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Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase.

Couture JF, Collazo E, Brunzelle JS, Trievel RC
Genes Dev 19 1455-65 (2005)
Cited: 155 times
EuropePMC logo PMID: 15933070

Abstract

SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that is implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans. Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-adenosylhomocysteine. Histone H4 intercalates in the substrate-binding cleft as an extended parallel beta-strand. Residues preceding Lys-20 in H4 engage in an extensive array of salt bridge, hydrogen bond, and van der Waals interactions with hSET8, while the C-terminal residues bind through predominantly hydrophobic interactions. Mutational analysis of both the substrate-binding cleft and histone H4 reveals that interactions with residues in the N and C termini of the H4 peptide are critical for conferring substrate specificity. Finally, analysis of the product specificity indicates that hSET8 is a monomethylase, consistent with its role in the maintenance of Lys-20 monomethylation during cell division.

Reviews - 1zkk mentioned but not cited (6)

  1. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Black JC, Van Rechem C, Whetstine JR. Mol Cell 48 491-507 (2012)
  2. Inhibitors of Protein Methyltransferases and Demethylases. Kaniskan HÜ, Martini ML, Jin J. Chem Rev 118 989-1068 (2018)
  3. EZH2: biology, disease, and structure-based drug discovery. Tan JZ, Yan Y, Wang XX, Jiang Y, Xu HE. Acta Pharmacol Sin 35 161-174 (2014)
  4. The emerging role of lysine methyltransferase SETD8 in human diseases. Milite C, Feoli A, Viviano M, Rescigno D, Cianciulli A, Balzano AL, Mai A, Castellano S, Sbardella G. Clin Epigenetics 8 102 (2016)
  5. Dynamics of histone lysine methylation: structures of methyl writers and erasers. Upadhyay AK, Cheng X. Prog Drug Res 67 107-124 (2011)
  6. Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives. Andreoli F, Barbosa AJ, Parenti MD, Del Rio A. Curr Pharm Des 19 578-613 (2013)

Articles - 1zkk mentioned but not cited (17)

  1. Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Couture JF, Collazo E, Brunzelle JS, Trievel RC. Genes Dev 19 1455-1465 (2005)
  2. Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase SETD2. Zheng W, Ibáñez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A, Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M. J Am Chem Soc 134 18004-18014 (2012)
  3. Structural origins for the product specificity of SET domain protein methyltransferases. Couture JF, Dirk LM, Brunzelle JS, Houtz RL, Trievel RC. Proc Natl Acad Sci U S A 105 20659-20664 (2008)
  4. Structural insights into conformational stability of both wild-type and mutant EZH2 receptor. Aier I, Varadwaj PK, Raj U. Sci Rep 6 34984 (2016)
  5. Structure of the catalytic domain of EZH2 reveals conformational plasticity in cofactor and substrate binding sites and explains oncogenic mutations. Wu H, Zeng H, Dong A, Li F, He H, Senisterra G, Seitova A, Duan S, Brown PJ, Vedadi M, Arrowsmith CH, Schapira M. PLoS One 8 e83737 (2013)
  6. Targets in epigenetics: inhibiting the methyl writers of the histone code. Yost JM, Korboukh I, Liu F, Gao C, Jin J. Curr Chem Genomics 5 72-84 (2011)
  7. Molecular dynamics analysis to evaluate docking pose prediction. Sakano T, Mahamood MI, Yamashita T, Fujitani H. Biophys Physicobiol 13 181-194 (2016)
  8. The dynamic conformational landscape of the protein methyltransferase SETD8. Chen S, Wiewiora RP, Meng F, Babault N, Ma A, Yu W, Qian K, Hu H, Zou H, Wang J, Fan S, Blum G, Pittella-Silva F, Beauchamp KA, Tempel W, Jiang H, Chen K, Skene RJ, Zheng YG, Brown PJ, Jin J, Luo C, Chodera JD, Luo M. Elife 8 e45403 (2019)
