Molecular mechanisms directing PRC2 recruitment and H3K27 methylation
Open accessAbstract
The polycomb repressive complex 2 (PRC2) is a chromatin-associated methyltransferase catalyzing mono-, di-, and trimethylation of lysine 27 on histone H3 (H3K27). This activity is required for normal organismal development and maintenance of gene expression patterns to uphold cell identity. PRC2 function is often deregulated in disease and is a promising candidate for therapeutic targeting in cancer. In this review, we discuss the molecular mechanisms proposed to take part in modulating PRC2 recruitment and shaping H3K27 methylation patterns across the genome. This includes consideration of factors influencing PRC2 residence time on chromatin and PRC2 catalytic activity with a focus on the mechanisms giving rise to regional preferences and differential deposition of H3K27 methylation. We further discuss existing evidence for functional diversity between distinct subsets of PRC2 complexes with the aim of extracting key concepts and highlighting major open questions toward a more complete understanding of PRC2 function.
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EZH2 serves as the catalytic subunit of Polycomb Repressive Complex 2, responsible for depositing the repressive H3K27me3 mark and silencing target genes.
“Within the Polycomb Repressive Complex 2 (PRC2), EZH2 serves as the catalytic subunit responsible for depositing the repressive H3K27me3 mark and silencing target genes (Blackledge et al., 2020; Laugesen et al., 2019).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Laugesen et al., 2019
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Hyperconserved CpG domains underlie Polycomb-binding sites
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MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding
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Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding
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Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2
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EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells
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Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin
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Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
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DNA binding by PHF1 prolongs PRC2 residence time on chromatin and thereby promotes H3K27 methylation
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Nucleosome Turnover Regulates Histone Methylation Patterns over the Genome
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Origins and Formation of Histone Methylation across the Human Cell Cycle
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Lack of Transcription Triggers H3K27me3 Accumulation in the Gene Body
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The PRC2-associated factor C17orf96 is a novel CpG island regulator in mouse ES cells
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Recent Structural Insights into Polycomb Repressive Complex 2 Regulation and Substrate Binding
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Structural analysis of an active fungal PRC2
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Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study
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The molecular principles of gene regulation by Polycomb repressive complexes
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The roles of Polycomb repressive complexes in mammalian development and cancer
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Histone H2AK119 Mono-Ubiquitination Is Essential for Polycomb-Mediated Transcriptional Repression
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Chromatin replication and epigenetic cell memory
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Auxin signaling: Research advances over the past 30 years
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PRC1 catalytic activity is central to polycomb system function
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The Complexity of PRC2 Subcomplexes
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PRC2.1 and PRC2.2 Synergize to Coordinate H3K27 Trimethylation
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Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancerPreprint
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“In addition, several accessory proteins associate with core PRC2, which are thought to modulate the recruitment and enzymatic activity of the complex (Fig. 5A; Laugesen et al. 2019).”
BackgroundRegulation, functions and transmission of bivalent chromatin during mammalian development
Macrae, T. A., Fothergill-Robinson, J., & Ramalho‐Santos, M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00518-2 · Cited by 186 · see citing works
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Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response
Béguelin, W., Teater, M. R., Meydan, C., Hoehn, K. B., Phillip, J. M., Soshnev, A. A., Venturutti, L., Rivas, M. A., Calvo, M. T., Gutierrez, J., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.04.004 · Cited by 161 · see citing works
Histone editing elucidates the functional roles of H3K27 methylation and acetylation in mammals
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Distinct dynamics and functions of H2AK119ub1 and H3K27me3 in mouse preimplantation embryos
Chen, Z., Djekidel, M. N., & Zhang, Y. (2021) · Nature Genetics · doi:10.1038/s41588-021-00821-2 · Cited by 153 · see citing works
RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells
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SOX4: Epigenetic regulation and role in tumorigenesis
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Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming
Kuroda, M. I., Kang, H., De, S., & Kassis, J. A. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-120219-103641 · Cited by 120 · see citing works
“For all of those regulated loci, how does PcG targeting change with cell type (1, 94)?”
BackgroundInfluentialStructural basis for PRC2 decoding of active histone methylation marks H3K36me2/3
Finogenova, K., Bonnet, J., Poepsel, S., Schäfer, I. B., Finkl, K., Schmid, K., Litz, C., Strauss, M., Benda, C., & Müller, J. (2020) · eLife · doi:10.7554/elife.61964 · Cited by 119 · see citing works
“The histone methyltransferase Polycomb Repressive Complex 2 (PRC2) and its regulation by accessory proteins and histone modifications represent a prime example for understanding these interaction mechanisms (Laugesen et al., 2019; Yu et al., 2019).”
