Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation

Brown, 1966, Heterochromatin, Science, 151, 417, 10.1126/science.151.3709.417

Larson, 2018, The role of phase separation in heterochromatin formation, function, and regulation, Biochemistry, 57, 2540, 10.1021/acs.biochem.8b00401

Trojer, 2007, Facultative heterochromatin: is there a distinctive molecular signature?, Mol. Cell, 28, 1, 10.1016/j.molcel.2007.09.011

Reinberg, 2018, Chromatin domains rich in inheritance, Science, 361, 33, 10.1126/science.aat7871

Allshire, 2018, Ten principles of heterochromatin formation and function, Nat. Rev. Mol. Cell Biol, 19, 229, 10.1038/nrm.2017.119

Heard, 2005, Delving into the diversity of facultative heterochromatin: the epigenetics of the inactive X chromosome, Curr. Opin. Genet. Dev, 15, 482, 10.1016/j.gde.2005.08.009

Schuettengruber, 2017, Genome regulation by Polycomb and Trithorax: 70 years and counting, Cell, 171, 34, 10.1016/j.cell.2017.08.002

Cao, 2002, Role of histone H3 lysine 27 methylation in Polycomb-group silencing, Science, 298, 1039, 10.1126/science.1076997

Czermin, 2002, Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites, Cell, 111, 185, 10.1016/S0092-8674(02)00975-3

Kuzmichev, 2002, Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein, Genes Dev, 16, 2893, 10.1101/gad.1035902

Müller, 2002, Histone methyltransferase activity of a Drosophila Polycomb group repressor complex, Cell, 111, 197, 10.1016/S0092-8674(02)00976-5

Shen, 2008, EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency, Mol. Cell, 32, 491, 10.1016/j.molcel.2008.10.016

Margueron, 2009, Role of the polycomb protein EED in the propagation of repressive histone marks, Nature, 461, 762, 10.1038/nature08398

Xu, 2010, Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2), Proc. Natl. Acad. Sci. U.S.A, 107, 19266, 10.1073/pnas.1008937107

Zhen, 2016, Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets polycomb Cbx7-PRC1 to chromatin, Elife, 5, e17667, 10.7554/eLife.17667

Wang, 2004, Role of histone H2A ubiquitination in Polycomb silencing, Nature, 431, 873, 10.1038/nature02985

de Napoles, 2004, Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation, Dev. Cell, 7, 663, 10.1016/j.devcel.2004.10.005

Kalb, 2014, Histone H2A monoubiquitination promotes histone H3 methylation in Polycomb repression, Nat. Struct. Mol. Biol, 21, 569, 10.1038/nsmb.2833

Blackledge, 2014, Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation, Cell, 157, 1445, 10.1016/j.cell.2014.05.004

Grau, 2011, Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge, Genes Dev, 25, 2210, 10.1101/gad.17288211

Lau, 2017, Mutation of a nucleosome compaction region disrupts Polycomb-mediated axial patterning, Science, 355, 1081, 10.1126/science.aah5403

King, 2005, Analysis of a polycomb group protein defines regions that link repressive activity on nucleosomal templates to in vivo function, Mol. Cell. Biol, 25, 6578, 10.1128/MCB.25.15.6578-6591.2005

Francis, 2004, Chromatin compaction by a polycomb group protein complex, Science, 306, 1574, 10.1126/science.1100576

Pirrotta, 2012, A view of nuclear Polycomb bodies, Curr. Opin. Genet. Dev, 22, 101, 10.1016/j.gde.2011.11.004

Isono, 2013, SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing, Dev Cell, 26, 565, 10.1016/j.devcel.2013.08.016

Kondo, 2014, Polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue-specific enhancer, Dev. Cell, 28, 94, 10.1016/j.devcel.2013.11.021

Kundu, 2017, Polycomb repressive complex 1 generates discrete compacted domains that change during differentiation, Mol. Cell, 65, 432, 10.1016/j.molcel.2017.01.009

Wani, 2016, Chromatin topology is coupled to Polycomb group protein subnuclear organization, Nat. Commun, 7, 10291, 10.1038/ncomms10291