  9. Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate. Girish TS, McGinty RK, Tan S. J Mol Biol 428 1531-1543 (2016)
  10. Structure-Based Design of a Covalent Inhibitor of the SET Domain-Containing Protein 8 (SETD8) Lysine Methyltransferase. Butler KV, Ma A, Yu W, Li F, Tempel W, Babault N, Pittella-Silva F, Shao J, Wang J, Luo M, Vedadi M, Brown PJ, Arrowsmith CH, Jin J. J Med Chem 59 9881-9889 (2016)
  11. Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase. Ho CH, Takizawa Y, Kobayashi W, Arimura Y, Kimura H, Kurumizaka H. Life Sci Alliance 4 e202000919 (2021)
  12. Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8. Judge RA, Zhu H, Upadhyay AK, Bodelle PM, Hutchins CW, Torrent M, Marin VL, Yu W, Vedadi M, Li F, Brown PJ, Pappano WN, Sun C, Petros AM. ACS Med Chem Lett 7 1102-1106 (2016)
  13. Deep Neural Network Classifier for Virtual Screening Inhibitors of (S)-Adenosyl-L-Methionine (SAM)-Dependent Methyltransferase Family. Li F, Wan X, Xing J, Tan X, Li X, Wang Y, Zhao J, Wu X, Liu X, Li Z, Luo X, Lu W, Zheng M. Front Chem 7 324 (2019)
  14. 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors. Xiang P, Jie H, Zhou Y, Yang B, Wang HJ, Hu J, Hu J, Yang SY, Zhao YL. Molecules 20 7620-7636 (2015)
  15. A Computational Approach Using Bioinformatics to Screening Drug Targets for Leishmania infantum Species. Chávez-Fumagalli MA, Schneider MS, Lage DP, Tavares GSV, Mendonça DVC, Santos TTO, Pádua RM, Machado-de-Ávila RA, Leite JPV, Coelho EAF. Evid Based Complement Alternat Med 2018 6813467 (2018)
  16. Distinct developmental phenotypes result from mutation of Set8/KMT5A and histone H4 lysine 20 in Drosophila melanogaster. Crain AT, Klusza S, Armstrong RL, Santa Rosa P, Temple BRS, Strahl BD, McKay DJ, Matera AG, Duronio RJ. Genetics 221 iyac054 (2022)
  17. Machine learning to estimate the local quality of protein crystal structures. Miyaguchi I, Sato M, Kashima A, Nakagawa H, Kokabu Y, Ma B, Matsumoto S, Tokuhisa A, Ohta M, Ikeguchi M. Sci Rep 11 23599 (2021)


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  1. Protein methyltransferases as a target class for drug discovery. Copeland RA, Solomon ME, Richon VM. Nat Rev Drug Discov 8 724-732 (2009)
  2. Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography. Thompson LH. Mutat Res 751 158-246 (2012)
  3. PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription. Beck DB, Oda H, Shen SS, Reinberg D. Genes Dev 26 325-337 (2012)
  4. SET for life: biochemical activities and biological functions of SET domain-containing proteins. Herz HM, Garruss A, Shilatifard A. Trends Biochem Sci 38 621-639 (2013)
  5. Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Bhat KP, Ümit Kaniskan H, Jin J, Gozani O. Nat Rev Drug Discov 20 265-286 (2021)
  6. Structure and function of SET and MYND domain-containing proteins. Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z. Int J Mol Sci 16 1406-1428 (2015)
  7. Emerging roles of lysine methylation on non-histone proteins. Zhang X, Huang Y, Shi X. Cell Mol Life Sci 72 4257-4272 (2015)
  8. Chemical and Biochemical Perspectives of Protein Lysine Methylation. Luo M. Chem Rev 118 6656-6705 (2018)
  9. Histone-modifying enzymes: encrypting an enigmatic epigenetic code. Couture JF, Trievel RC. Curr Opin Struct Biol 16 753-760 (2006)
  10. Structure and function of histone H3 lysine 9 methyltransferases and demethylases. Krishnan S, Horowitz S, Trievel RC. Chembiochem 12 254-263 (2011)
  11. Structural and functional coordination of DNA and histone methylation. Cheng X. Cold Spring Harb Perspect Biol 6 a018747 (2014)
  12. The multiple facets of histone H4-lysine 20 methylation. Yang H, Mizzen CA. Biochem Cell Biol 87 151-161 (2009)
  13. Structural dynamics of protein lysine methylation and demethylation. Cheng X, Zhang X. Mutat Res 618 102-115 (2007)
