polycomb repressive complex 2

Summary

Summary: A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.

Top Publications

  1. Tuma R. Epigenetic therapies move into new territory, but how exactly do they work?. J Natl Cancer Inst. 2009;101:1300-1 pubmed publisher
  2. Ardehali M, Anselmo A, Cochrane J, Kundu S, Sadreyev R, Kingston R. Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription. Mol Cell. 2017;68:872-884.e6 pubmed publisher
    b>Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development...
  3. Wang X, Goodrich K, Gooding A, Naeem H, Archer S, Paucek R, et al. Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. Mol Cell. 2017;65:1056-1067.e5 pubmed publisher
    b>Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo...
  4. Mohammad F, Weissmann S, Leblanc B, Pandey D, Højfeldt J, Comet I, et al. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nat Med. 2017;23:483-492 pubmed publisher
    ..H3K27M has been shown to inhibit polycomb repressive complex 2 (PRC2), a multiprotein complex responsible for the methylation of H3 at lysine 27 (H3K27me), by ..
  5. Campbell R, Tummino P. Cancer epigenetics drug discovery and development: the challenge of hitting the mark. J Clin Invest. 2014;124:64-9 pubmed publisher
    ..We will also highlight recent successes in cancer epigenetics drug discovery and consider important factors for clinical success in this burgeoning area. ..
  6. Klose R, Cooper S, Farcas A, Blackledge N, Brockdorff N. Chromatin sampling--an emerging perspective on targeting polycomb repressor proteins. PLoS Genet. 2013;9:e1003717 pubmed publisher
  7. Nakagawa R, Leyland R, Meyer Hermann M, Lu D, Turner M, Arbore G, et al. MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis. J Clin Invest. 2016;126:377-88 pubmed publisher
    ..Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes. ..
  8. Kedage V, Strittmatter B, Dausinas P, Hollenhorst P. Phosphorylation of the oncogenic transcription factor ERG in prostate cells dissociates polycomb repressive complex 2, allowing target gene activation. J Biol Chem. 2017;292:17225-17235 pubmed publisher
    ..We found that the Ser-96 phosphorylation resulted in dissociation of EZH2 and SUZ12, components of polycomb repressive complex 2 (PRC2), transcriptional activation of ERG target genes, and increased cell migration...
  9. Tsubota S, Kishida S, Shimamura T, Ohira M, Yamashita S, Cao D, et al. PRC2-Mediated Transcriptomic Alterations at the Embryonic Stage Govern Tumorigenesis and Clinical Outcome in MYCN-Driven Neuroblastoma. Cancer Res. 2017;77:5259-5271 pubmed publisher
    ..Together, our findings highlighted PRC2-mediated transcriptional control during embryogenesis as a critical step in the development and clinical outcome of neuroblastoma. Cancer Res; 77(19); 5259-71. ©2017 AACR. ..