PRC2 functions in development and congenital disorders
Deevy, O., & Bracken, A. P. (2019) · Development · doi:10.1242/dev.181354 · Cited by 120 · see citing works
“DNMT, DNA methyltransferase; HMT, histone methyltransferase; mESC, mouse embryonic stem cell; ND, not determined; ?, lack of consensus to date.”
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EZH2 function in immune cell development
Nutt, S. L., Keenan, C. R., Chopin, M., & Allan, R. S. (2020) · Biological Chemistry · doi:10.1515/hsz-2019-0436 · Cited by 110 · see citing works
Going beyond Polycomb: EZH2 functions in prostate cancer
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JMJD family proteins in cancer and inflammation
Wang, M., Jianxin, X., Hong, W., Chen, S., & Huashan, S. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01145-1 · Cited by 103 · see citing works
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PRC2 activity, recruitment, and silencing: a comparative perspective
Bieluszewski, T., Xiao, J. Y., Yang, Y., & Wagner, D. (2021) · Trends in Plant Science · doi:10.1016/j.tplants.2021.06.006 · Cited by 94 · see citing works
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“(H3K27) tri-methylation and transcriptional repression of tumor suppressor genes (Laugesen et al., 2019).”
BackgroundA new role for histone demethylases in the maintenance of plant genome integrity
Antúnez-Sánchez, J., Naish, M., Ramirez-Prado, J. S., Ohno, S., Huang, Y., Dawson, A., Opassathian, K., Manza-Mianza, D., Ariel, F., Raynaud, C., et al. (2020) · eLife · doi:10.7554/elife.58533 · Cited by 84 · see citing works
Epigenetic Therapies for Osteoarthritis
Grandi, F. C., & Bhutani, N. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.05.008 · Cited by 83 · see citing works
Mechanisms of Immunosuppression in Colorectal Cancer
Zhang, Y., Rajput, A., Jin, N. Y., & Wang, J. (2020) · Cancers · doi:10.3390/cancers12123850 · Cited by 81 · see citing works
Polycomb repressive 2 complex—Molecular mechanisms of function
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“Enhancer of zeste homolog 2 (EZH2) is the catalytic core subunit of Polycomb Repressive Complex 2 (PRC2) that can silence target genes through trimethylation of H3K27 [11].”
BackgroundAlabert, C., Loos, C., Voelker-Albert, M., Graziano, S., Forné, I., Reverón-Gómez, N., Schuh, L., Hasenauer, J., Marr, C., Imhof, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.060 · Cited by 76 · see citing works
“In mammalian cells, CpG richness is important for PRC2 recruitment, but a distinct recognition element remains to be identified (Laugesen et al., 2019).”
Neuronal maturation and axon regeneration: unfixing circuitry to enable repair
Hilton, B. J., Griffin, J. M., Fawcett, J. W., & Bradke, F. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00849-3 · Cited by 77 · see citing works
“Selective exclusion of molecules from axons starts with the appearance of the axon initial segment (AIS) , a structure organized by the scaffolding protein ankyrin G.”
Zhang, J., Sui, S., Wu, H., Zhang, J., Zhang, X., Xu, S., & Pang, D. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1835-3 · Cited by 74 · see citing works
Structural basis for inactivation of PRC2 by G-quadruplex RNA
Song, J., Gooding, A. R., Hemphill, W. O., Love, B. D., Robertson, A., Yao, L., Zon, L. I., North, T. E., Kasinath, V., & Cech, T. R. (2023) · Science · doi:10.1126/science.adh0059 · Cited by 73 · see citing works
3D chromatin architecture and transcription regulation in cancer
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“PRC2 is built around core subunits EZH1/2, EED, and SUZ12, in association with the histone-binding RBBP4/7.(15) The histone-methyl-transfer-”
BackgroundInfluentialMolecular Mechanisms of Facultative Heterochromatin Formation: An X-Chromosome Perspective
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AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution
Schade, A. E., Perurena, N., Yang, Y., Rodriguez, C. L., Krishnan, A., Gardner, A., Loi, P., Xu, Y., Nguyen, V. T. M., Mastellone, G. M., et al. (2024) · Nature · doi:10.1038/s41586-024-08031-6 · Cited by 72 · see citing works
Structural basis for PRC2 engagement with chromatin
Glancy, E., Ciferri, C., & Bracken, A. P. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.10.017 · Cited by 68 · see citing works
The role of EZH1 and EZH2 in development and cancer
Lee, S. H., Li, Y., Kim, H., Eum, S., Park, K., & Lee, C. (2022) · BMB Reports · doi:10.5483/bmbrep.2022.55.12.174 · Cited by 65 · see citing works
“The review for PRC2 accessory proteins can be found elsewhere (1, 14, 15, 22).”