  14. Histone demethylases and cancer. Kampranis SC, Tsichlis PN. Adv Cancer Res 102 103-169 (2009)
  15. Histone H4 Lysine 20 (H4K20) Methylation, Expanding the Signaling Potential of the Proteome One Methyl Moiety at a Time. van Nuland R, Gozani O. Mol Cell Proteomics 15 755-764 (2016)
  16. A new regulator of the cell cycle: the PR-Set7 histone methyltransferase. Wu S, Rice JC. Cell Cycle 10 68-72 (2011)
  17. On your histone mark, SET, methylate! Binda O. Epigenetics 8 457-463 (2013)
  18. Molecular basis for substrate recognition by lysine methyltransferases and demethylases. Del Rizzo PA, Trievel RC. Biochim Biophys Acta 1839 1404-1415 (2014)
  19. Protein methylation and DNA repair. Lake AN, Bedford MT. Mutat Res 618 91-101 (2007)
  20. Regulation of chromatin structure via histone post-translational modification and the link to carcinogenesis. Thompson LL, Guppy BJ, Sawchuk L, Davie JR, McManus KJ. Cancer Metastasis Rev 32 363-376 (2013)
  21. SMYD3: a regulator of epigenetic and signaling pathways in cancer. Bernard BJ, Nigam N, Burkitt K, Saloura V. Clin Epigenetics 13 45 (2021)
  22. Protein and nucleic acid methylating enzymes: mechanisms and regulation. Le DD, Fujimori DG. Curr Opin Chem Biol 16 507-515 (2012)
  23. Tackling malignant melanoma epigenetically: histone lysine methylation. Orouji E, Utikal J. Clin Epigenetics 10 145 (2018)
  24. Repressive histone methylation: a case study in deterministic versus stochastic gene regulation. Lyons DB, Lomvardas S. Biochim Biophys Acta 1839 1373-1384 (2014)
  25. Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors. Milite C, Feoli A, Viviano M, Rescigno D, Mai A, Castellano S, Sbardella G. ChemMedChem 11 1680-1685 (2016)
  26. Histone 4 Lysine 20 Methylation: A Case for Neurodevelopmental Disease. Wickramasekara RN, Stessman HAF. Biology (Basel) 8 E11 (2019)
  27. Post-Translational Modifications of PCNA in Control of DNA Synthesis and DNA Damage Tolerance-the Implications in Carcinogenesis. Zhang S, Zhou T, Wang Z, Yi F, Li C, Guo W, Xu H, Cui H, Dong X, Liu J, Song X, Cao L. Int J Biol Sci 17 4047-4059 (2021)
  28. Methylation of histone 4's lysine 20: a critical analysis of the state of the field. Corvalan AZ, Coller HA. Physiol Genomics 53 22-32 (2021)
  29. The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review. Yang GF, Zhang X, Su YG, Zhao R, Wang YY. Cancer Cell Int 21 455 (2021)
  30. Therapeutical potential of deregulated lysine methyltransferase SMYD3 as a safe target for novel anticancer agents. Rajajeyabalachandran G, Kumar S, Murugesan T, Ekambaram S, Padmavathy R, Jegatheesan SK, Mullangi R, Rajagopal S. Expert Opin Ther Targets 21 145-157 (2017)
  31. Tailoring Proteins to Re-Evolve Nature: A Short Review. Jimenez-Rosales A, Flores-Merino MV. Mol Biotechnol 60 946-974 (2018)
  32. Roles for the methyltransferase SETD8 in DNA damage repair. Xu L, Zhang L, Sun J, Hu X, Kalvakolanu DV, Ren H, Guo B. Clin Epigenetics 14 34 (2022)
  33. The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications. Li Y, Ge K, Li T, Cai R, Chen Y. Protein Cell 14 165-179 (2023)

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  1. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G. Cell 127 1361-1373 (2006)
  2. Modulation of p53 function by SET8-mediated methylation at lysine 382. Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, Dutta S, Appella E, Gozani O. Mol Cell 27 636-646 (2007)
  3. Certain and progressive methylation of histone H4 at lysine 20 during the cell cycle. Pesavento JJ, Yang H, Kelleher NL, Mizzen CA. Mol Cell Biol 28 468-486 (2008)
  4. Structural biology of human H3K9 methyltransferases. Wu H, Min J, Lunin VV, Antoshenko T, Dombrovski L, Zeng H, Allali-Hassani A, Campagna-Slater V, Vedadi M, Arrowsmith CH, Plotnikov AN, Schapira M. PLoS One 5 e8570 (2010)
