2,478
Views
32
CrossRef citations to date
0
Altmetric
Review

Role of EZH2 histone methyltrasferase in melanoma progression and metastasis

, , , , &
Pages 579-591 | Received 04 Sep 2015, Accepted 13 Mar 2016, Published online: 17 Jun 2016

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016 Jan; 66(1):7-30; PMID:26742998; http://dx.doi.org/10.3322/caac.21332
  • Atrash S, Makhoul I, Mizell JS, Hutchins L, Mahmoud F. Response of metastatic mucosal melanoma to immunotherapy: It can get worse before it gets better. J Oncol Pharm Pract 2016 Jan 24; PMID:26811403
  • Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Sep 24; 373(13):1270-1; PMID:26398076; http://dx.doi.org/10.1056/NEJMc1509660
  • Buchbinder EI, Hodi FS. Melanoma in 2015: Immune-checkpoint blockade - durable cancer control. Nat Rev Clin Oncol 2016 Feb; 13(2):77-8; PMID:26787285; http://dx.doi.org/10.1038/nrclinonc.2015.237
  • Berger SL. The complex language of chromatin regulation during transcription. Nature 2007 May 24; 447(7143):407-12; PMID:17522673; http://dx.doi.org/10.1038/nature05915
  • Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004 Feb; 4(2):143-53; PMID:14732866; http://dx.doi.org/10.1038/nrc1279
  • Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature 2011 Jan 20; 469(7330):343-9; PMID:21248841; http://dx.doi.org/10.1038/nature09784
  • Verma SK, Tian X, LaFrance LV, Duquennet C, Suarez DP, Newlander KA, Romeril SP, Burgess JL, Grant SW, Brackley JA, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2; ACS Med Chem Lett. 2012 Oct 19; 3(12):1091-6; doi: 10.1021/ml3003346. eCollection 2012.
  • Marchesi Irene BL. Role of Enhancer of Zeste Homolog 2 Polycomb Protein and Its Significance in Tumor Progression and Cell Differentiation. In: Danuta Radzioch, editor. Chromatin Remodelling Intech; 2013.
  • Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA, Salvesen HB, Otte AP, Akslen LA. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 2006 Jan 10; 24(2):268-73; PMID:16330673; http://dx.doi.org/10.1200/JCO.2005.01.5180
  • Chen H, Tu SW, Hsieh JT. Downregulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J Biol Chem 2005 Jun 10; 280(23):22437-44; PMID:15817459; http://dx.doi.org/10.1074/jbc.M501379200
  • Avaritt NF, Mahmoud F, Sengupta D, Makhoul I, Hutchins L, Tackett A. Role of the EZH2 histone methyltransferase in melanoma. Pigment Cell Melanoma Res 2014 Nov; 27(6):1003-241; PMID:25346049; http://dx.doi.org/10.1111/pcmr.12321
  • Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res 2008 Dec 1; 647(1–2):21-9; PMID:18723033; http://dx.doi.org/10.1016/j.mrfmmm.2008.07.010
  • Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 2015 Jul 9; 523(7559):231-5; PMID:25970248; http://dx.doi.org/10.1038/nature14404
  • Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, Wang W, Sun Y, Zhao E, Vatan L, Szeliga W, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature 2015 Nov 12; 527(7577):249-53; PMID:26503055; http://dx.doi.org/10.1038/nature15520
  • Gallagher SJ, Tiffen JC, Hersey P. Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy. Cancers (Basel) 2015 Sep 25; 7(4):1959-82; PMID:26426052; http://dx.doi.org/10.3390/cancers7040870
  • McCabe MT, Graves AP, Ganji G, Diaz E, Halsey WS, Jiang Y, Smitheman KN, Ott HM, Pappalardi MB, Allen KE, et al. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2989-94; PMID:22323599; http://dx.doi.org/10.1073/pnas.1116418109
  • Verma SK, Tian X, LaFrance LV, Duquenne C, Suarez DP, Newlander KA, Romeril SP, Burgess JL, Grant SW, Brackley JA, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett 2012 Oct 19; 3(12):1091-6; PMID:24900432; http://dx.doi.org/10.1021/ml3003346
  • Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang KC, Xiao Y, Kadowaki T, Uesugi M, Kuznetsov G, Kumar N, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther 2014 Apr; 13(4):842-54; PMID:24563539; http://dx.doi.org/10.1158/1535-7163.MCT-13-0773
  • Ribrag V, Soria JC, Reyderman L, Chen R, Salazar P, Kumar N, et al. O7.2Phase 1 first-in-human study of the enhancer of zeste-homolog 2 (EZH2) histone methyl transferase inhibitor E7438. Ann Oncol 2015 Mar; 26(suppl 2):ii10; http://dx.doi.org/10.1093/annonc/mdv085.2
