Histone-lysine N-methyltransferase EZH2

Details

Name
Histone-lysine N-methyltransferase EZH2
Synonyms
  • 2.1.1.43
  • Enhancer of zeste homolog 2
  • ENX-1
  • KMT6
  • Lysine N-methyltransferase 6
Gene Name
EZH2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051983|Histone-lysine N-methyltransferase EZH2
MGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQEW
KQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQNF
MVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNALGQ
YNDDDDDDDGDDPEEREEKQKDLEDHRDDKESRPPRKFPSDKIFEAISSMFPDKGTAEEL
KEKYKELTEQQLPGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFH
ATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRRGRLPN
NSSRPSTPTINVLESKDTDSDREAGTETGGENNDKEEEEKKDETSSSSEANSRCQTPIKM
KPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKESSIIAPA
PAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCDSSCPCVIAQ
NFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAADHWDSKNVS
CKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDK
YMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIGIFAKRAIQTGE
ELFFDYRYSQADALKYVGIEREMEIP
Number of residues
746
Molecular Weight
85362.435
Theoretical pI
Not Available
GO Classification
Functions
chromatin binding / chromatin DNA binding / DNA binding / histone methyltransferase activity / histone methyltransferase activity (H3-K27 specific) / histone-lysine N-methyltransferase activity / primary miRNA binding / promoter-specific chromatin binding / protein-lysine N-methyltransferase activity / ribonucleoprotein complex binding / RNA polymerase II core promoter sequence-specific DNA binding / RNA polymerase II proximal promoter sequence-specific DNA binding / RNA polymerase II transcription factor activity, sequence-specific DNA binding
Processes
cardiac muscle hypertrophy in response to stress / cellular response to hydrogen peroxide / cellular response to trichostatin A / cerebellar cortex development / chromatin organization / DNA methylation / G1 to G0 transition / hepatocyte homeostasis / hippocampus development / histone H3-K27 methylation / histone H3-K27 trimethylation / histone methylation / liver regeneration / negative regulation of DNA binding transcription factor activity / negative regulation of epidermal cell differentiation / negative regulation of G0 to G1 transition / negative regulation of G1/S transition of mitotic cell cycle / negative regulation of gene expression, epigenetic / negative regulation of retinoic acid receptor signaling pathway / negative regulation of striated muscle cell differentiation / negative regulation of transcription by RNA polymerase II / negative regulation of transcription elongation from RNA polymerase II promoter / negative regulation of transcription, DNA-templated / positive regulation of dendrite development / positive regulation of epithelial to mesenchymal transition / positive regulation of GTPase activity / positive regulation of MAP kinase activity / positive regulation of protein serine/threonine kinase activity / protein localization to chromatin / regulation of cell proliferation / regulation of circadian rhythm / regulation of gliogenesis / regulation of transcription, DNA-templated / response to estradiol / response to tetrachloromethane / rhythmic process / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / transcription, DNA-templated
Components
cytoplasm / ESC/E(Z) complex / nuclear chromatin / nucleoplasm / nucleus / pronucleus
General Function
Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription.
