Schuettengruber, B., Bourbon, H. M., Di Croce, L. & Cavalli, G. Genome regulation by polycomb and trithorax: 70 years and counting. Cell 171, 34–57 (2017).
Margueron, R. & Reinberg, D. The polycomb complex PRC2 and its mark in life. Nature 469, 343–349 (2011).
Simon, J. A. & Kingston, R. E. Occupying chromatin: polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol. Cell 49, 808–824 (2013).
Comet, I., Riising, E. M., Leblanc, B. & Helin, K. Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. Nat. Rev. Cancer 16, 803–810 (2016).
Kasinath, V. et al. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science 359, 940–944 (2018).
Chen, S., Jiao, L., Shubbar, M., Yang, X. & Liu, X. Unique structural platforms of Suz12 dictate distinct classes of PRC2 for chromatin binding. Mol. Cell 69, 840–852 e5 (2018).
Ciferri, C. et al. Molecular architecture of human polycomb repressive complex 2. eLife 1, e00005 (2012).
Margueron, R. et al. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461, 762–767 (2009).
Jiao, L. & Liu, X. Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2. Science 350, aac4383 (2015).
Justin, N. et al. Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat. Commun. 7, 11316 (2016).
Sanulli, S. et al. Jarid2 Methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation. Mol. Cell 57, 769–783 (2015).
Lee, C. H. et al. Allosteric activation dictates PRC2 activity independent of its recruitment to chromatin. Mol. Cell 70, 422–434 (2018).
Perino, M. et al. MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding. Nat. Genet. 50, 1002–1010 (2018).
Lee, C. H. et al. Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2. Mol. Cell 70, 435–448 (2018).
Wang, X. et al. Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA. Nat. Struct. Mol. Biol. 24, 1028–1038 (2017).
Li, H. et al. Polycomb-like proteins link the PRC2 complex to CpG islands. Nature 549, 287–291 (2017).
Choi, J. et al. DNA binding by PHF1 prolongs PRC2 residence time on chromatin and thereby promotes H3K27 methylation. Nat. Struct. Mol. Biol. 24, 1039–1047 (2017).
Beringer, M. et al. EPOP functionally links elongin and polycomb in pluripotent stem cells. Mol. Cell 64, 645–658 (2016).
Zhang, Z. et al. PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming. Stem Cells 29, 229–240 (2011).
Kloet, S. L. et al. The dynamic interactome and genomic targets of polycomb complexes during stem-cell differentiation. Nat. Struct. Mol. Biol. 23, 682–690 (2016).
Hauri, S. et al. A high-density map for navigating the human polycomb complexome. Cell Rep. 17, 583–595 (2016).
Smits, A. H., Jansen, P. W., Poser, I., Hyman, A. A. & Vermeulen, M. Stoichiometry of chromatin-associated protein complexes revealed by label-free quantitative mass spectrometry-based proteomics. Nucleic Acids Res. 41, e28 (2013).
Brockdorff, N. Noncoding RNA and polycomb recruitment. RNA 19, 429–442 (2013).
Davidovich, C. & Cech, T. R. The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2. RNA 21, 2007–2022 (2015).
Hekimoglu, B. & Ringrose, L. Non-coding RNAs in polycomb/trithorax regulation. RNA Biol. 6, 129–137 (2009).
Ringrose, L. Noncoding RNAs in polycomb and trithorax regulation: a quantitative perspective. Annu. Rev. Genet. 51, 385–411 (2017).
Bonasio, R. & Shiekhattar, R. Regulation of transcription by long noncoding RNAs. Annu. Rev. Genet. 48, 433–455 (2014).
Kaneko, S., Son, J., Bonasio, R., Shen, S. S. & Reinberg, D. Nascent RNA interaction keeps PRC2 activity poised and in check. Genes Dev. 28, 1983–1988 (2014).
Herzog, V. A. et al. A strand-specific switch in noncoding transcription switches the function of a polycomb/trithorax response element. Nat. Genet. 46, 973–981 (2014).