  • Morey L, Helin K. Polycomb group protein-mediated repression of transcription. Trends Biochem Sci. 2010 Jun; 35(6):323-32; PMID:20346678; http://dx.doi.org/10.1016/j.tibs.2010.02.009
  • Schuettengruber B, Cavalli G. Recruitment of polycomb group complexes and their role in the dynamic regulation of cell fate choice. Development 2009 Nov; 136(21):3531-42; PMID:19820181; http://dx.doi.org/10.1242/dev.033902
  • Pietersen AM, van Lohuizen M. Stem cell regulation by polycomb repressors: postponing commitment. Curr Opin Cell Biol 2008 Apr; 20(2):201-7; PMID:18291635; http://dx.doi.org/10.1016/j.ceb.2008.01.004
  • Ringrose L, Paro R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu Rev Genet 2004; 38:413-43; PMID:15568982; http://dx.doi.org/10.1146/annurev.genet.38.072902.091907
  • Muller J, Hart CM, Francis NJ, Vargas ML, Sengupta A, Wild B, Miller EL, O'Connor MB, Kingston RE, Simon JA. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 2002 Oct 18; 111(2):197-208; PMID:12408864; http://dx.doi.org/10.1016/S0092-8674(02)00976-5
  • Shao Z, Raible F, Mollaaghababa R, Guyon JR, Wu CT, Bender W, Kingston RE. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 1999 Jul 9; 98(1):37-46; PMID:10412979; http://dx.doi.org/10.1016/S0092-8674(00)80604-2
  • Surface LE, Thornton SR, Boyer LA. Polycomb group proteins set the stage for early lineage commitment. Cell Stem Cell 2010 Sep 3; 7(3):288-98; PMID:20804966; http://dx.doi.org/10.1016/j.stem.2010.08.004
  • Montgomery ND, Yee D, Chen A, Kalantry S, Chamberlain SJ, Otte AP, Magnuson T. The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation. Curr Biol 2005 May 24; 15(10):942-7; PMID:15916951; http://dx.doi.org/10.1016/j.cub.2005.04.051
  • Montgomery ND, Yee D, Montgomery SA, Magnuson T. Molecular and functional mapping of EED motifs required for PRC2-dependent histone methylation. J Mol Biol 2007 Dec 14; 374(5):1145-57; PMID:17997413; http://dx.doi.org/10.1016/j.jmb.2007.10.040
  • Pasini D, Bracken AP, Jensen MR, Lazzerini Denchi E, Helin K. Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J 2004 Oct 13; 23(20):4061-71; PMID:15385962; http://dx.doi.org/10.1038/sj.emboj.7600402
  • Cao R, Wang H, He J, Erdjument-Bromage H, Tempst P, Zhang Y. Role of hPHF1 in H3K27 methylation and Hox gene silencing. Mol Cell Biol. 2008 Mar; 28(5):1862-72; PMID:18086877; http://dx.doi.org/10.1128/MCB.01589-07
  • Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 2003 Oct 15; 22(20):5323-35; PMID:14532106; http://dx.doi.org/10.1093/emboj/cdg542
  • Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y. Role of histone H3 lysine 27 methylation in X inactivation. Science 2003 Apr 4; 300(5616):131-5; PMID:12649488; http://dx.doi.org/10.1126/science.1084274
  • Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev 2002 Nov 15; 16(22):2893-905; PMID:12435631; http://dx.doi.org/10.1101/gad.1035902
  • Eskeland R, Leeb M, Grimes GR, Kress C, Boyle S, Sproul D, Gilbert N, Fan Y, Skoultchi AI, Wutz A, et al. Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol Cell 2010 May 14; 38(3):452-64; PMID:20471950; http://dx.doi.org/10.1016/j.molcel.2010.02.032
  • Wang L, Brown JL, Cao R, Zhang Y, Kassis JA, Jones RS. Hierarchical recruitment of polycomb group silencing complexes. Mol Cell 2004 Jun 4; 14(5):637-46; PMID:15175158; http://dx.doi.org/10.1016/j.molcel.2004.05.009
  • Blackledge NP, Farcas AM, Kondo T, King HW, McGouran JF, Hanssen LL, Ito S, Cooper S, Kondo K, Koseki Y, et al. Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation. Cell 2014 Jun 5; 157(6):1445-59; PMID:24856970; http://dx.doi.org/10.1016/j.cell.2014.05.004
  • Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006 May 18; 441(7091):349-53; PMID:16625203; http://dx.doi.org/10.1038/nature04733
  • Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, et al. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 2008 Oct; 4(10):e1000242; PMID:18974828; http://dx.doi.org/10.1371/journal.pgen.1000242
  • Hu H, Yang Y, Ji Q, Zhao W, Jiang B, Liu R, Yuan J, Liu Q, Li X, Zou Y, et al. CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis. Cancer Cell 2012 Dec 11; 22(6):781-95; PMID:23238014; http://dx.doi.org/10.1016/j.ccr.2012.10.024
  • Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, Weisenberger DJ, Campan M, Young J, Jacobs I, et al. Epigenetic stem cell signature in cancer. Nat Genet 2007 Feb; 39(2):157-8; PMID:17200673; http://dx.doi.org/10.1038/ng1941
  • Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006 Feb 16; 439(7078):871-4; PMID:16357870; http://dx.doi.org/10.1038/nature04431
  • Lee ST, Li Z, Wu Z, Aau M, Guan P, Karuturi RK, Liou YC, Yu Q. Context-specific regulation of NF-kappaB target gene expression by EZH2 in breast cancers. Mol Cell 2011 Sep 2; 43(5):798-810; PMID:21884980; http://dx.doi.org/10.1016/j.molcel.2011.08.011
  • Shi B, Liang J, Yang X, Wang Y, Zhao Y, Wu H, Sun L, Zhang Y, Chen Y, Li R, et al. Integration of estrogen and Wnt signaling circuits by the polycomb group protein EZH2 in breast cancer cells. Mol Cell Biol 2007 Jul; 27(14):5105-19; PMID:17502350; http://dx.doi.org/10.1128/MCB.00162-07
  • Xu K, Wu ZJ, Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, et al. EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science 2012 Dec 14; 338(6113):1465-9; PMID:23239736; http://dx.doi.org/10.1126/science.1227604
  • Kampilafkos P, Melachrinou M, Kefalopoulou Z, Lakoumentas J, Sotiropoulou-Bonikou G. Epigenetic Modifications in Cutaneous Malignant Melanoma: EZH2, H3K4me2, and H3K27me3 Immunohistochemical Expression is Enhanced at the Invasion Front of the Tumor. Am J Dermatopathol 2015 Feb; 37(2):138-44; PMID:25614949; http://dx.doi.org/10.1097/DAD.0b013e31828a2d54
  • Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, et al. High frequency of BRAF mutations in nevi. Nat Genet 2003 Jan; 33(1):19-20; PMID:12447372; http://dx.doi.org/10.1038/ng1054
  • Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 2005 Aug 4; 436(7051):720-4; PMID:16079850; http://dx.doi.org/10.1038/nature03890
  • Fan T, Jiang S, Chung N, Alikhan A, Ni C, Lee CC, Hornyak TJ. EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression. Mol Cancer Res 2011 Apr; 9(4):418-29; PMID:21383005; http://dx.doi.org/10.1158/1541-7786.MCR-10-0511
  • Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003 Sep 30; 100(20):11606-11; PMID:14500907; http://dx.doi.org/10.1073/pnas.1933744100
  • McHugh JB, Fullen DR, Ma L, Kleer CG, Su LD. Expression of polycomb group protein EZH2 in nevi and melanoma. J Cutan Pathol 2007 Aug; 34(8):597-600; PMID:17640228; http://dx.doi.org/10.1111/j.1600-0560.2006.00678.x
  • Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K, et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 2008 Dec 12; 322(5908):1695-9; PMID:19008416; http://dx.doi.org/10.1126/science.1165395
  • Yamaguchi H, Hung MC. Regulation and Role of EZH2 in Cancer. Cancer Res Treat 2014 Jul; 46(3):209-22; PMID:25038756; http://dx.doi.org/10.4143/crt.2014.46.3.209
  • Zingg D, Debbache J, Schaefer SM, Tuncer E, Frommel SC, Cheng P, Arenas-Ramirez N, Haeusel J, Zhang Y, Bonalli M, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun. 2015 Jan 22; 6:6051; PMID:25609585; http://dx.doi.org/10.1038/ncomms7051
  • Chen X, Wang J, Shen H, Lu J, Li C, Hu DN, Dong XD, Yan D, Tu L, et al. Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci 2011 Mar 2; 52(3):1193-9; PMID:21051724; http://dx.doi.org/10.1167/iovs.10-5272
  • Bryant RJ, Cross NA, Eaton CL, Hamdy FC, Cunliffe VT. EZH2 promotes proliferation and invasiveness of prostate cancer cells. Prostate 2007 Apr 1; 67(5):547-56; PMID:17252556; http://dx.doi.org/10.1002/pros.20550
  • Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, et al. A landscape of driver mutations in melanoma. Cell 2012 Jul 20; 150(2):251-63; PMID:22817889; http://dx.doi.org/10.1016/j.cell.2012.06.024
  • Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 2012 Sep; 44(9):1006-14; PMID:22842228; http://dx.doi.org/10.1038/ng.2359
  • Schwabe M, Lubbert M. Epigenetic lesions in malignant melanoma. Curr Pharm Biotechnol 2007 Dec; 8(6):382-7; PMID:18289047; http://dx.doi.org/10.2174/138920107783018372
  • Sigalotti L, Covre A, Fratta E, Parisi G, Colizzi F, Rizzo A, Danielli R, Nicolay HJ, Coral S, Maio M, et al. Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies. J Transl Med 2010 Jun 11; 8:56, 5876-8-56; PMID:20540720; http://dx.doi.org/10.1186/1479-5876-8-56