Specific Function
Chromatin binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0051984|Histone-lysine N-methyltransferase EZH2 (EZH2)
ATGGGCCAGACTGGGAAGAAATCTGAGAAGGGACCAGTTTGTTGGCGGAAGCGTGTAAAA
TCAGAGTACATGCGACTGAGACAGCTCAAGAGGTTCAGACGAGCTGATGAAGTAAAGAGT
ATGTTTAGTTCCAATCGTCAGAAAATTTTGGAAAGAACGGAAATCTTAAACCAAGAATGG
AAACAGCGAAGGATACAGCCTGTGCACATCCTGACTTCTGTGAGCTCATTGCGCGGGACT
AGGGAGTGTTCGGTGACCAGTGACTTGGATTTTCCAACACAAGTCATCCCATTAAAGACT
CTGAATGCAGTTGCTTCAGTACCCATAATGTATTCTTGGTCTCCCCTACAGCAGAATTTT
ATGGTGGAAGATGAAACTGTTTTACATAACATTCCTTATATGGGAGATGAAGTTTTAGAT
CAGGATGGTACTTTCATTGAAGAACTAATAAAAAATTATGATGGGAAAGTACACGGGGAT
AGAGAATGTGGGTTTATAAATGATGAAATTTTTGTGGAGTTGGTGAATGCCCTTGGTCAA
TATAATGATGATGACGATGATGATGATGGAGACGATCCTGAAGAAAGAGAAGAAAAGCAG
AAAGATCTGGAGGATCACCGAGATGATAAAGAAAGCCGCCCACCTCGGAAATTTCCTTCT
GATAAAATTTTTGAAGCCATTTCCTCAATGTTTCCAGATAAGGGCACAGCAGAAGAACTA
AAGGAAAAATATAAAGAACTCACCGAACAGCAGCTCCCAGGCGCACTTCCTCCTGAATGT
ACCCCCAACATAGATGGACCAAATGCTAAATCTGTTCAGAGAGAGCAAAGCTTACACTCC
TTTCATACGCTTTTCTGTAGGCGATGTTTTAAATATGACTGCTTCCTACATCCTTTTCAT
GCAACACCCAACACTTATAAGCGGAAGAACACAGAAACAGCTCTAGACAACAAACCTTGT
GGACCACAGTGTTACCAGCATTTGGAGGGAGCAAAGGAGTTTGCTGCTGCTCTCACCGCT
GAGCGGATAAAGACCCCACCAAAACGTCCAGGAGGCCGCAGAAGAGGACGGCTTCCCAAT
AACAGTAGCAGGCCCAGCACCCCCACCATTAATGTGCTGGAATCAAAGGATACAGACAGT
GATAGGGAAGCAGGGACTGAAACGGGGGGAGAGAACAATGATAAAGAAGAAGAAGAGAAG
AAAGATGAAACTTCGAGCTCCTCTGAAGCAAATTCTCGGTGTCAAACACCAATAAAGATG
AAGCCAAATATTGAACCTCCTGAGAATGTGGAGTGGAGTGGTGCTGAAGCCTCAATGTTT
AGAGTCCTCATTGGCACTTACTATGACAATTTCTGTGCCATTGCTAGGTTAATTGGGACC
AAAACATGTAGACAGGTGTATGAGTTTAGAGTCAAAGAATCTAGCATCATAGCTCCAGCT
CCCGCTGAGGATGTGGATACTCCTCCAAGGAAAAAGAAGAGGAAACACCGGTTGTGGGCT
GCACACTGCAGAAAGATACAGCTGAAAAAGGACGGCTCCTCTAACCATGTTTACAACTAT
CAACCCTGTGATCATCCACGGCAGCCTTGTGACAGTTCGTGCCCTTGTGTGATAGCACAA
AATTTTTGTGAAAAGTTTTGTCAATGTAGTTCAGAGTGTCAAAACCGCTTTCCGGGATGC
CGCTGCAAAGCACAGTGCAACACCAAGCAGTGCCCGTGCTACCTGGCTGTCCGAGAGTGT
GACCCTGACCTCTGTCTTACTTGTGGAGCCGCTGACCATTGGGACAGTAAAAATGTGTCC
TGCAAGAACTGCAGTATTCAGCGGGGCTCCAAAAAGCATCTATTGCTGGCACCATCTGAC
GTGGCAGGCTGGGGGATTTTTATCAAAGATCCTGTGCAGAAAAATGAATTCATCTCAGAA
TACTGTGGAGAGATTATTTCTCAAGATGAAGCTGACAGAAGAGGGAAAGTGTATGATAAA
TACATGTGCAGCTTTCTGTTCAACTTGAACAATGATTTTGTGGTGGATGCAACCCGCAAG
GGTAACAAAATTCGTTTTGCAAATCATTCGGTAAATCCAAACTGCTATGCAAAAGTTATG
ATGGTTAACGGTGATCACAGGATAGGTATTTTTGCCAAGAGAGCCATCCAGACTGGCGAA
GAGCTGTTTTTTGATTACAGATACAGCCAGGCTGATGCCCTGAAGTATGTCGGCATCGAA
AGAGAAATGGAAATCCCTTGA
Chromosome Location
7
Locus
7q36.1
External Identifiers
ResourceLink
UniProtKB IDQ15910
UniProtKB Entry NameEZH2_HUMAN
HGNC IDHGNC:3527
General References
  1. Chen H, Rossier C, Antonarakis SE: Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. Genomics. 1996 Nov 15;38(1):30-7. doi: 10.1006/geno.1996.0588. [Article]
  2. Laible G, Wolf A, Dorn R, Reuter G, Nislow C, Lebersorger A, Popkin D, Pillus L, Jenuwein T: Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres. EMBO J. 1997 Jun 2;16(11):3219-32. doi: 10.1093/emboj/16.11.3219. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Hobert O, Jallal B, Ullrich A: Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression. Mol Cell Biol. 1996 Jun;16(6):3066-73. [Article]
  7. Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontes M, Colleaux L: Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. Hum Mol Genet. 1998 Apr;7(4):679-84. [Article]