  5. Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks. Southall SM, Wong PS, Odho Z, Roe SM, Wilson JR. Mol Cell 33 181-191 (2009)
  6. The histone methyltransferase SET8 is required for S-phase progression. Jørgensen S, Elvers I, Trelle MB, Menzel T, Eskildsen M, Jensen ON, Helleday T, Helin K, Sørensen CS. J Cell Biol 179 1337-1345 (2007)
  7. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. Patel A, Dharmarajan V, Vought VE, Cosgrove MS. J Biol Chem 284 24242-24256 (2009)
  8. Structural basis for the methylation site specificity of SET7/9. Couture JF, Collazo E, Hauk G, Trievel RC. Nat Struct Mol Biol 13 140-146 (2006)
  9. The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation. Qiao Q, Li Y, Chen Z, Wang M, Reinberg D, Xu RM. J Biol Chem 286 8361-8368 (2011)
  10. Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation. Li Z, Nie F, Wang S, Li L. Proc Natl Acad Sci U S A 108 3116-3123 (2011)
  11. PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase. Tardat M, Murr R, Herceg Z, Sardet C, Julien E. J Cell Biol 179 1413-1426 (2007)
  12. Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability. Houston SI, McManus KJ, Adams MM, Sims JK, Carpenter PB, Hendzel MJ, Rice JC. J Biol Chem 283 19478-19488 (2008)
  13. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Yan Q, Dutt S, Xu R, Graves K, Juszczynski P, Manis JP, Shipp MA. Mol Cell 36 110-120 (2009)
  14. Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication. Huen MS, Sy SM, van Deursen JM, Chen J. J Biol Chem 283 11073-11077 (2008)
  15. Histone lysine methyltransferases and demethylases in Plasmodium falciparum. Cui L, Fan Q, Cui L, Miao J. Int J Parasitol 38 1083-1097 (2008)
  16. Preferential dimethylation of histone H4 lysine 20 by Suv4-20. Yang H, Pesavento JJ, Starnes TW, Cryderman DE, Wallrath LL, Kelleher NL, Mizzen CA. J Biol Chem 283 12085-12092 (2008)
  17. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Wu S, Wang W, Kong X, Congdon LM, Yokomori K, Kirschner MW, Rice JC. Genes Dev 24 2531-2542 (2010)
  18. Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein. Wang Y, Reddy B, Thompson J, Wang H, Noma K, Yates JR, Jia S. Mol Cell 33 428-437 (2009)
  19. A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. Sims JK, Houston SI, Magazinnik T, Rice JC. J Biol Chem 281 12760-12766 (2006)
  20. Structural and biochemical insights into MLL1 core complex assembly. Avdic V, Zhang P, Lanouette S, Groulx A, Tremblay V, Brunzelle J, Couture JF. Structure 19 101-108 (2011)
  21. Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. An S, Yeo KJ, Jeon YH, Song JJ. J Biol Chem 286 8369-8374 (2011)
  22. Structural and functional profiling of the human histone methyltransferase SMYD3. Foreman KW, Brown M, Park F, Emtage S, Harriss J, Das C, Zhu L, Crew A, Arnold L, Shaaban S, Tucker P. PLoS One 6 e22290 (2011)
  23. Arabidopsis Histone Lysine Methyltransferases. Pontvianne F, Blevins T, Pikaard CS. Adv Bot Res 53 1-22 (2010)
  24. Partitioning of the maize epigenome by the number of methyl groups on histone H3 lysines 9 and 27. Shi J, Dawe RK. Genetics 173 1571-1583 (2006)
  25. PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53. Cui G, Park S, Badeaux AI, Kim D, Lee J, Thompson JR, Yan F, Kaneko S, Yuan Z, Botuyan MV, Bedford MT, Cheng JQ, Mer G. Nat Struct Mol Biol 19 916-924 (2012)
  26. Structural Basis for Recognition of Ubiquitylated Nucleosome by Dot1L Methyltransferase. Anderson CJ, Baird MR, Hsu A, Barbour EH, Koyama Y, Borgnia MJ, McGinty RK. Cell Rep 26 1681-1690.e5 (2019)
  27. How do SET-domain protein lysine methyltransferases achieve the methylation state specificity? Revisited by Ab initio QM/MM molecular dynamics simulations. Hu P, Wang S, Zhang Y. J Am Chem Soc 130 3806-3813 (2008)