  • Barsotti AM, Ryskin M, Zhong W, Zhang WG, Giannakou A, Loreth C, Diesl V, Follettie M, Golas J, Lee M, et al. Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth. Oncotarget 2015 Feb 20; 6(5):2928-38; PMID:25671303; http://dx.doi.org/10.18632/oncotarget.2758
  • Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012 Jul 6; 150(1):12-27; PMID:22770212; http://dx.doi.org/10.1016/j.cell.2012.06.013
  • Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med 2011 Mar; 17(3):330-9; PMID:21386836; http://dx.doi.org/10.1038/nm.2305
  • Varier RA, Timmers HT. Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta 2011 Jan; 1815(1):75-89; http://dx.doi.org/10.1016/j.bbcan.2010.10.002
  • Gil J, Peters G. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol 2006 Sep; 7(9):667-77; PMID:16921403; http://dx.doi.org/10.1038/nrm1987
  • Kia SK, Gorski MM, Giannakopoulos S, Verrijzer CP. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol Cell Biol 2008 May; 28(10):3457-64; PMID:18332116; http://dx.doi.org/10.1128/MCB.02019-07
  • Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Mönch K, Minucci S, Porse BT, Marine JC, et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 2007 Mar 1; 21(5):525-30; PMID:17344414; http://dx.doi.org/10.1101/gad.415507
  • Jacobs JJ, Kieboom K, Marino S, DePinho RA, van Lohuizen M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 1999 Jan 14; 397(6715):164-8; PMID:9923679; http://dx.doi.org/10.1038/16476
  • Tonini T, Bagella L, D'Andrilli G, Claudio PP, Giordano A. Ezh2 reduces the ability of HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A. Oncogene. 2004 Jun 17; 23(28):4930-7; PMID:15077161; http://dx.doi.org/10.1038/sj.onc.1207608
  • Tonini T, D'Andrilli G, Fucito A, Gaspa L, Bagella L. Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements. J Cell Physiol. 2008 Feb; 214(2):295-300; PMID:17786943; http://dx.doi.org/10.1002/jcp.21241
  • Bachmann IM, Straume O, Akslen LA. Altered expression of cell cycle regulators Cyclin D1, p14, p16, CDK4 and Rb in nodular melanomas. Int J Oncol 2004 Dec; 25(6):1559-65; PMID:15547691
  • Wu ZL, Zheng SS, Li ZM, Qiao YY, Aau MY, Yu Q. Polycomb protein EZH2 regulates E2F1-dependent apoptosis through epigenetically modulating Bim expression. Cell Death Differ 2010 May; 17(5):801-10; PMID:19893569; http://dx.doi.org/10.1038/cdd.2009.162
  • Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su IH, Hannon G, Tarakhovsky A, Fuchs E. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 2009 Mar 20; 136(6):1122-35; PMID:19303854; http://dx.doi.org/10.1016/j.cell.2008.12.043
  • Manning CS, Hooper S, Sahai EA. Intravital imaging of SRF and Notch signalling identifies a key role for EZH2 in invasive melanoma cells. Oncogene 2014 Nov 10; 34(33):4320-32; PMID:25381824; http://dx.doi.org/10.1038/onc.2014.362
  • Moriyama M, Osawa M, Mak SS, Ohtsuka T, Yamamoto N, Han H, Delmas V, Kageyama R, Beermann F, Larue L, et al. Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells. J Cell Biol 2006 May 8; 173(3):333-9; PMID:16651378; http://dx.doi.org/10.1083/jcb.200509084
  • Zabierowski SE, Baubet V, Himes B, Li L, Fukunaga-Kalabis M, Patel S, McDaid R, Guerra M, Gimotty P, Dahmane N, et al. Direct reprogramming of melanocytes to neural crest stem-like cells by one defined factor. Stem Cells 2011 Nov; 29(11):1752-62; PMID:21948558; http://dx.doi.org/10.1002/stem.740
  • Balasubramanian S, Adhikary G, Eckert RL. The Bmi-1 polycomb protein antagonizes the (−)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival. Carcinogenesis 2010 Mar; 31(3):496-503; PMID:20015867; http://dx.doi.org/10.1093/carcin/bgp314
  • Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009 Nov 25; 139(5):871-90; PMID:19945376; http://dx.doi.org/10.1016/j.cell.2009.11.007
  • Gupta PB, Kuperwasser C, Brunet JP, Ramaswamy S, Kuo WL, Gray JW, Naber SP, Weinberg RA. The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nat Genet 2005 Oct; 37(10):1047-54; PMID:16142232; http://dx.doi.org/10.1038/ng1634
  • Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008 May 16; 133(4):704-15; PMID:18485877; http://dx.doi.org/10.1016/j.cell.2008.03.027
  • Javelaud D, Alexaki VI, Mauviel A. Transforming growth factor-β in cutaneous melanoma. Pigment Cell Melanoma Res 2008 Apr; 21(2):123-32; PMID:18426405; http://dx.doi.org/10.1111/j.1755-148X.2008.00450.x
  • Caramel J, Papadogeorgakis E, Hill L, Browne GJ, Richard G, Wierinckx A, Saldanha G, Osborne J, Hutchinson P, Tse G, et al. A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell 2013 Oct 14; 24(4):466-80; PMID:24075834; http://dx.doi.org/10.1016/j.ccr.2013.08.018
  • Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schübeler D, van Nimwegen E, Christofori G. Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell 2013 Jun 10; 23(6):768-83; PMID:23764001; http://dx.doi.org/10.1016/j.ccr.2013.04.020
  • Hou P, Liu D, Dong J, Xing M. The BRAF(V600E) causes widespread alterations in gene methylation in the genome of melanoma cells. Cell Cycle 2012 Jan 15; 11(2):286-95; PMID:22189819; http://dx.doi.org/10.4161/cc.11.2.18707
  • Balint K, Xiao M, Pinnix CC, Soma A, Veres I, Juhasz I, Brown EJ, Capobianco AJ, Herlyn M, Liu ZJ. Activation of Notch1 signaling is required for β-catenin-mediated human primary melanoma progression. J Clin Invest 2005 Nov; 115(11):3166-76; PMID:16239965; http://dx.doi.org/10.1172/JCI25001
  • Pinner S, Jordan P, Sharrock K, Bazley L, Collinson L, Marais R, Bonvin E, Goding C, Sahai E. Intravital imaging reveals transient changes in pigment production and Brn2 expression during metastatic melanoma dissemination. Cancer Res 2009 Oct 15; 69(20):7969-77; PMID:19826052; http://dx.doi.org/10.1158/0008-5472.CAN-09-0781
  • Olson EN, Nordheim A. Linking actin dynamics and gene transcription to drive cellular motile functions. Nat Rev Mol Cell Biol 2010 May; 11(5):353-65; PMID:20414257; http://dx.doi.org/10.1038/nrm2890
  • Clark EA, Golub TR, Lander ES, Hynes RO. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 2000 Aug 3; 406(6795):532-5; PMID:10952316; http://dx.doi.org/10.1038/35020106
  • Medjkane S, Perez-Sanchez C, Gaggioli C, Sahai E, Treisman R. Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis. Nat Cell Biol 2009 Mar; 11(3):257-68; PMID:19198601; http://dx.doi.org/10.1038/ncb1833
  • Tiffen J, Gallagher SJ, Hersey P. EZH2: an emerging role in melanoma biology and strategies for targeted therapy. Pigment Cell Melanoma Res 2015 Jan; 28(1):21-30; PMID:24912396; http://dx.doi.org/10.1111/pcmr.12280
  • Hoek KS, Eichhoff OM, Schlegel NC, Dobbeling U, Kobert N, Schaerer L, Hemmi S, Dummer R. In vivo switching of human melanoma cells between proliferative and invasive states. Cancer Res 2008 Feb 1; 68(3):650-6; PMID:18245463; http://dx.doi.org/10.1158/0008-5472.CAN-07-2491
  • Carreira S, Goodall J, Denat L, Rodriguez M, Nuciforo P, Hoek KS, Testori A, Larue L, Goding CR. Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Genes Dev 2006 Dec 15; 20(24):3426-39; PMID:17182868; http://dx.doi.org/10.1101/gad.406406
  • Goodall J, Carreira S, Denat L, Kobi D, Davidson I, Nuciforo P, Sturm RA, Larue L, Goding CR. Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells. Cancer Res 2008 Oct 1; 68(19):7788-94; PMID:18829533; http://dx.doi.org/10.1158/0008-5472.CAN-08-1053
  • Sauka-Spengler T, Bronner-Fraser M. A gene regulatory network orchestrates neural crest formation. Nat Rev Mol Cell Biol 2008 Jul; 9(7):557-68; PMID:18523435; http://dx.doi.org/10.1038/nrm2428
  • Sauka-Spengler T, Bronner-Fraser M. Evolution of the neural crest viewed from a gene regulatory perspective. Genesis 2008 Nov; 46(11):673-82; PMID:19003930; http://dx.doi.org/10.1002/dvg.20436
  • Hornyak TJ, Hayes DJ, Chiu LY, Ziff EB. Transcription factors in melanocyte development: distinct roles for Pax-3 and Mitf. Mech Dev 2001 Mar; 101(1–2):47-59; PMID:11231058; http://dx.doi.org/10.1016/S0925-4773(00)00569-4
  • Tachibana M, Takeda K, Nobukuni Y, Urabe K, Long JE, Meyers KA, Aaronson SA, Miki T. Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics. Nat Genet 1996 Sep; 14(1):50-4; PMID:8782819; http://dx.doi.org/10.1038/ng0996-50