  8. Sewalt RG, van der Vlag J, Gunster MJ, Hamer KM, den Blaauwen JL, Satijn DP, Hendrix T, van Driel R, Otte AP: Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes. Mol Cell Biol. 1998 Jun;18(6):3586-95. [Article]
  9. van der Vlag J, Otte AP: Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet. 1999 Dec;23(4):474-8. doi: 10.1038/70602. [Article]
  10. Satijn DP, Hamer KM, den Blaauwen J, Otte AP: The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos. Mol Cell Biol. 2001 Feb;21(4):1360-9. doi: 10.1128/MCB.21.4.1360-1369.2001. [Article]
  11. 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. doi: 10.1101/gad.1035902. [Article]
  12. Sewalt RG, Lachner M, Vargas M, Hamer KM, den Blaauwen JL, Hendrix T, Melcher M, Schweizer D, Jenuwein T, Otte AP: Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins. Mol Cell Biol. 2002 Aug;22(15):5539-53. [Article]
  13. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y: Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002 Nov 1;298(5595):1039-43. doi: 10.1126/science.1076997. Epub 2002 Sep 26. [Article]
  14. 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. doi: 10.1093/emboj/cdg542. [Article]
  15. 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. doi: 10.1038/sj.emboj.7600402. Epub 2004 Sep 23. [Article]
  16. 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. doi: 10.1101/gad.1200204. [Article]
  17. Kuzmichev A, Jenuwein T, Tempst P, Reinberg D: Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell. 2004 Apr 23;14(2):183-93. [Article]
  18. Cao R, Zhang Y: SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol Cell. 2004 Jul 2;15(1):57-67. doi: 10.1016/j.molcel.2004.06.020. [Article]
  19. Tang X, Milyavsky M, Shats I, Erez N, Goldfinger N, Rotter V: Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene. 2004 Jul 29;23(34):5759-69. doi: 10.1038/sj.onc.1207706. [Article]
  20. Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R: The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005 Sep 23;122(6):835-47. [Article]
  21. Kuzmichev A, Margueron R, Vaquero A, Preissner TS, Scher M, Kirmizis A, Ouyang X, Brockdorff N, Abate-Shen C, Farnham P, Reinberg D: Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1859-64. Epub 2005 Jan 31. [Article]
  22. 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. doi: 10.1126/science.1118947. [Article]
  23. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  24. 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. doi: 10.1101/gad.381706. Epub 2006 Apr 17. [Article]
  25. Martin C, Cao R, Zhang Y: Substrate preferences of the EZH2 histone methyltransferase complex. J Biol Chem. 2006 Mar 31;281(13):8365-70. doi: 10.1074/jbc.M513425200. Epub 2006 Jan 23. [Article]
  26. Etchegaray JP, Yang X, DeBruyne JP, Peters AH, Weaver DR, Jenuwein T, Reppert SM: The polycomb group protein EZH2 is required for mammalian circadian clock function. J Biol Chem. 2006 Jul 28;281(30):21209-15. doi: 10.1074/jbc.M603722200. Epub 2006 May 22. [Article]
  27. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [Article]
  28. Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F: The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006 Feb 16;439(7078):871-4. Epub 2005 Dec 14. [Article]