  28. Role for 53BP1 Tudor domain recognition of p53 dimethylated at lysine 382 in DNA damage signaling. Kachirskaia I, Shi X, Yamaguchi H, Tanoue K, Wen H, Wang EW, Appella E, Gozani O. J Biol Chem 283 34660-34666 (2008)
  29. Structural Chemistry of Human SET Domain Protein Methyltransferases. Schapira M. Curr Chem Genomics 5 85-94 (2011)
  30. Mechanism of histone methylation catalyzed by protein lysine methyltransferase SET7/9 and origin of product specificity. Guo HB, Guo H. Proc Natl Acad Sci U S A 104 8797-8802 (2007)
  31. Crystal structure of cardiac-specific histone methyltransferase SmyD1 reveals unusual active site architecture. Sirinupong N, Brunzelle J, Ye J, Pirzada A, Nico L, Yang Z. J Biol Chem 285 40635-40644 (2010)
  32. SET8-mediated methylations of histone H4 lysine 20 mark silent heterochromatic domains in apicomplexan genomes. Sautel CF, Cannella D, Bastien O, Kieffer S, Aldebert D, Garin J, Tardieux I, Belrhali H, Hakimi MA. Mol Cell Biol 27 5711-5724 (2007)
  33. A chemical method for labeling lysine methyltransferase substrates. Binda O, Boyce M, Rush JS, Palaniappan KK, Bertozzi CR, Gozani O. Chembiochem 12 330-334 (2011)
  34. PR-Set7-mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression. Congdon LM, Houston SI, Veerappan CS, Spektor TM, Rice JC. J Cell Biochem 110 609-619 (2010)
  35. Structural and biochemical studies of human lysine methyltransferase Smyd3 reveal the important functional roles of its post-SET and TPR domains and the regulation of its activity by DNA binding. Xu S, Wu J, Sun B, Zhong C, Ding J. Nucleic Acids Res 39 4438-4449 (2011)
  36. Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster. Sakaguchi A, Steward R. J Cell Biol 176 155-162 (2007)
  37. Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis: the case of histone lysine methyltransferase SET7/9. Wang S, Hu P, Zhang Y. J Phys Chem B 111 3758-3764 (2007)
  38. Catalytic roles for carbon-oxygen hydrogen bonding in SET domain lysine methyltransferases. Couture JF, Hauk G, Thompson MJ, Blackburn GM, Trievel RC. J Biol Chem 281 19280-19287 (2006)
  39. Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, Norris JL, Korboukh V, Tripathy A, Janzen WP, Arrowsmith CH, Frye SV, Vedadi M, Brown PJ, Jin J. J Med Chem 57 6822-6833 (2014)
  40. Regulation of H3K4 trimethylation via Cps40 (Spp1) of COMPASS is monoubiquitination independent: implication for a Phe/Tyr switch by the catalytic domain of Set1. Takahashi YH, Lee JS, Swanson SK, Saraf A, Florens L, Washburn MP, Trievel RC, Shilatifard A. Mol Cell Biol 29 3478-3486 (2009)
  41. Crystal structure and functional analysis of JMJD5 indicate an alternate specificity and function. Del Rizzo PA, Krishnan S, Trievel RC. Mol Cell Biol 32 4044-4052 (2012)
  42. Enzymatic mechanism and product specificity of SET-domain protein lysine methyltransferases. Zhang X, Bruice TC. Proc Natl Acad Sci U S A 105 5728-5732 (2008)
  43. Evolving Catalytic Properties of the MLL Family SET Domain. Zhang Y, Mittal A, Reid J, Reich S, Gamblin SJ, Wilson JR. Structure 23 1921-1933 (2015)
  44. Dominant alleles identify SET domain residues required for histone methyltransferase of Polycomb repressive complex 2. Joshi P, Carrington EA, Wang L, Ketel CS, Miller EL, Jones RS, Simon JA. J Biol Chem 283 27757-27766 (2008)
  45. Formulating a fluorogenic assay to evaluate S-adenosyl-L-methionine analogues as protein methyltransferase cofactors. Wang R, Ibáñez G, Islam K, Zheng W, Blum G, Sengelaub C, Luo M. Mol Biosyst 7 2970-2981 (2011)
  46. Solution structure of the Pdp1 PWWP domain reveals its unique binding sites for methylated H4K20 and DNA. Qiu Y, Zhang W, Zhao C, Wang Y, Wang W, Zhang J, Zhang Z, Li G, Shi Y, Tu X, Wu J. Biochem J 442 527-538 (2012)
