69. Lai WKM, Pugh BF (2017) Understanding nucleosome dynamics and their links to gene
expression and DNA replication. Nat Rev Mol Cell Biol 18(9):548–562. https://doi.org/10.
1038/nrm.2017.47
70. Chan HM, Gu X-J, Huang Y, Li L, Mi Y, Qi W, Sendzik M, Sun Y, Wang L, Yu Z (2017)
Triazolopyrimidine compounds and uses thereof. United States of America Patent US9580437
(B2)
71. Stazi G, Zwergel C, Mai A, Valente S (2017) EZH2 inhibitors: a patent review (2014–2016).
Expert Opin Ther Pat 27(7):797–813. https://doi.org/10.1080/13543776.2017.1316976
72. Grinshtein N, Rioseco CC, Marcellus R, Uehling D, Aman A, Lun X, Muto O, Podmore L,
Lever J, Shen Y, Blough MD, Cairncross GJ, Robbins SM, Jones SJ, Marra MA, Al-Awar R,
Senger DL, Kaplan DR (2016) Small molecule epigenetic screen identifies novel EZH2 and
HDAC inhibitors that target glioblastoma brain tumor-initiating cells. Oncotarget 7(37):
59360–59376. https://doi.org/10.18632/oncotarget.10661
73. Frederiks F, Tzouros M, Oudgenoeg G, van Welsem T, Fornerod M, Krijgsveld J, van
Leeuwen F (2008) Nonprocessive methylation by Dot1 leads to functional redundancy of
histone H3K79 methylation states. Nat Struct Mol Biol 15(6):550–557. https://doi.org/10.
1038/nsmb.1432
74. Anglin JL, Song Y (2013) A medicinal chemistry perspective for targeting histone H3 lysine79 methyltransferase DOT1L. J Med Chem 56(22):8972–8983. https://doi.org/10.1021/
jm4007752
75. Woo Park J, Kim KB, Kim JY, Chae YC, Jeong OS, Seo SB (2015) RE-IIBP methylates
H3K79 and induces MEIS1-mediated apoptosis via H2BK120 ubiquitination by RNF20.
Sci Rep 5:12485. https://doi.org/10.1038/srep12485
76. Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y (2002)
Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.
Curr Biol 12(12):1052–1058
77. Min J, Feng Q, Li Z, Zhang Y, Xu RM (2003) Structure of the catalytic domain of human
DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112(5):711–723
78. Schubert HL, Blumenthal RM, Cheng X (2003) Many paths to methyltransfer: a chronicle of
convergence. Trends Biochem Sci 28(6):329–335. https://doi.org/10.1016/S0968-0004(03)
00090-2
79. Zee BM, Levin RS, Xu B, LeRoy G, Wingreen NS, Garcia BA (2010) In vivo residue-specific
histone methylation dynamics. J Biol Chem 285(5):3341–3350. https://doi.org/10.1074/jbc.
M109.063784
80. Jo SY, Granowicz EM, Maillard I, Thomas D, Hess JL (2011) Requirement for Dot1l in
murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood 117(18):
4759–4768. https://doi.org/10.1182/blood-2010-12-327668
81. Zhang L, Deng L, Chen F, Yao Y, Wu B, Wei L, Mo Q, Song Y (2014) Inhibition of histone
H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of
breast cancer. Oncotarget 5(21):10665–10677. https://doi.org/10.18632/oncotarget.2496
82. Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott
MP, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Tseng JC,
Kung AL, Armstrong SA, Copeland RA, Richon VM, Pollock RM (2011) Selective killing of
mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20(1):
53–65. https://doi.org/10.1016/j.ccr.2011.06.009
83. Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J,
Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E,
Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ,
Arrowsmith CH, Bradner JE, Schapira M (2012) Catalytic site remodelling of the DOT1L
methyltransferase by selective inhibitors. Nat Commun 3:1288. https://doi.org/10.1038/
ncomms2304
84. Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C, Olhava EJ, Daigle SR, Richon
VM, Pollock RM, Armstrong SA (2013) Abrogation of MLL-AF10 and CALM-AF10Lysine Methyltransferases and Their Inhibitors
153
expression and DNA replication. Nat Rev Mol Cell Biol 18(9):548–562. https://doi.org/10.