  • Lang D, Lu MM, Huang L, Engleka KA, Zhang M, Chu EY, Lipner S, Skoultchi A, Millar SE, Epstein JA. Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 2005 Feb 24; 433(7028):884-7; PMID:15729346; http://dx.doi.org/10.1038/nature03292
  • Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su IH, Hannon G, Tarakhovsky A, Fuchs E. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 2009 Mar 20; 136(6):1122-35; PMID:19303854; http://dx.doi.org/10.1016/j.cell.2008.12.043
  • Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, Karuturi RK, Tan PB, Liu ET, Yu Q. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 2007 May 1; 21(9):1050-63; PMID:17437993; http://dx.doi.org/10.1101/gad.1524107
  • Hoek KS, Goding CR. Cancer stem cells versus phenotype-switching in melanoma. Pigment Cell Melanoma Res 2010 Dec; 23(6):746-59; PMID:20726948; http://dx.doi.org/10.1111/j.1755-148X.2010.00757.x
  • Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 2006 May 1; 20(9):1123-36; PMID:16618801; http://dx.doi.org/10.1101/gad.381706
  • Kirmizis A, Bartley SM, Kuzmichev A, Margueron R, Reinberg D, Green R, Farnham PJ. Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev 2004 Jul 1; 18(13):1592-605; PMID:15231737; http://dx.doi.org/10.1101/gad.1200204
  • Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 2006 Apr 21; 125(2):301-13; PMID:16630818; http://dx.doi.org/10.1016/j.cell.2006.02.043
  • Pinnix CC, Lee JT, Liu ZJ, McDaid R, Balint K, Beverly LJ, Brafford PA, Xiao M, Himes B, Zabierowski SE, et al. Active Notch1 confers a transformed phenotype to primary human melanocytes. Cancer Res 2009 Jul 1; 69(13):5312-20; PMID:19549918; http://dx.doi.org/10.1158/0008-5472.CAN-08-3767
  • Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, et al. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res 2004 Aug 1; 64(15):5270-82; PMID:15289333; http://dx.doi.org/10.1158/0008-5472.CAN-04-0731
  • Liu ZJ, Xiao M, Balint K, Smalley KS, Brafford P, Qiu R, Pinnix CC, Li X, Herlyn M. Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res 2006 Apr 15; 66(8):4182-90; PMID:16618740; http://dx.doi.org/10.1158/0008-5472.CAN-05-3589
  • Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci U S A 2008 Apr 29; 105(17):6392-7; PMID:18427106; http://dx.doi.org/10.1073/pnas.0802047105
  • Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007 May 24; 447(7143):425-32; PMID:17522676; http://dx.doi.org/10.1038/nature05918
  • Velichutina I, Shaknovich R, Geng H, Johnson NA, Gascoyne RD, Melnick AM, Elemento O. EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood 2010 Dec 9; 116(24):5247-55; PMID:20736451; http://dx.doi.org/10.1182/blood-2010-04-280149
  • Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, Tarakhovsky A. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 2003 Feb; 4(2):124-31; PMID:12496962; http://dx.doi.org/10.1038/ni876
  • Su IH, Dobenecker MW, Dickinson E, Oser M, Basavaraj A, Marqueron R, Viale A, Reinberg D, Wülfing C, Tarakhovsky A. Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell 2005 May 6; 121(3):425-36; PMID:15882624; http://dx.doi.org/10.1016/j.cell.2005.02.029
  • He S, Wang J, Kato K, Xie F, Varambally S, Mineishi S, Kuick R, Mochizuki K, Liu Y, Nieves E, et al. Inhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cells. Blood 2012 Feb 2; 119(5):1274-82; PMID:22117046; http://dx.doi.org/10.1182/blood-2011-06-364422
  • Cuddapah S, Barski A, Zhao K. Epigenomics of T cell activation, differentiation, and memory. Curr Opin Immunol 2010 Jun; 22(3):341-7; PMID:20226645; http://dx.doi.org/10.1016/j.coi.2010.02.007
  • Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh TY, Watford WT, et al. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 2009 Jan 16; 30(1):155-67; PMID:19144320; http://dx.doi.org/10.1016/j.immuni.2008.12.009
  • Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 2012 Aug 16; 488(7411):404-8; PMID:22842901; http://dx.doi.org/10.1038/nature11262
  • De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell 2007 Sep 21; 130(6):1083-94; PMID:17825402; http://dx.doi.org/10.1016/j.cell.2007.08.019