  47. Structural insights of the specificity and catalysis of a viral histone H3 lysine 27 methyltransferase. Qian C, Wang X, Manzur K, Sachchidanand, Farooq A, Zeng L, Wang R, Zhou MM. J Mol Biol 359 86-96 (2006)
  48. SET7/9 catalytic mutants reveal the role of active site water molecules in lysine multiple methylation. Del Rizzo PA, Couture JF, Dirk LM, Strunk BS, Roiko MS, Brunzelle JS, Houtz RL, Trievel RC. J Biol Chem 285 31849-31858 (2010)
  49. Structural insights into estrogen receptor α methylation by histone methyltransferase SMYD2, a cellular event implicated in estrogen signaling regulation. Jiang Y, Trescott L, Holcomb J, Zhang X, Brunzelle J, Sirinupong N, Shi X, Yang Z. J Mol Biol 426 3413-3425 (2014)
  50. The histone modifications governing TFF1 transcription mediated by estrogen receptor. Li Y, Sun L, Zhang Y, Wang D, Wang F, Liang J, Gui B, Shang Y. J Biol Chem 286 13925-13936 (2011)
  51. Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2. Wu H, Siarheyeva A, Zeng H, Lam R, Dong A, Wu XH, Li Y, Schapira M, Vedadi M, Min J. FEBS Lett 587 3859-3868 (2013)
  52. Small-molecule inhibitors of SETD8 with cellular activity. Blum G, Ibáñez G, Rao X, Shum D, Radu C, Djaballah H, Rice JC, Luo M. ACS Chem Biol 9 2471-2478 (2014)
  53. Crystal structures of histone and p53 methyltransferase SmyD2 reveal a conformational flexibility of the autoinhibitory C-terminal domain. Jiang Y, Sirinupong N, Brunzelle J, Yang Z. PLoS One 6 e21640 (2011)
  54. SET/MYND Lysine Methyltransferases Regulate Gene Transcription and Protein Activity. Leinhart K, Brown M. Genes (Basel) 2 210-218 (2011)
  55. Degrees make all the difference: the multifunctionality of histone H4 lysine 20 methylation. Wang Y, Jia S. Epigenetics 4 273-276 (2009)
  56. Fluorescence-based methods for screening writers and readers of histone methyl marks. Allali-Hassani A, Wasney GA, Siarheyeva A, Hajian T, Arrowsmith CH, Vedadi M. J Biomol Screen 17 71-84 (2012)
  57. PR-Set7 establishes a repressive trans-tail histone code that regulates differentiation. Sims JK, Rice JC. Mol Cell Biol 28 4459-4468 (2008)
  58. Primers on chromatin. Lall S. Nat Struct Mol Biol 14 1110-1115 (2007)
  59. SET8 induces epithelial‑mesenchymal transition and enhances prostate cancer cell metastasis by cooperating with ZEB1. Hou L, Li Q, Yu Y, Li M, Zhang D. Mol Med Rep 13 1681-1688 (2016)
  60. Histone H4 Lys 20 methyltransferase SET8 promotes androgen receptor-mediated transcription activation in prostate cancer. Yao L, Li Y, Du F, Han X, Li X, Niu Y, Ren S, Sun Y. Biochem Biophys Res Commun 450 692-696 (2014)
  61. The SET8 H4K20 protein lysine methyltransferase has a long recognition sequence covering seven amino acid residues. Kudithipudi S, Dhayalan A, Kebede AF, Jeltsch A. Biochimie 94 2212-2218 (2012)
  62. A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases. Southall SM, Cronin NB, Wilson JR. Nucleic Acids Res 42 661-671 (2014)
  63. Free and chromatin-associated mono-, di-, and trimethylation of histone H4-lysine 20 during development and cell cycle progression. Karachentsev D, Druzhinina M, Steward R. Dev Biol 304 46-52 (2007)
  64. Horizontal gene transfer of epigenetic machinery and evolution of parasitism in the malaria parasite Plasmodium falciparum and other apicomplexans. Kishore SP, Stiller JW, Deitsch KW. BMC Evol Biol 13 37 (2013)
  65. Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogues. Chen D, Dong C, Dong G, Srinivasan K, Min J, Noinaj N, Huang R. J Med Chem 63 8419-8431 (2020)
  66. Identification and characterization of posttranslational modification-specific binding proteins in vivo by mammalian tethered catalysis. Spektor TM, Rice JC. Proc Natl Acad Sci U S A 106 14808-14813 (2009)