BackgroundKumar, S., Kaur, S., Seem, K., Kumar, S., & Mohapatra, T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.774719 · Cited by 66 · see citing works
Triazole-fused pyrimidines in target-based anticancer drug discovery
Dai, X., Xue, L.-P., Ji, S., Zhou, Y., Gao, Y., Zheng, Y., Liu, H., & Liu, H. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115101 · Cited by 63 · see citing works
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Epigenetic and transcriptional mechanisms for the regulation of IL-10
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“H3K9me3 and H3K27me3 are recognized respectively by heterochromatin protein 1 (HP1) and polycomb repressive complex 1 (PRC1) to create compacted heterochromatin[51,52].”
BackgroundSmall Molecule Approaches for Targeting the Polycomb Repressive Complex 2 (PRC2) in Cancer
Martin, M. C., Zeng, G., Yu, J., & Schiltz, G. E. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01344 · Cited by 62 · see citing works
Decoding the protein composition of whole nucleosomes with Nuc-MS
Schachner, L. F., Jooß, K., Morgan, M. A., Piunti, A., Meiners, M. J., Kafader, J. O., Lee, A. S., Iwanaszko, M., Cheek, M. A., Burg, J. M., et al. (2021) · Nature Methods · doi:10.1038/s41592-020-01052-9 · Cited by 66 · see citing works
Regulating Methylation at H3K27: A Trick or Treat for Cancer Cell Plasticity
Das, P., & Taube, J. H. (2020) · Cancers · doi:10.3390/cancers12102792 · Cited by 57 · see citing works
“Detailed reviews concerning the activity and history of the H3K27me3 methyltransferases, EZH1 and EZH2, are available [21,22].”
BackgroundTargeting epigenetic modulators using PROTAC degraders: Current status and future perspective
Webb, T., Craigon, C., & Ciulli, A. (2022) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2022.128653 · Cited by 59 · see citing works
LncRNA SNHG15: A new budding star in human cancers
Shuai, Y., Ma, Z., Lu, J., & Feng, J. (2019) · Cell Proliferation · doi:10.1111/cpr.12716 · Cited by 59 · see citing works
Understanding aberrant RNA splicing to facilitate cancer diagnosis and therapy
Dong, X., & Chen, R. (2019) · Oncogene · doi:10.1038/s41388-019-1138-2 · Cited by 58 · see citing works
The many faces of Polycomb regulation by RNA
Almeida, M. R., Bowness, J. S., & Brockdorff, N. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.02.023 · Cited by 58 · see citing works
Dynamics of H3K27me3 Modification on Plant Adaptation to Environmental Cues
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Bonnet, J., Boichenko, I., Kalb, R., Jeune, M. L., Maltseva, S., Pieropan, M., Finkl, K., Fierz, B., & Müller, J. (2022) · Genes & Development · doi:10.1101/gad.350014.122 · Cited by 57 · see citing works
“H3K27me3 acts as a binding site for the Polycomb (Pc) subunit of canonical PRC1 (Fischle et al. 2003; Min et al. 2003) and is also recognized by the Esc (EED) subunit of PRC2 (Laugesen et al. 2019; Yu et al. 2019).”
InfluentialNuclear condensates of YAP fusion proteins alter transcription to drive ependymoma tumourigenesis
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“EZH2 serves as the core enzymatic subunit of PRC2, a complex that can methylate lysine 27 of histone H3 and facilitates chromatin remodeling and transcriptional silencing [30].”
Ling, T., Birger, Y., Stankiewicz, M. J., Ben-Haim, N., Tomer Kalisky, C., Rein, A., Kugler, E., Chen, W., Fu, C., Zhang, K. X., et al. (2019) · Blood · doi:10.1182/blood.2019001234 · Cited by 54 · see citing works
Activity of PRC1 and Histone H2AK119 Monoubiquitination: Revising Popular Misconceptions
Cohen, I., Bar, C., & Ezhkova, E. (2020) · BioEssays · doi:10.1002/bies.201900192 · Cited by 53 · see citing works
Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy
Rugowska, A., Starosta, A., & Konieczny, P. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01001-z · Cited by 58 · see citing works
“EZH1 and EZH2 are Su(var)3–9, enhancer of zeste, and trithorax catalytic (SET) domaincontaining proteins harboring HKMT activity, while SUZ12 and EED are involved in the PRC2 stability and are required for the EZH1/2 catalytic activities [65, 66].”