More Information

Publications45

  1. Clancy K, Russell A, Subramanian V, Nguyen H, Qian Y, Campbell R, et al. Citrullination/Methylation Crosstalk on Histone H3 Regulates ER-Target Gene Transcription. ACS Chem Biol. 2017;12:1691-1702 pubmed publisher
    ..In total, our studies support the existence of crosstalk between citrullination of H3R26 and methylation of H3K27. ..
  2. Vogt J, Bengesser K, Claes K, Wimmer K, Mautner V, van Minkelen R, et al. SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints. Genome Biol. 2014;15:R80 pubmed publisher
  3. Morgan M, Shilatifard A. Medicine. (Poly)combing the pediatric cancer genome for answers. Science. 2013;340:823-4 pubmed publisher
  4. Bratkowski M, Yang X, Liu X. Polycomb repressive complex 2 in an autoinhibited state. J Biol Chem. 2017;292:13323-13332 pubmed publisher
    ..b>Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (..
  5. Yu W, Zhang F, Wang S, Fu Y, Chen J, Liang X, et al. Depletion of polycomb repressive complex 2 core component EED impairs fetal hematopoiesis. Cell Death Dis. 2017;8:e2744 pubmed publisher
    b>Polycomb repressive complex 2 (PRC2), a H3K27me3 methyltransferase complex, promotes the development of many organs by silencing ectopic transcription program...
  6. Fornaro L, Crea F, Masi G, Paolicchi E, Loupakis F, Graziano F, et al. EZH2 polymorphism and benefit from bevacizumab in colorectal cancer: another piece to the puzzle. Ann Oncol. 2012;23:1370-1 pubmed publisher
  7. Xu M, Zuo D, Liu X, Fan H, Chen Q, Deng S, et al. MiR-155 contributes to Th17 cells differentiation in dextran sulfate sodium (DSS)-induced colitis mice via Jarid2. Biochem Biophys Res Commun. 2017;488:6-14 pubmed publisher
    ..This study suggests that miR-155 plays a host-damaging role during DSS-induced colitis mice and induces Th17 differentiation by targeting Jarid2. ..
  8. Holoch D, Margueron R. Mechanisms Regulating PRC2 Recruitment and Enzymatic Activity. Trends Biochem Sci. 2017;42:531-542 pubmed publisher
    b>Polycomb repressive complex 2 (PRC2) and its histone H3 lysine-27 methylation activity are crucial for multicellular development by virtue of their role in maintaining transcriptional repression patterns...
  9. Bradley W, Arora S, Busby J, Balasubramanian S, Gehling V, Nasveschuk C, et al. EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation. Chem Biol. 2014;21:1463-75 pubmed publisher
    ..Importantly, we find that these inhibitors are broadly efficacious also in NHL models with wild-type EZH2. ..
  10. Gnad F, Doll S, Manning G, Arnott D, Zhang Z. Bioinformatics analysis of thousands of TCGA tumors to determine the involvement of epigenetic regulators in human cancer. BMC Genomics. 2015;16 Suppl 8:S5 pubmed publisher
    ..Our predictor uncovered one OG and several TSGs among ERGs. Expression analyses elucidated multiple dysregulated ERGs including EZH2 as member of a co-expressed cell cycle network. ..
  11. Ai S, Yu X, Li Y, Peng Y, Li C, Yue Y, et al. Divergent Requirements for EZH1 in Heart Development Versus Regeneration. Circ Res. 2017;121:106-112 pubmed publisher
    b>Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes...
  12. Prokopuk L, Stringer J, Hogg K, Elgass K, Western P. PRC2 is required for extensive reorganization of H3K27me3 during epigenetic reprogramming in mouse fetal germ cells. Epigenetics Chromatin. 2017;10:7 pubmed publisher
    ..Here, we show that Polycomb Repressive Complex 2 is transiently localized in the nucleus of mouse fetal germ cells, while DNA methylation is removed ..
  13. Gray S, Amezquita R, Guan T, Kleinstein S, Kaech S. Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8+ T Cell Terminal Differentiation and Loss of Multipotency. Immunity. 2017;46:596-608 pubmed publisher
    ..b>Polycomb repressive complex 2 deficiency impaired clonal expansion and TE cell differentiation, but minimally impacted CD8+
  14. Shiekhattar R. PINTing for p53. Genome Biol. 2013;14:132 pubmed
    ..A new study identifies the long noncoding RNA Pintas a regulator of cellular proliferation and a target of the p53 pathway. ..
  15. Zhang J, Wu W, Xu S, Zhang J, Zhang J, Yu Q, et al. MicroRNA-105 inhibits human glioma cell malignancy by directly targeting SUZ12. Tumour Biol. 2017;39:1010428317705766 pubmed publisher
    ..Taken together, our results indicate that miR-105 plays a significant role in tumor behavior and malignant progression, which may provide a novel therapeutic strategy for the treatment of glioma and other cancers. ..
  16. Parvani J, Schiemann W. Sox4, EMT programs, and the metastatic progression of breast cancers: mastering the masters of EMT. Breast Cancer Res. 2013;15:R72 pubmed
    ..This viewpoint highlights Sox4 as a 'new' master of EMT programs and metastatic breast cancer. ..
  17. Grossmann V, Bacher U, Kohlmann A, Artusi V, Klein H, Dugas M, et al. EZH2 mutations and their association with PICALM-MLLT10 positive acute leukaemia. Br J Haematol. 2012;157:387-90 pubmed publisher
  18. Wang W, Xiao X, Chen X, Huo Y, Xi W, Lin Z, et al. Tumor-suppressive miR-145 co-repressed by TCF4-β-catenin and PRC2 complexes forms double-negative regulation loops with its negative regulators in colorectal cancer. Int J Cancer. 2018;142:308-321 pubmed publisher