  67. Rubisco in complex with Rubisco large subunit methyltransferase. Raunser S, Magnani R, Huang Z, Houtz RL, Trievel RC, Penczek PA, Walz T. Proc Natl Acad Sci U S A 106 3160-3165 (2009)
  68. The ubiquitin-specific protease USP17 prevents cellular senescence by stabilizing the methyltransferase SET8 and transcriptionally repressing p21. Fukuura K, Inoue Y, Miyajima C, Watanabe S, Tokugawa M, Morishita D, Ohoka N, Komada M, Hayashi H. J Biol Chem 294 16429-16439 (2019)
  69. Two Loops Undergoing Concerted Dynamics Regulate the Activity of the ASH1L Histone Methyltransferase. Rogawski DS, Ndoj J, Cho HJ, Maillard I, Grembecka J, Cierpicki T. Biochemistry 54 5401-5413 (2015)
  70. Prognostic value of microRNA 502 binding site SNP in the 3'-untranslated region of the SET8 gene in patients with non-Hodgkin's lymphoma. Diao L, Su H, Wei G, Li T, Gao Y, Zhao G, Guo Z. Tumori 100 553-558 (2014)
  71. Systematic genetic interaction studies identify histone demethylase Utx as potential target for ameliorating Huntington's disease. Song W, Zsindely N, Faragó A, Marsh JL, Bodai L. Hum Mol Genet 27 649-666 (2018)
  72. Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells. Zhang X, Peng Y, Yuan Y, Gao Y, Hu F, Wang J, Zhu X, Feng X, Cheng Y, Wei Y, Fan X, Xie Y, Lv Y, Ashktorab H, Smoot D, Li S, Meltzer SJ, Hou G, Jin Z. Cell Death Dis 11 937 (2020)
  73. Structural Insights into Substrate Recognition and Catalysis in Outer Membrane Protein B (OmpB) by Protein-lysine Methyltransferases from Rickettsia. Abeykoon AH, Noinaj N, Choi BE, Wise L, He Y, Chao CC, Wang G, Gucek M, Ching WM, Chock PB, Buchanan SK, Yang DC. J Biol Chem 291 19962-19974 (2016)
  74. miR-502-mediated histone methyltransferase SET8 expression is associated with clear cell renal cell carcinoma risk. Zhang S, Guo Z, Xu J, Wang J, Zhang J, Cui L, Zhang H, Liu Y, Bai Y. Oncol Lett 14 7131-7138 (2017)
  75. Lysine Possesses the Optimal Chain Length for Histone Lysine Methyltransferase Catalysis. Temimi AHKA, Reddy YV, White PB, Guo H, Qian P, Mecinović J. Sci Rep 7 16148 (2017)
  76. A Role for Monomethylation of Histone H3-K27 in Gene Activity in Drosophila. Wang L, Joshi P, Miller EL, Higgins L, Slattery M, Simon JA. Genetics 208 1023-1036 (2018)
  77. Epigenetic Modifier SETD8 as a Therapeutic Target for High-Grade Serous Ovarian Cancer. Wada M, Kukita A, Sone K, Hamamoto R, Kaneko S, Komatsu M, Takahashi Y, Inoue F, Kojima M, Honjoh H, Taguchi A, Kashiyama T, Miyamoto Y, Tanikawa M, Tsuruga T, Mori-Uchino M, Wada-Hiraike O, Osuga Y, Fujii T. Biomolecules 10 E1686 (2020)
  78. Histone lysine methyltransferase Pr-set7/SETD8 promotes neural stem cell reactivation. Huang J, Gujar MR, Deng Q, Y Chia S, Li S, Tan P, Sung WK, Wang H. EMBO Rep 22 e50994 (2021)
  79. QM/MM MD and free energy simulations of G9a-like protein (GLP) and its mutants: understanding the factors that determine the product specificity. Chu Y, Yao J, Guo H. PLoS One 7 e37674 (2012)
  80. The UBC9 E2 SUMO conjugating enzyme binds the PR-Set7 histone methyltransferase to facilitate target gene repression. Spektor TM, Congdon LM, Veerappan CS, Rice JC. PLoS One 6 e22785 (2011)
  81. The histone H4 lysine 20 monomethyl mark, set by PR-Set7 and stabilized by L(3)mbt, is necessary for proper interphase chromatin organization. Sakaguchi A, Joyce E, Aoki T, Schedl P, Steward R. PLoS One 7 e45321 (2012)
  82. Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights. Müller MR, Burmeister A, Skowron MA, Stephan A, Bremmer F, Wakileh GA, Petzsch P, Köhrer K, Albers P, Nettersheim D. Clin Epigenetics 14 5 (2022)