  • Gobin SJ, Peijnenburg A, Keijsers V, van den Elsen PJ. Site α is crucial for two routes of IFN gamma-induced MHC class I transactivation: the ISRE-mediated route and a novel pathway involving CIITA. Immunity 1997 May; 6(5):601-11; PMID:9175838; http://dx.doi.org/10.1016/S1074-7613(00)80348-9
  • Morris AC, Beresford GW, Mooney MR, Boss JM. Kinetics of a gamma interferon response: expression and assembly of CIITA promoter IV and inhibition by methylation. Mol Cell Biol 2002 Jul; 22(13):4781-91; PMID:12052885; http://dx.doi.org/10.1128/MCB.22.13.4781-4791.2002
  • Holling TM, Bergevoet MW, Wilson L, Van Eggermond MC, Schooten E, Steenbergen RD, Snijders PJ, Jager MJ, Van den Elsen PJ. A role for EZH2 in silencing of IFN-gamma inducible MHC2TA transcription in uveal melanoma. J Immunol 2007 Oct 15; 179(8):5317-25; PMID:17911618; http://dx.doi.org/10.4049/jimmunol.179.8.5317
  • Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature 2007 Feb 22; 445(7130):851-7; PMID:17314971; http://dx.doi.org/10.1038/nature05661
  • Mueller DW, Bosserhoff AK. The evolving concept of ‘melano-miRs’-microRNAs in melanomagenesis. Pigment Cell Melanoma Res 2010 Oct; 23(5):620-6; PMID:20557479; http://dx.doi.org/10.1111/j.1755-148X.2010.00734.x
  • Mueller DW, Bosserhoff AK. Role of miRNAs in the progression of malignant melanoma. Br J Cancer 2009 Aug 18; 101(4):551-6; PMID:19638982; http://dx.doi.org/10.1038/sj.bjc.6605204
  • Bell RE, Levy C. The three M's: melanoma, microphthalmia-associated transcription factor and microRNA. Pigment Cell Melanoma Res 2011 Dec; 24(6):1088-106; PMID:22004179; http://dx.doi.org/10.1111/j.1755-148X.2011.00931.x
  • Philippidou D, Schmitt M, Moser D, Margue C, Nazarov PV, Muller A, Vallar L, Nashan D, Behrmann I, Kreis S. Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res 2010 May 15; 70(10):4163-73; PMID:20442294; http://dx.doi.org/10.1158/0008-5472.CAN-09-4512
  • Benetatos L, Voulgaris E, Vartholomatos G, Hatzimichael E. Non-coding RNAs and EZH2 interactions in cancer: long and short tales from the transcriptome. Int J Cancer 2013 Jul 15; 133(2):267-74; PMID:23001607; http://dx.doi.org/10.1002/ijc.27859
  • Guil S, Esteller M. DNA methylomes, histone codes and miRNAs: tying it all together. Int J Biochem Cell Biol 2009 Jan; 41(1):87-95; PMID:18834952; http://dx.doi.org/10.1016/j.biocel.2008.09.005
  • Dynek JN, Chan SM, Liu J, Zha J, Fairbrother WJ, Vucic D. Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas. Cancer Res 2008 May 1; 68(9):3124-32; PMID:18451137; http://dx.doi.org/10.1158/0008-5472.CAN-07-6622
  • Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 2005 Jul 7; 436(7047):117-22; PMID:16001072; http://dx.doi.org/10.1038/nature03664
  • Levy C, Khaled M, Fisher DE. MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 2006 Sep; 12(9):406-14; PMID:16899407; http://dx.doi.org/10.1016/j.molmed.2006.07.008
  • Luo C, Tetteh PW, Merz PR, Dickes E, Abukiwan A, Hotz-Wagenblatt A, Holland-Cunz S, Sinnberg T, Schittek B, Schadendorf D, et al. miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes. J Invest Dermatol 2013 Mar; 133(3):768-75; PMID:23151846; http://dx.doi.org/10.1038/jid.2012.357
  • Yan D, Dong XD, Chen X, Yao S, Wang L, Wang J, Wang C, Hu DN, Qu J, Tu L. Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development through MITF, BCL2 and cyclin D2. PLoS One 2012; 7(7):e40967; PMID:22848417; http://dx.doi.org/10.1371/journal.pone.0040967
  • Chen X, He D, Dong XD, Dong F, Wang J, Wang L, Tang J, Hu DN, Yan D, Tu L. MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma. Invest Ophthalmol Vis Sci 2013 Mar 1; 54(3):2248-56; PMID:23404119; http://dx.doi.org/10.1167/iovs.12-10977
  • Kosnopfel C, Sinnberg T, Schittek B. Y-box binding protein 1–a prognostic marker and target in tumour therapy. Eur J Cell Biol 2014 >Jan–Feb; 93(1–2):61-70; PMID:24461929; http://dx.doi.org/10.1016/j.ejcb.2013.11.007
  • Schultz J, Lorenz P, Gross G, Ibrahim S, Kunz M. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res 2008 May; 18(5):549-57; PMID:18379589; http://dx.doi.org/10.1038/cr.2008.45
  • Penna E, Orso F, Taverna D. miR-214 as a Key Hub that Controls Cancer Networks: Small Player, Multiple Functions. J Invest Dermatol 2015 Apr; 135(4):960-9; PMID:25501033; http://dx.doi.org/10.1038/jid.2014.479