BackgroundASXL1/2 mutations and myeloid malignancies
Medina, E. A., Delma, C. R., & Yang, F. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01336-x · Cited by 54 · see citing works
“The core PRC2 subunits associate with equimolar stoichiometries, and all are required for the catalytic activity of the complex [96, 97].”
BackgroundBerry, K., Wang, J., & Lu, Q. R. (2020) · F1000Research · doi:10.12688/f1000research.20904.1 · Cited by 50 · see citing works
Zhang, Y., Chan, H. L., Garcia-Martinez, L., Karl, D. L., Weich, N., Slingerland, J. M., Verdún, R. E., & Morey, L. (2020) · Science Advances · doi:10.1126/sciadv.aaz7249 · Cited by 52 · see citing works
“Although we know much about PRC1 and PRC2 recruitment mechanisms in embryonic stem cells, very little is known in adult stem cells and cancer cells (14, 29).”
BackgroundHarachi, M., Masui, K., Honda, H., Muragaki, Y., Kawamata, T., Cavenee, W. K., Mischel, P. S., & Shibata, N. (2020) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-20-0024 · Cited by 52 · see citing works
Kamei, M., Ameri, A. J., Ferraro, A. R., Bar-Peled, Y., Zhao, F., Ethridge, C. L., Lail, K., Amirebrahimi, M., Lipzen, A., Ng, V., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2010003118 · Cited by 50 · see citing works
Wang, S., Zhang, Q., Ge, X., Li, C., Xue, M., Liang, K., Ma, R., Ouyang, L., Zheng, L., Jing, J., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04142-3 · Cited by 51 · see citing works
“EZH2 is an important catalytic subunit in the PRC2 complex that has methyltransferase activity, can catalyze H3K27me3 formation, and plays an important role in the initial stage of transcriptional repression [48].”
BackgroundLeicher, R., Ge, E. J., Lin, X., Reynolds, M. J., Xie, W. J., Walz, T., Zhang, B., Muir, T. W., & Liu, S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003395117 · Cited by 51 · see citing works
Time to Wake Up: Epigenetic and Small-RNA-Mediated Regulation during Seed Germination
Lujan, E., & Dinkova, T. D. (2021) · Plants · doi:10.3390/plants10020236 · Cited by 50 · see citing works
“H3K27me3 is deposited by PcG proteins, which form POLYCOMB REPRESSIVE COMPLEX (PRC) 1 and 2 [40].”
BackgroundGjaltema, R. A. F., Schwämmle, T., Kautz, P., Robson, M. I., Schöpflin, R., Lustig, L. R., Brandenburg, L., Dunkel, I., Vechiatto, C., Ntini, E., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.11.023 · Cited by 44 · see citing works
“As nascent transcription can block H3K27me3 deposition (Ho-sogane et al., 2016; Kaneko et al., 2014; Laugesen et al., 2019), transcription might also accelerate removal of the repressive H3K27me3 hotspot, which covers the entire region before differentiation.”
BackgroundPolycomb-dependent histone H2A ubiquitination links developmental disorders with cancer
Tamburri, S., Conway, E., & Pasini, D. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.07.011 · Cited by 50 · see citing works
Wang, J., Wang, J., Yang, L., Zhao, C., Wu, L.-M. N., Xu, L., Zhang, F., Weng, Q., Wegner, M., & Lu, Q. R. (2020) · Nature Communications · doi:10.1038/s41467-020-17955-2 · Cited by 48 · see citing works
Motif-driven interactions between RNA and PRC2 are rheostats that regulate transcription elongation
Rosenberg, M., Blum, R., Kesner, B., Aeby, E., Garant, J., Szántó, A., & Lee, J. T. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-00535-9 · Cited by 49 · see citing works
Histone Modifications in Stem Cell Development and Their Clinical Implications
Völker-Albert, M. C., Bronkhorst, A. J., Holdenrieder, S., & Imhof, A. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.11.002 · Cited by 50 · see citing works
“It appears that recruitment of PRC2 is, similar to Set1A and MLL-containing complexes, likely not (only) based on the recognition of specific sequences but rather on composition-modulated physical properties of DNA, such as the shape of the DNA, nucleosome density, or overall chromatin conformation (Laugesen et al., 2…”
BackgroundEpigenetic Regulation during Primordial Germ Cell Development and Differentiation
Ramakrishna, N. B., Murison, K., Miska, E. A., & Leitch, H. G. (2021) · Sexual Development · doi:10.1159/000520412 · Cited by 47 · see citing works
“Co-regulation by PRC1 and PRC2 complexes is well described [Laugesen et al., 2019]; however, knockout of PRC1 component Rnf2 in mPGCs does not affect H3K27me3 deposition.”