  83. A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin β-cluster genes in the developing brain. Balan S, Iwayama Y, Ohnishi T, Fukuda M, Shirai A, Yamada A, Weirich S, Schuhmacher MK, Dileep KV, Endo T, Hisano Y, Kotoshiba K, Toyota T, Otowa T, Kuwabara H, Tochigi M, Watanabe A, Ohba H, Maekawa M, Toyoshima M, Sasaki T, Nakamura K, Tsujii M, Matsuzaki H, Zhang KYJ, Jeltsch A, Shinkai Y, Yoshikawa T. Mol Psychiatry 26 7550-7559 (2021)
  84. The identification and structure of an N-terminal PR domain show that FOG1 is a member of the PRDM family of proteins. Clifton MK, Westman BJ, Thong SY, O'Connell MR, Webster MW, Shepherd NE, Quinlan KG, Crossley M, Blobel GA, Mackay JP. PLoS One 9 e106011 (2014)
  85. H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos. Shikata D, Yamamoto T, Honda S, Ikeda S, Minami N. J Reprod Dev 66 411-419 (2020)
  86. A new layer of degradation mechanism for PR-Set7/Set8 during cell cycle. Zheng N, Dai X, Wang Z, Wei W. Cell Cycle 15 3042-3047 (2016)
  87. Investigation of the methylation of Numb by the SET8 protein lysine methyltransferase. Weirich S, Kusevic D, Kudithipudi S, Jeltsch A. Sci Rep 5 13813 (2015)
  88. The Histone Methyltransferase SETD8 Regulates the Expression of Tumor Suppressor Genes via H4K20 Methylation and the p53 Signaling Pathway in Endometrial Cancer Cells. Kukita A, Sone K, Kaneko S, Kawakami E, Oki S, Kojima M, Wada M, Toyohara Y, Takahashi Y, Inoue F, Tanimoto S, Taguchi A, Fukuda T, Miyamoto Y, Tanikawa M, Mori-Uchino M, Tsuruga T, Iriyama T, Matsumoto Y, Nagasaka K, Wada-Hiraike O, Oda K, Hamamoto R, Osuga Y. Cancers (Basel) 14 5367 (2022)
  89. Exploring the origin of the catalytic power and product specificity of SET domain protein methyltransferase. Lima AH, Alves CN, Prasad R, Lameira J. Mol Biosyst 12 2980-2983 (2016)
  90. Unique SMYD5 Structure Revealed by AlphaFold Correlates with Its Functional Divergence. Zhang Y, Alshammari E, Sobota J, Yang A, Li C, Yang Z. Biomolecules 12 783 (2022)
  91. Fasting Induces Hepatocellular Carcinoma Cell Apoptosis by Inhibiting SET8 Expression. Qi J, Chen X, Wu Q, Wang J, Zhang H, Mao A, Zhu M, Miao C. Oxid Med Cell Longev 2020 3985089 (2020)
  92. Structural Analysis of SMYD3 Lysine Methyltransferase for the Development of Competitive and Specific Enzyme Inhibitors. Jarrell DK, Hassell KN, Alshiraihi I, Crans DC, Brown MA. Diseases 10 4 (2021)
  93. Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2. Kalinić M, Zloh M, Erić S. J Comput Aided Mol Des 28 1109-1128 (2014)
  94. Tyrosine Kinase Inhibitor Imatinib Mesylate Alters DMBA-Induced Early Onco/Suppressor Gene Expression with Tissue-Specificity in Mice. Gergely PA, Murnyák B, Bencze J, Kurucz A, Varjas T, Gombos K, Hortobágyi T. Biomed Res Int 2019 8670398 (2019)
  95. Poly ADP-ribosylation of SET8 leads to aberrant H4K20 methylation in mammalian nuclear genome. Estève PO, Sen S, Vishnu US, Ruse C, Chin HG, Pradhan S. Commun Biol 5 1292 (2022)
  96. QM/MM MD and Free Energy Simulation Study of Methyl Transfer Processes Catalyzed by PKMTs and PRMTs. Chu Y, Guo H. Interdiscip Sci 7 309-318 (2015)
  97. Mechanism of SET8 Activates the Nrf2-KEAP1-ARE Signaling Pathway to Promote the Recovery of Motor Function after Spinal Cord Injury. Li X, Qian Y, Shen W, Zhang S, Han H, Zhang Y, Liu S, Lv S, Zhang X. Mediators Inflamm 2023 4420592 (2023)
  98. Parallels and contrasts between the cnidarian and bilaterian maternal-to-zygotic transition are revealed in Hydractinia embryos. Ayers TN, Nicotra ML, Lee MT. PLoS Genet 19 e1010845 (2023)
  99. The Mycobacterium tuberculosis methyltransferase Rv2067c manipulates host epigenetic programming to promote its own survival. Singh PR, Dadireddy V, Udupa S, Kalladi SM, Shee S, Khosla S, Rajmani RS, Singh A, Ramakumar S, Nagaraja V. Nat Commun 14 8497 (2023)


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