  • Asangani IA, Harms PW, Dodson L, Pandhi M, Kunju LP, Maher CA, Fullen DR, Johnson TM, Giordano TJ, Palanisamy N, et al. Genetic and epigenetic loss of microRNA-31 leads to feed-forward expression of EZH2 in melanoma. Oncotarget 2012 Sep; 3(9):1011-25; PMID:22948084; http://dx.doi.org/10.18632/oncotarget.622
  • Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ. Use of chromatin immunoprecipitation to clone novel E2F target promoters. Mol Cell Biol 2001 Oct; 21(20):6820-32; PMID:11564866; http://dx.doi.org/10.1128/MCB.21.20.6820-6832.2001
  • Neri F, Zippo A, Krepelova A, Cherubini A, Rocchigiani M, Oliviero S. Myc regulates the transcription of the PRC2 gene to control the expression of developmental genes in embryonic stem cells. Mol Cell Biol 2012 Feb; 32(4):840-51; PMID:22184065; http://dx.doi.org/10.1128/MCB.06148-11
  • Fujii S, Fukamachi K, Tsuda H, Ito K, Ito Y, Ochiai A. RAS oncogenic signal upregulates EZH2 in pancreatic cancer. Biochem Biophys Res Commun 2012 Jan 20; 417(3):1074-9; PMID:22222375; http://dx.doi.org/10.1016/j.bbrc.2011.12.099
  • Liu S, Zhang B, Zhao Y, Chen P, Ji M, Hou P, Shi B. Association of BRAFV600E mutation with clinicopathological features of papillary thyroid carcinoma: a study on a Chinese population. Int J Clin Exp Pathol 2014 Sep 15; 7(10):6922-8; PMID:25400776
  • dos Santos NR, Torensma R, de Vries TJ, Schreurs MW, de Bruijn DR, Kater-Baats E, Ruiter DJ, Adema GJ, van Muijen GN, van Kessel AG. Heterogeneous expression of the SSX cancer/testis antigens in human melanoma lesions and cell lines. Cancer Res 2000 Mar 15; 60(6):1654-62; PMID:10749136
  • Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, Gusterson BA, Cooper CS. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 1994 Aug; 7(4):502-8; PMID:7951320; http://dx.doi.org/10.1038/ng0894-502
  • Garcia CB, Shaffer CM, Alfaro MP, Smith AL, Sun J, Zhao Z, Young PP, VanSaun MN, Eid JE. Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2. Oncogene 2012 May 3; 31(18):2323-34; PMID:21996728; http://dx.doi.org/10.1038/onc.2011.418
  • Gjerstorff MF, Relster MM, Greve KB, Moeller JB, Elias D, Lindgreen JN, Schmidt S, Mollenhauer J, Voldborg B, Pedersen CB, et al. SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression. Nucleic Acids Res 2014 Oct; 42(18):11433-46; PMID:25249625; http://dx.doi.org/10.1093/nar/gku852
  • Caretti G, Palacios D, Sartorelli V, Puri PL. Phosphoryl-EZH-ion. Cell Stem Cell 2011 Mar 4; 8(3):262-5; PMID:21362566; http://dx.doi.org/10.1016/j.stem.2011.02.012
  • Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, Zhou X, Bagchi A, Simon JA, Huang H. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol 2010 Nov; 12(11):1108-14; PMID:20935635; http://dx.doi.org/10.1038/ncb2116
  • Kaneko S, Li G, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev 2010 Dec 1; 24(23):2615-20; PMID:21123648; http://dx.doi.org/10.1101/gad.1983810
  • Wei Y, Chen YH, Li LY, Lang J, Yeh SP, Shi B, Yang CC, Yang JY, Lin CY, Lai CC, et al. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat Cell Biol 2011 Jan; 13(1):87-94; PMID:21131960; http://dx.doi.org/10.1038/ncb2139
  • Cha TL, Zhou BP, Xia W, Wu Y, Yang CC, Chen CT, Ping B, Otte AP, Hung MC. Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 2005 Oct 14; 310(5746):306-10; PMID:16224021; http://dx.doi.org/10.1126/science.1118947
  • Tiffen JC, Gunatilake D, Gallagher SJ, Gowrishankar K, Heinemann A, Cullinane C, Dutton-Regester K, Pupo GM, Strbenac D, Yang JY, et al. Targeting activating mutations of EZH2 leads to potent cell growth inhibition in human melanoma by derepression of tumor suppressor genes. Oncotarget 2015 Sep 29; 6(29):27023-36; PMID:26304929; http://dx.doi.org/10.18632/oncotarget.4809
  • ZH2 Inhibitor — EPZ-6438 for Non-Hodgkin Lymphoma and INI1-Deficient Tumors [Internet]. [2016].Available from: http://www.epizyme.com/programs/tazemetostat/
  • Masliah-Planchon J, Bieche I, Guinebretiere JM, Bourdeaut F, Delattre O. SWI/SNF chromatin remodeling and human malignancies. Annu Rev Pathol 2015; 10:145-71; PMID:25387058; http://dx.doi.org/10.1146/annurev-pathol-012414-040445

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.