1038/nrm.2017.47
70. Chan HM, Gu X-J, Huang Y, Li L, Mi Y, Qi W, Sendzik M, Sun Y, Wang L, Yu Z (2017)
Triazolopyrimidine compounds and uses thereof. United States of America Patent US9580437
(B2)
71. Stazi G, Zwergel C, Mai A, Valente S (2017) EZH2 inhibitors: a patent review (2014–2016).
Expert Opin Ther Pat 27(7):797–813. https://doi.org/10.1080/13543776.2017.1316976
72. Grinshtein N, Rioseco CC, Marcellus R, Uehling D, Aman A, Lun X, Muto O, Podmore L,
Lever J, Shen Y, Blough MD, Cairncross GJ, Robbins SM, Jones SJ, Marra MA, Al-Awar R,
Senger DL, Kaplan DR (2016) Small molecule epigenetic screen identifies novel EZH2 and
HDAC inhibitors that target glioblastoma brain tumor-initiating cells. Oncotarget 7(37):
59360–59376. https://doi.org/10.18632/oncotarget.10661
73. Frederiks F, Tzouros M, Oudgenoeg G, van Welsem T, Fornerod M, Krijgsveld J, van
Leeuwen F (2008) Nonprocessive methylation by Dot1 leads to functional redundancy of
histone H3K79 methylation states. Nat Struct Mol Biol 15(6):550–557. https://doi.org/10.
1038/nsmb.1432
74. Anglin JL, Song Y (2013) A medicinal chemistry perspective for targeting histone H3 lysine79 methyltransferase DOT1L. J Med Chem 56(22):8972–8983. https://doi.org/10.1021/
jm4007752
75. Woo Park J, Kim KB, Kim JY, Chae YC, Jeong OS, Seo SB (2015) RE-IIBP methylates
H3K79 and induces MEIS1-mediated apoptosis via H2BK120 ubiquitination by RNF20.
Sci Rep 5:12485. https://doi.org/10.1038/srep12485
76. Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y (2002)
Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.
Curr Biol 12(12):1052–1058
77. Min J, Feng Q, Li Z, Zhang Y, Xu RM (2003) Structure of the catalytic domain of human
DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112(5):711–723
78. Schubert HL, Blumenthal RM, Cheng X (2003) Many paths to methyltransfer: a chronicle of
convergence. Trends Biochem Sci 28(6):329–335. https://doi.org/10.1016/S0968-0004(03)
00090-2
79. Zee BM, Levin RS, Xu B, LeRoy G, Wingreen NS, Garcia BA (2010) In vivo residue-specific
histone methylation dynamics. J Biol Chem 285(5):3341–3350. https://doi.org/10.1074/jbc.
M109.063784
80. Jo SY, Granowicz EM, Maillard I, Thomas D, Hess JL (2011) Requirement for Dot1l in
murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood 117(18):
4759–4768. https://doi.org/10.1182/blood-2010-12-327668
81. Zhang L, Deng L, Chen F, Yao Y, Wu B, Wei L, Mo Q, Song Y (2014) Inhibition of histone
H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of
breast cancer. Oncotarget 5(21):10665–10677. https://doi.org/10.18632/oncotarget.2496
82. Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott
MP, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Tseng JC,
Kung AL, Armstrong SA, Copeland RA, Richon VM, Pollock RM (2011) Selective killing of
mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20(1):
53–65. https://doi.org/10.1016/j.ccr.2011.06.009
83. Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J,
Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E,
Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ,
Arrowsmith CH, Bradner JE, Schapira M (2012) Catalytic site remodelling of the DOT1L
methyltransferase by selective inhibitors. Nat Commun 3:1288. https://doi.org/10.1038/
ncomms2304
84. Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C, Olhava EJ, Daigle SR, Richon
VM, Pollock RM, Armstrong SA (2013) Abrogation of MLL-AF10 and CALM-AF10Lysine Methyltransferases and Their Inhibitors
153