    ..Collectively, we elucidated the detailed molecular mechanism of how dysregulated Wnt/β-catenin signaling and tumor-suppressive miRNAs reciprocally regulate each other in CRC cells. ..
  19. Wang A, Juan A, Ko K, Tsai P, Zare H, Dell Orso S, et al. The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins. Mol Cell. 2017;68:398-413.e6 pubmed publisher
    ..Thus, in addition to serving as a histone chaperone and transcription elongation factor, Spt6 counteracts repression by opposing H3K27me3 deposition at critical genomic regulatory regions. ..
  20. Bodor C, O Riain C, Wrench D, Matthews J, Iyengar S, Tayyib H, et al. EZH2 Y641 mutations in follicular lymphoma. Leukemia. 2011;25:726-9 pubmed publisher
  21. Vo B, Li C, Morgan M, Theurillat I, Finkelstein D, Wright S, et al. Inactivation of Ezh2 Upregulates Gfi1 and Drives Aggressive Myc-Driven Group 3 Medulloblastoma. Cell Rep. 2017;18:2907-2917 pubmed publisher
    ..Although negative regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects. ..
  22. Wagner T, Jung M. New lysine methyltransferase drug targets in cancer. Nat Biotechnol. 2012;30:622-3 pubmed publisher
  23. Liu S, Chen D, Shen W, Chen L, Yu A, Fu H, et al. EZH2 Mediates the Regulation of S100A4 on E-cadherin Expression and the Proliferation, Migration of Gastric Cancer Cells. Hepatogastroenterology. 2015;62:737-41 pubmed
    ..As a novel downstream target of S100A4, EZH2 mediates the inhibition of S100A4 on E-cadherin. The SET domain is important for EZH2 in mediating the cellular function of S100A4. ..
  24. Ciarapica R, Russo G, Verginelli F, Raimondi L, Donfrancesco A, Rota R, et al. Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. Cell Cycle. 2009;8:172-5 pubmed
  25. Xie L, Zhang Z, Tan Z, He R, Zeng X, Xie Y, et al. MicroRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer. Mol Cell Biochem. 2014;392:153-9 pubmed
    ..Therefore, miR-124 shows tumor-suppressive activity and may be a new and useful approach of gastric cancer therapy. ..
  26. Neri F, Incarnato D, Krepelova A, Rapelli S, Pagnani A, Zecchina R, et al. Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells. Genome Biol. 2013;14:R91 pubmed publisher
    ..We find that 5hmC co-localization with Polycomb repressive complex 2 (PRC2) is specific to ESCs and is absent in differentiated cells...
  27. Eun S, Feng L, Cedeno Rosario L, Gan Q, Wei G, Cui K, et al. Polycomb Group Gene E(z) Is Required for Spermatogonial Dedifferentiation in Drosophila Adult Testis. J Mol Biol. 2017;429:2030-2041 pubmed publisher
    ..Taken together, our data suggest that E(z) acts intrinsically in germ cells to activate dedifferentiation and thus replenish lost GSCs during both aging and tissue regeneration. ..
  28. Gherardi S, Ripoche D, Mikaelian I, Chanal M, Teinturier R, Goehrig D, et al. Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification. Biochim Biophys Acta Gene Regul Mech. 2017;1860:427-437 pubmed publisher
    ..Our data suggests therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. ..
  29. Kikuchi J, Koyama D, Wada T, Izumi T, Hofgaard P, Bogen B, et al. Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma. J Clin Invest. 2015;125:4375-90 pubmed publisher
  30. Barsotti A, Ryskin M, Rollins R. Epigenetic reprogramming in solid tumors: therapeutic implications of EZH2 gain-of-function mutations. Epigenomics. 2015;7:687-90 pubmed publisher
  31. Shen W, Clemente M, Hosono N, Yoshida K, Przychodzen B, Yoshizato T, et al. Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria. J Clin Invest. 2014;124:4529-38 pubmed publisher
    ..Together, our data indicate that in addition to PIGA mutations, accessory genetic events are frequent in PNH, suggesting a stepwise clonal evolution derived from a singular stem cell clone. ..
  32. Abdel Wahab O, Pardanani A, Patel J, Wadleigh M, Lasho T, Heguy A, et al. Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia. 2011;25:1200-2 pubmed publisher
  33. Xiao J, Jin R, Yu X, Shen M, Wagner J, Pai A, et al. Cis and trans determinants of epigenetic silencing by Polycomb repressive complex 2 in Arabidopsis. Nat Genet. 2017;49:1546-1552 pubmed publisher
    ..Here we define short genomic fragments, known as Polycomb response elements (PREs), that direct Polycomb repressive complex 2 (PRC2) placement at developmental genes regulated by silencing in Arabidopsis thaliana...
  34. Grossmann V, Kohlmann A, Eder C, Haferlach C, Kern W, Cross N, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia. 2011;25:877-9 pubmed publisher
  35. Nishioka K, Wang X, Miyazaki H, Soejima H, Hirose S. Mbf1 ensures Polycomb silencing by protecting E(z) mRNA from degradation by Pacman. Development. 2018;145: pubmed publisher
    ..i>In vitro, Mbf1 protected E(z) RNA from Pcm activity. Our results suggest that Mbf1 buffers fluctuations in Pcm activity to maintain an E(z) mRNA expression level sufficient for Polycomb silencing. ..
  36. Simon J. Stopping a chromatin enzyme. Nat Chem Biol. 2012;8:875-6 pubmed publisher