Shin, 2017, Liquid phase condensation in cell physiology and disease, Science, 357, eaaf4382, 10.1126/science.aaf4382

Banani, 2017, Biomolecular condensates: organizers of cellular biochemistry, Nat. Rev. Mol. Cell Biol, 18, 285, 10.1038/nrm.2017.7

Hyman, 2014, Liquid-liquid phase separation in biology, Annu. Rev. Cell Dev. Biol, 30, 39, 10.1146/annurev-cellbio-100913-013325

Boeynaems, 2018, Protein phase separation: a new phase in cell biology, Trends Cell Biol, 28, 420, 10.1016/j.tcb.2018.02.004

Woodruff, 2018, Organization and function of non-dynamic biomolecular condensates, Trends Biochem. Sci, 43, 81, 10.1016/j.tibs.2017.11.005

Meldi, 2011, Compartmentalization of the nucleus, Trends Cell Biol, 21, 701, 10.1016/j.tcb.2011.08.001

Cho, 2018, Mediator and RNA polymerase II clusters associate in transcription-dependent condensates, Science, 361, 412, 10.1126/science.aar4199

Chong, 2018, Imaging dynamic and selective low-complexity domain interactions that control gene transcription, Science, 361, eaar2555, 10.1126/science.aar2555

Sabari, 2018, Coactivator condensation at super-enhancers links phase separation and gene control, Science, 361, eaar3958, 10.1126/science.aar3958

Boehning, 2018, RNA polymerase II clustering through carboxy-terminal domain phase separation, Nat. Struct. Mol. Biol, 25, 833, 10.1038/s41594-018-0112-y

Lu, 2018, Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II, Nature, 558, 318, 10.1038/s41586-018-0174-3

Strom, 2017, Phase separation drives heterochromatin domain formation, Nature, 547, 241, 10.1038/nature22989

Larson, 2017, Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin, Nature, 547, 236, 10.1038/nature22822

Ren, 2008, Changes in the distributions and dynamics of polycomb repressive complexes during embryonic stem cell differentiation, Mol. Cell. Biol, 28, 2884, 10.1128/MCB.00949-07

Alkema, 1997, Identification of Bmi1-interacting proteins as constituents of a multimeric mammalian Polycomb complex, Gene Dev, 11, 226, 10.1101/gad.11.2.226

Schoorlemmer, 1997, Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain, EMBO J, 16, 5930, 10.1093/emboj/16.19.5930

Tatavosian, 2015, Distinct cellular assembly stoichiometry of Polycomb complexes on chromatin revealed by single-molecule chromatin immunoprecipitation imaging, J. Biol. Chem, 290, 28038, 10.1074/jbc.M115.671115

Levine, 2002, The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans, Mol. Cell. Biol, 22, 6070, 10.1128/MCB.22.17.6070-6078.2002

Satijn, 1997, RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor, Mol. Cell. Biol, 17, 4105, 10.1128/MCB.17.7.4105

Gunster, 1997, Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic, Mol. Cell. Biol, 17, 2326, 10.1128/MCB.17.4.2326

Zhen, 2014, Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes, Mol. Biol. Cell, 25, 3726, 10.1091/mbc.e14-06-1109

Piovesan, 2018, MobiDB 3.0: more annotations for intrinsic disorder, conformational diversity and interactions in proteins, Nucleic Acids Res, 46, D471, 10.1093/nar/gkx1071

Kawaguchi, 2017, Phosphorylation of CBX2 controls its nucleosome-binding specificity, J. Biochem, 162, 343, 10.1093/jb/mvx040

Wang, 2018, A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins, Cell, 174, 688, 10.1016/j.cell.2018.06.006

Boeynaems, 2017, Phase separation of C9orf72 dipeptide repeats perturbs stress granule dynamics, Mol. Cell, 65, 1044, 10.1016/j.molcel.2017.02.013

Lee, 2016, C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles, Cell, 167, 774, 10.1016/j.cell.2016.10.002

Jiang, 2015, Phase transition of spindle-associated protein regulate spindle apparatus assembly, Cell, 163, 108, 10.1016/j.cell.2015.08.010

