, PCLs and JARID2, which function as accessory units regulating the function and enzymatic activity of PRC2 holoenzyme. [29][30][31] Despite the dynamic composition of PRC2, EZH1/2 remains its integral component for catalyzing H3K27 di/trimethylation. 32 EZH1 and EZH2 are two paralogs and PRC2-EZH1/-EZH2 complexes function differently to maintain the repressed state of chromatin.…”

Section: Polycomb Group (Pcg) Proteins: Composition Recruitment and mentioning

confidence: 99%

Multifaceted role of EZH2 in breast and prostate tumorigenesis

2013

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Section: Polycomb Group (Pcg) Proteins: Composition Recruitment and mentioning

confidence: 99%

Multifaceted role of EZH2 in breast and prostate tumorigenesis

2013

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“…For comparison, we also performed double knockdown of the PcG proteins ESC and ESC-like (ESCL) and single knockdown of PCL. ESC and ESCL are alternative core subunits of PRC2 that are essential for PRC2 methyltransferase activity (41), whereas PCL is present in a larger PRC2 complex (42,43) and required for the high levels of H3K27me3 at some Polycomb target genes (43). As we previously showed, simultaneous knockdown of ESC and ESCL abolished H3K27me3 (8,41) and resulted in a very substantial increase of the alternative H3K27ac modification (8) (Fig.…”

Section: Significancementioning

confidence: 99%

Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain

Tie

Banerjee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Drosophila Polycomb (PC), a subunit of Polycomb repressive complex 1 (PRC1), is well known for its role in maintaining repression of the homeotic genes and many others and for its binding to trimethylated histone H3 on Lys 27 (H3K27me3) via its chromodomain. Here, we identify a novel activity of PC: inhibition of the histone acetylation activity of CREB-binding protein (CBP). We show that PC and its mammalian CBX orthologs interact directly with the histone acetyltransferase (HAT) domain of CBP, binding to the previously identified autoregulatory loop, whose autoacetylation greatly enhances HAT activity. We identify a conserved PC motif adjacent to the chromodomain required for CBP binding and show that PC binding inhibits acetylation of histone H3. CBP autoacetylation impairs PC binding in vitro, and PC is preferentially associated with unacetylated CBP in vivo. PC knockdown elevates the acetylated H3K27 (H3K27ac) level globally and at promoter regions of some genes that are bound by both PC and CBP. Conversely, PC overexpression decreases the H3K27ac level in vivo and also suppresses CBP-dependent Polycomb phenotypes caused by overexpression of Trithorax, an antagonist of Polycomb silencing. We find that PC is physically associated with the initiating form of RNA polymerase II (Pol II) and that many promoters co-occupied by PC and CBP are associated with paused Pol II, suggesting that PC may play a role in Pol II pausing. These results suggest that PC/PRC1 inhibition of CBP HAT activity plays a role in regulating transcription of both repressed and active PC-regulated genes.Polycomb | CBP | acetylation | histone H3K27 | Drosophila

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“…A distinct form of the PRC2 complex contains an additional protein: polycomb-like (PCL). This fiveprotein complex (Pcl-PRC2) is responsible for the high levels of H3K27 trimethylation (H3K27me3) around the PREs that are needed to maintain the repressed state (Nekrasov et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Adaptive selection and coevolution at the proteins of the Polycomb repressive complexes in Drosophila

et al. 2015

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JM Calvo-Martín, P Librado, M Aguadé, M Papaceit and C Segarra Polycomb group (PcG) proteins are important epigenetic regulatory proteins that modulate the chromatin state through posttranslational histone modifications. These interacting proteins form multimeric complexes that repress gene expression. Thus, PcG proteins are expected to evolve coordinately, which might be reflected in their phylogenetic trees by concordant episodes of positive selection and by a correlation in evolutionary rates. In order to detect these signals of coevolution, the molecular evolution of 17 genes encoding the subunits of five Polycomb repressive complexes has been analyzed in the Drosophila genus. The observed distribution of divergence differs substantially among and along proteins. Indeed, CAF1 is uniformly conserved, whereas only the established protein domains are conserved in other proteins, such as PHO, PHOL, PSC, PH-P and ASX. Moreover, regions with a low divergence not yet described as protein domains are present, for instance, in SFMBT and SU(Z)12. Maximum likelihood methods indicate an acceleration in the nonsynonymous substitution rate at the lineage ancestral to the obscura group species in most genes encoding subunits of the Pcl-PRC2 complex and in genes Sfmbt, Psc and Kdm2. These methods also allow inferring the action of positive selection in this lineage at genes E(z) and Sfmbt. Finally, the protein interaction network predicted from the complete proteomes of 12 Drosophila species using a coevolutionary approach shows two tight PcG clusters. These clusters include well-established binary interactions among PcG proteins as well as new putative interactions.

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Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes

Cited by 243 publications

References 47 publications

Multifaceted role of EZH2 in breast and prostate tumorigenesis

Multifaceted role of EZH2 in breast and prostate tumorigenesis

Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain

Adaptive selection and coevolution at the proteins of the Polycomb repressive complexes in Drosophila

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