BackgroundEpigenetics as a versatile regulator of fibrosis
Liu, Y., Wen, D., Ho, C., Li, Y., Zheng, D., O’Reilly, S., Gao, Y., Li, Q., & Zhang, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04018-5 · Cited by 48 · see citing works
Persistent epigenetic reprogramming of sweet taste by diet
Vaziri, A., Khabiri, M., Genaw, B. T., May, C. E., Freddolino, P. L., & Dus, M. (2020) · Science Advances · doi:10.1126/sciadv.abc8492 · Cited by 47 · see citing works
“2, which contain distinct accessory factors that influence the targeting of the core complex to the chromatin (18).”
BackgroundInfluentialZheng, Y., Huang, G., Silva, T. C., Yang, Q., Jiang, Y., Koeffler, H. P., Lin, D., & Berman, B. P. (2021) · Nature Communications · doi:10.1038/s41467-021-22720-0 · Cited by 47 · see citing works
Kuo, F.-C., Neville, M. J., Sabaratnam, R., Wesolowska‐Andersen, A., Phillips, D., Wittemans, L. B. L., van Dam, A. D., Loh, N. Y., Todorčević, M., Denton, N., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111136 · Cited by 46 · see citing works
Murphy, S. E., & Boettiger, A. N. (2024) · Nature Genetics · doi:10.1038/s41588-024-01661-6 · Cited by 51 · see citing works
“In the beginning, we defined a block of ~200 monomers to be blue, mimicking the initialization of Polycomb repression by transiently expressed factors during development 5,40 .”
DeLuca, S. Z., Ghildiyal, M., Niu, W., Pang, L.-Y., & Spradling, A. C. (2020) · eLife · doi:10.7554/elife.56922 · Cited by 46 · see citing works
“Nevertheless, many studies have investigated factors controlling PcG targeting specificity in other cell types in both flies and mammals, which offer clues into how PcG is established in early embryos (recently reviewed in Kassis et al., 2017; Kuroda et al., 2020; Laugesen et al., 2019; Yu et al., 2019).”
BackgroundPolycomb Repressive Complex 2 in Eukaryotes—An Evolutionary Perspective
Vijayanathan, M., Trejo-Arellano, M. G., & Mozgová, I. (2022) · Epigenomes · doi:10.3390/epigenomes6010003 · Cited by 43 · see citing works
“CpG islands, hypomethylated CG-rich chromatin regions of 1–2 kb, are associated with PRC2 recruitment in mammals, where accessory subunits rather than transcription factors mediate the recruitment ([180–182], reviewed in the work of [71]).”
BackgroundThe Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development
Loh, C. H., & Veenstra, G. J. C. (2022) · Epigenomes · doi:10.3390/epigenomes6030023 · Cited by 45 · see citing works
“2 complex, is able to bind to H2AK119ub, which is deposited by PRC1.”
BackgroundInfluentialChromatin regulation of transcriptional enhancers and cell fate by the Sotos syndrome gene NSD1
Sun, Z., Lin, Y., Islam, M. T., Koche, R. P., Hedehus, L., Liu, D., Huang, C., Vierbuchen, T., Sawyers, C. L., & Helin, K. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.06.007 · Cited by 44 · see citing works
Shi, Y., Tao, M., Wang, Y., Zang, X., Ma, X., Qiu, A., Zhuang, S., & Liu, N. (2019) · The Journal of Pathology · doi:10.1002/path.5352 · Cited by 45 · see citing works
“Because H3K27me3 tends to form a compact chromatin structure and leads to suppression rather than facilitation of gene expression [49].”