Nott, 2015, Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles, Mol. Cell, 57, 936, 10.1016/j.molcel.2015.01.013

Pak, 2016, Sequence determinants of intracellular phase separation by complex coacervation of a disordered protein, Mol. Cell, 63, 72, 10.1016/j.molcel.2016.05.042

Mitrea, 2018, Self-interaction of NPM1 modulates multiple mechanisms of liquid-liquid phase separation, Nat. Commun, 9, 842, 10.1038/s41467-018-03255-3

Feric, 2016, Coexisting liquid phases underlie nucleolar subcompartments, Cell, 165, 1686, 10.1016/j.cell.2016.04.047

Elbaum-Garfinkle, 2015, The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics, Proc. Natl. Acad. Sci. U.S.A, 112, 7189, 10.1073/pnas.1504822112

Patel, 2015, A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation, Cell, 162, 1066, 10.1016/j.cell.2015.07.047

Altmeyer, 2015, Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose), Nat. Commun, 6, 8088, 10.1038/ncomms9088

Senthilkumar, 2009, Novel motifs distinguish multiple homologues of Polycomb in vertebrates: expansion and diversification of the epigenetic toolkit, BMC Genomics, 10, 549, 10.1186/1471-2164-10-549

Blackledge, 2015, Targeting Polycomb systems to regulate gene expression: modifications to a complex story, Nat. Rev. Mol. Cell Biol, 16, 643, 10.1038/nrm4067

Kaustov, 2011, Recognition and specificity determinants of the human Cbx chromodomains, J. Biol. Chem, 286, 521, 10.1074/jbc.M110.191411

Bernstein, 2006, Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin, Mol. Cell. Biol, 26, 2560, 10.1128/MCB.26.7.2560-2569.2006

Semenov, 1998, Thermoreversible gelation in solutions of associative polymers. 1. Statics, Macromolecules, 31, 1373, 10.1021/ma970616h

Banani, 2016, Compositional control of phase-separated cellular bodies, Cell, 166, 651, 10.1016/j.cell.2016.06.010

Hemenway, 1998, The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING finger domains, Oncogene, 16, 2541, 10.1038/sj.onc.1202042

Satijn, 1999, RING1 interacts with multiple Polycomb-group proteins and displays tumorigenic activity, Mol. Cell. Biol, 19, 57, 10.1128/MCB.19.1.57

Wang, 2008, Structural transitions of the RING1B C-terminal region upon binding the polycomb cbox domain, Biochemistry, 47, 8007, 10.1021/bi800857f

Wang, 2010, Polycomb group targeting through different binding partners of RING1B C-terminal domain, Structure, 18, 966, 10.1016/j.str.2010.04.013

Tardat, 2015, Cbx2 targets PRC1 to constitutive heterochromatin in mouse zygotes in a parent-of-origin-dependent manner, Mol. Cell, 58, 157, 10.1016/j.molcel.2015.02.013

Kim, 2002, The SAM domain of polyhomeotic forms a helical polymer, Nat. Struct. Biol, 9, 453

Kim, 2003, SAM domains: uniform structure, diversity of function, Trends Biochem. Sci, 28, 625, 10.1016/j.tibs.2003.11.001

Eskeland, 2010, Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination, Mol. Cell, 38, 452, 10.1016/j.molcel.2010.02.032

Schoenfelder, 2015, Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome, Nat. Genet, 47, 1179, 10.1038/ng.3393

Penny, 1996, Requirement for Xist in X chromosome inactivation, Nature, 379, 131, 10.1038/379131a0

Katoh-Fukui, 1998, Male-to-female sex reversal in M33 mutant mice, Nature, 393, 688, 10.1038/31482

Endoh, 2008, Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity, Development, 135, 1513, 10.1242/dev.014340

Huynh, 2017, Producing GST-Cbx7 fusion proteins from Escherichia coli, Bio Protoc, 7, e2333, 10.21769/BioProtoc.2333

Duc, 2017, Labelling HaloTag fusion proteins with HaloTag ligand in living cells, Bio Protoc, 7, e2526, 10.21769/BioProtoc.2526