Cifuentes-Rojas, C., Hernandez, A. J., Sarma, K. & Lee, J. T. Regulatory interactions between RNA and polycomb repressive complex 2. Mol. Cell 55, 171–185 (2014).
Zhao, J., Sun, B. K., Erwin, J. A., Song, J. J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750–756 (2008).
Kaneko, S. et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev. 24, 2615–2620 (2010).
Kanhere, A. et al. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol. Cell 38, 675–688 (2010).
Wang, X. et al. Targeting of Polycomb Repressive Complex 2 to RNA by short repeats of consecutive guanines. Mol. Cell 65, 1056–1067 e5 (2017).
Long, Y. et al. Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2. eLlife 6, e31558 (2017).
Beltran, M. et al. The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res. 26, 896–907 (2016).
Ardehali, M. B. et al. Polycomb Repressive Complex 2 methylates elongin a to regulate transcription. Mol. Cell 68, 872–884 e6 (2017).
He, C. et al. High-resolution mapping of RNA-binding regions in the nuclear proteome of embryonic stem cells. Mol. Cell 64, 416–430 (2016).
Davidovich, C., Zheng, L., Goodrich, K. J. & Cech, T. R. Promiscuous RNA binding by Polycomb Repressive Complex 2. Nat. Struct. Mol. Biol. 20, 1250–1257 (2013).
Kaneko, S. et al. Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol. Cell 53, 290–300 (2014).
Montero, J. J. et al. TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin. Nat. Commun. 9, 1548 (2018).
Castello, A. et al. Comprehensive Identification of RNA-binding domains in human cells. Mol. Cell 63, 696–710 (2016).
He, Y. et al. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat. Chem. Biol. 13, 389–395 (2017).
Ballare, C. et al. Phf19 links methylated Lys36 histone H3 to regulation polycomb activity. Nat. Struct. Mol. Biol. 19, 1257–1265 (2012).
Conway, E. et al. A family vertebrate-specific polycombs encoded by the LCOR/LCORL genes balance PRC2 subtype activities. Mol. Cell 70, 408–421 e8 (2018).
Oksuz, O. et al. Capturing the onset PRC2-mediated repressive domain formation. Mol. Cell 70, 1149–1162 e5 (2018).
Poepsel, S., Kasinath, V. & Nogales, E. Cryo-EM structures PRC2 simultaneously engaged with two functionally distinct nucleosomes. Nat. Struct. Mol. Biol. 25, 154–162 (2018).
Lee, C. H., Granat, J., Yu, J.-R., LeRoy, G. Stafford, J. & Reinberg, D. Automethylation of PRC2 fine-tunes its catalytic activity on chromatin. Preprint at bioRxiv https://doi.org/10.1101/349449 (2018).
Wang, X., Long, Y., Paucek, R. D., Gooding, A. R., Lee, T. & Cech, T. R. Regulation of histone methylation by automethylation of PRC2. Preprint at bioRxiv https://doi.org/10.1101/343020 (2018).
Warneford-Thomson, R., He, C., Sidoli, S., Garcia, B. A. & Bonasio, R. Sample preparation for mass spectrometry-based identification of RNA-binding regions. J. Vis. Exp. 127, https://doi.org/10.3791/56004 (2017).
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).
Davidovich, C., Goodrich, K. J., Gooding, A. R. & Cech, T. R. A dimeric state for PRC2. Nucleic Acids Res. 42, 9236–9248 (2014).
Yang, B. et al. Identification of cross-linked peptides from complex samples. Nat. Methods 9, 904–906 (2012).
Combe, C. W., Fischer, L. & Rappsilber, J. xiNET: cross-link network maps with residue resolution. Mol. Cell. Proteomics 14, 1137–1147 (2015).
Luger, K., Rechsteiner, T. J. & Richmond, T. J. Preparation of nucleosome core particle from recombinant histones. Methods Enzymol. 304, 3–19 (1999).
Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671–675 (2012).
Kaneko, S., Son, J., Shen, S. S., Reinberg, D. & Bonasio, R. PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nat. Struct. Mol. Biol. 20, 1258–1264 (2013).