BackgroundChu, L., Qu, Y.-X., An, Y., Hou, L., Li, J., Li, W., Fan, G., Song, B., Li, E., Zhang, L., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04601-6 · Cited by 45 · see citing works
“The core PRC2 complex is composed of three subunits: catalytic subunit EZH2 or EZH1, scaffolding subunit SUZ12 and EED that allosterically activates EZH2 upon binding to H3K27me3 [3, 4].”
BackgroundFang, P., Chen, H., Ma, Z., Han, C., Yin, W., Wang, S., Zhu, H., Xia, W., Wang, J., Xu, L., et al. (2021) · 癌症：英文版 · doi:10.1002/cac2.12181 · Cited by 44 · see citing works
“EZH2, a PRC2 core component, has been reported to epigenetically regulate target gene expression through H3K27me3 histone modification [24].”
BackgroundThe multiscale effects of polycomb mechanisms on 3D chromatin folding
Cheutin, T., & Cavalli, G. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1679082 · Cited by 43 · see citing works
“Much work on PcG proteins targeting to chromatin in mammals focused on deposition of PRC2 and H3K27me3, which is a hallmark of canonical PcG silencing (reviewed in Laugesen et al. 2019).”
BackgroundLoss of PRC2 subunits primes lineage choice during exit of pluripotency
Loh, C. H., van Genesen, S. T., Perino, M., Bark, M. R., & Veenstra, G. J. C. (2021) · Nature Communications · doi:10.1038/s41467-021-27314-4 · Cited by 45 · see citing works
Non-canonical functions of EZH2 in cancer
Zimmerman, S. M., Lin, P. N., & Souroullas, G. P. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1233953 · Cited by 43 · see citing works
“Polycomb-mediated gene silencing primarily operates through the regulation of chromatin structure via posttranslational modifications of histone tails (5, 6).”
BackgroundThe functional mechanisms of mutations in myelodysplastic syndrome
Nagata, Y., & Maciejewski, J. P. (2019) · Leukemia · doi:10.1038/s41375-019-0617-3 · Cited by 42 · see citing works
Chomiak, A. A., Tiedemann, R. L., Liu, Y., Kong, X., Cui, Y., Wiseman, A. K., Thurlow, K. E., Cornett, E. M., Topper, M. J., Baylin, S. B., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk4423 · Cited by 42 · see citing works
Williams, K. B., & Largaespada, D. A. (2020) · Genes · doi:10.3390/genes11050477 · Cited by 42 · see citing works
“JARID2 is a critical component of the PCR2 complex required for localization of the PRC2 complex on chromatin, and has been reviewed before [45].”
BackgroundWang, J., Yang, L., Dong, C., Wang, J., Xu, L., Qiu, Y., Weng, Q., Zhao, C., Xin, M., & Lu, Q. R. (2020) · Science Advances · doi:10.1126/sciadv.aaz6477 · Cited by 42 · see citing works
“Since PRC2 activity regulates H3K27me3 levels (6), we examined the H3K27me3 state during OPC maturation.”
BackgroundInfluentialXu, J., Zhao, X., Mao, F., Basrur, V., Ueberheide, B. M., Chait, B. T., Allis, C. D., Taverna, S. D., Gao, S., Wang, W., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1262 · Cited by 42 · see citing works
“While these results implicate long ncRNA and sRNA in Polycomb repression, mechanistic details concerning their role in the recruitment of PcG proteins are still largely missing, and they may differ between species (30– 32).”
Zhang, Q., Agius, S. C., Flanigan, S. F., Uckelmann, M., Levina, V., Owen, B. M., & Davidovich, C. (2021) · Nature Communications · doi:10.1038/s41467-021-24866-3 · Cited by 42 · see citing works
- Authors
- Laugesen, A., Højfeldt, J. W., & Helin, K.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Helin, Kristian
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 74
- Issue
- 1
- Pages
- 8-18
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6452890
- OpenAlex
- W2925415367
- Cited by
- 602
- References
- 105
- Citations by year
- 2026: 60 · 2025: 89 · 2024: 85 · 2023: 83 · 2022: 79 · 2021: 87 · 2020: 83 · 2019: 36
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Danmarks Grundforskningsfond (DNRF 82)
- Novo Nordisk Fonden (NNF16OC0023234)
- National Cancer Institute (P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- polycomb repressive complex 2, H3K27 methylation, histone methyltransferase, gene silencing, cancer therapy targets
- MeSH terms
- Animals, Histones, Humans, Lysine, Methylation, Protein Binding, DNA Methylation, Chromatin Assembly and Disassembly, Polycomb Repressive Complex 2
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