  29. Kim DH, Villeneuve LM, Morris KV, Rossi JJ: Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nat Struct Mol Biol. 2006 Sep;13(9):793-7. doi: 10.1038/nsmb1142. Epub 2006 Aug 27. [Article]
  30. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y: pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes Dev. 2007 Jan 1;21(1):49-54. doi: 10.1101/gad.1499407. [Article]
  31. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Monch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K: 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. doi: 10.1101/gad.415507. [Article]
  32. Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, Bergman Y, Simon I, Cedar H: Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet. 2007 Feb;39(2):232-6. Epub 2006 Dec 31. [Article]
  33. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [Article]
  34. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  35. Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D: Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell. 2008 Nov 21;32(4):503-18. doi: 10.1016/j.molcel.2008.11.004. [Article]
  36. 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. doi: 10.1128/MCB.01589-07. Epub 2007 Dec 17. [Article]
  37. Sarma K, Margueron R, Ivanov A, Pirrotta V, Reinberg D: Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo. Mol Cell Biol. 2008 Apr;28(8):2718-31. doi: 10.1128/MCB.02017-07. Epub 2008 Feb 19. [Article]
  38. Riising EM, Boggio R, Chiocca S, Helin K, Pasini D: The polycomb repressive complex 2 is a potential target of SUMO modifications. PLoS One. 2008 Jul 16;3(7):e2704. doi: 10.1371/journal.pone.0002704. [Article]
  39. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  40. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  41. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  42. 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. doi: 10.1038/ncb2116. Epub 2010 Oct 10. [Article]
  43. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  44. Zhang Y, Yang X, Gui B, Xie G, Zhang D, Shang Y, Liang J: Corepressor protein CDYL functions as a molecular bridge between polycomb repressor complex 2 and repressive chromatin mark trimethylated histone lysine 27. J Biol Chem. 2011 Dec 9;286(49):42414-25. doi: 10.1074/jbc.M111.271064. Epub 2011 Oct 17. [Article]
  45. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  46. Lee JM, Lee JS, Kim H, Kim K, Park H, Kim JY, Lee SH, Kim IS, Kim J, Lee M, Chung CH, Seo SB, Yoon JB, Ko E, Noh DY, Kim KI, Kim KK, Baek SH: EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell. 2012 Nov 30;48(4):572-86. doi: 10.1016/j.molcel.2012.09.004. Epub 2012 Oct 11. [Article]
  47. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  48. Chu CS, Lo PW, Yeh YH, Hsu PH, Peng SH, Teng YC, Kang ML, Wong CH, Juan LJ: O-GlcNAcylation regulates EZH2 protein stability and function. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1355-60. doi: 10.1073/pnas.1323226111. Epub 2014 Jan 13. [Article]
  49. Hendriks IA, Lyon D, Young C, Jensen LJ, Vertegaal AC, Nielsen ML: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat Struct Mol Biol. 2017 Mar;24(3):325-336. doi: 10.1038/nsmb.3366. Epub 2017 Jan 23. [Article]
  50. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, Shashkin P, Charlot JF, Tcherpakov M, Corbett R, Tam A, Varhol R, Smailus D, Moksa M, Zhao Y, Delaney A, Qian H, Birol I, Schein J, Moore R, Holt R, Horsman DE, Connors JM, Jones S, Aparicio S, Hirst M, Gascoyne RD, Marra MA: Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010 Feb;42(2):181-5. doi: 10.1038/ng.518. Epub 2010 Jan 17. [Article]
  51. Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, Waghorn K, Zoi K, Ross FM, Reiter A, Hochhaus A, Drexler HG, Duncombe A, Cervantes F, Oscier D, Boultwood J, Grand FH, Cross NC: Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010 Aug;42(8):722-6. doi: 10.1038/ng.621. Epub 2010 Jul 4. [Article]
  52. Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, Marquez VE, Marra MA, Gascoyne RD, Humphries RK, Arrowsmith CH, Morin GB, Aparicio SA: Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood. 2011 Feb 24;117(8):2451-9. doi: 10.1182/blood-2010-11-321208. Epub 2010 Dec 29. [Article]
  53. Jankowska AM, Makishima H, Tiu RV, Szpurka H, Huang Y, Traina F, Visconte V, Sugimoto Y, Prince C, O'Keefe C, Hsi ED, List A, Sekeres MA, Rao A, McDevitt MA, Maciejewski JP: Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. Blood. 2011 Oct 6;118(14):3932-41. doi: 10.1182/blood-2010-10-311019. Epub 2011 Aug 9. [Article]
  54. Tatton-Brown K, Hanks S, Ruark E, Zachariou A, Duarte Sdel V, Ramsay E, Snape K, Murray A, Perdeaux ER, Seal S, Loveday C, Banka S, Clericuzio C, Flinter F, Magee A, McConnell V, Patton M, Raith W, Rankin J, Splitt M, Strenger V, Taylor C, Wheeler P, Temple KI, Cole T, Douglas J, Rahman N: Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height. Oncotarget. 2011 Dec;2(12):1127-33. doi: 10.18632/oncotarget.385. [Article]
  55. Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA, Chitayat D, Boycott KM, Weaver DD, Jones SJ: Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet. 2012 Jan 13;90(1):110-8. doi: 10.1016/j.ajhg.2011.11.018. Epub 2011 Dec 15. [Article]
  56. McCabe MT, Graves AP, Ganji G, Diaz E, Halsey WS, Jiang Y, Smitheman KN, Ott HM, Pappalardi MB, Allen KE, Chen SB, Della Pietra A 3rd, Dul E, Hughes AM, Gilbert SA, Thrall SH, Tummino PJ, Kruger RG, Brandt M, Schwartz B, Creasy CL: 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. doi: 10.1073/pnas.1116418109. Epub 2012 Feb 8. [Article]
  57. Al-Salem A, Alshammari MJ, Hassan H, Alazami AM, Alkuraya FS: Weaver syndrome and defective cortical development: a rare association. Am J Med Genet A. 2013 Jan;161A(1):225-7. doi: 10.1002/ajmg.a.35660. Epub 2012 Dec 13. [Article]
  58. Cohen AS, Yap DB, Lewis ME, Chijiwa C, Ramos-Arroyo MA, Tkachenko N, Milano V, Fradin M, McKinnon ML, Townsend KN, Xu J, Van Allen MI, Ross CJ, Dobyns WB, Weaver DD, Gibson WT: Weaver Syndrome-Associated EZH2 Protein Variants Show Impaired Histone Methyltransferase Function In Vitro. Hum Mutat. 2016 Mar;37(3):301-7. doi: 10.1002/humu.22946. Epub 2016 Jan 12. [Article]
  59. Imagawa E, Higashimoto K, Sakai Y, Numakura C, Okamoto N, Matsunaga S, Ryo A, Sato Y, Sanefuji M, Ihara K, Takada Y, Nishimura G, Saitsu H, Mizuguchi T, Miyatake S, Nakashima M, Miyake N, Soejima H, Matsumoto N: Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. Hum Mutat. 2017 Jun;38(6):637-648. doi: 10.1002/humu.23200. Epub 2017 Mar 15. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB14581CPI-1205investigationalyesinhibitorDetails
DB12887Tazemetostatapproved, investigationalyesinhibitorDetails