Inhibition of histone H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of breast cancer

Histone lysine methylation regulates gene expression and cancer initiation. Bioinformatics analysis suggested that DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, plays a potentially important role in breast cancer. DOT1L inhibition selectively inhibited proliferation, self-renewal, metastat...

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Published inOncotarget Vol. 5; no. 21; pp. 10665 - 10677
Main Authors Zhang, Li, Deng, Lisheng, Chen, Fengju, Yao, Yuan, Wu, Bulan, Wei, Liping, Mo, Qianxing, Song, Yongcheng
Format Journal Article
LanguageEnglish
Published United States Impact Journals LLC 15.11.2014
Subjects
Adenosine - analogs & derivatives
Adenosine - pharmacology
Animals
Apoptosis - drug effects
Blotting, Western
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Cycle - drug effects
Cell Differentiation - drug effects
Cell Movement - drug effects
Cell Proliferation - drug effects
DNA Methylation
Enzyme Inhibitors - pharmacology
Female
Flow Cytometry
Histones - chemistry
Histones - genetics
Histones - metabolism
Humans
Immunoenzyme Techniques
Lysine
Methyltransferases - antagonists & inhibitors
Methyltransferases - genetics
Methyltransferases - metabolism
Mice
Mice, Nude
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Real-Time Polymerase Chain Reaction
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Online AccessGet full text

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Abstract Histone lysine methylation regulates gene expression and cancer initiation. Bioinformatics analysis suggested that DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, plays a potentially important role in breast cancer. DOT1L inhibition selectively inhibited proliferation, self-renewal, metastatic potential of breast cancer cells and induced cell differentiation. In addition, inhibitors of S-adenosylhomocysteine hydrolase (SAHH), such as neplanocin and 3-deazaneplanocin, also inhibited both H3K79 methylation and proliferation of breast cancer cells in vitro and in vivo. The activity of SAHH inhibitors was previously attributed to inhibition of H3K27 methyltransferase EZH2. However, inhibition of EZH2 by a specific inhibitor did not contribute to cell death. SAHH inhibitors had only weak activity against H3K27 methylation and their activity is therefore mainly due to DOT1L/H3K79 methylation inhibition. Overall, we showed that DOT1L is a potential drug target for breast cancer.
AbstractList Histone lysine methylation regulates gene expression and cancer initiation. Bioinformatics analysis suggested that DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, plays a potentially important role in breast cancer. DOT1L inhibition selectively inhibited proliferation, self-renewal, metastatic potential of breast cancer cells and induced cell differentiation. In addition, inhibitors of S-adenosylhomocysteine hydrolase (SAHH), such as neplanocin and 3-deazaneplanocin, also inhibited both H3K79 methylation and proliferation of breast cancer cells in vitro and in vivo. The activity of SAHH inhibitors was previously attributed to inhibition of H3K27 methyltransferase EZH2. However, inhibition of EZH2 by a specific inhibitor did not contribute to cell death. SAHH inhibitors had only weak activity against H3K27 methylation and their activity is therefore mainly due to DOT1L/H3K79 methylation inhibition. Overall, we showed that DOT1L is a potential drug target for breast cancer.
Author Song, Yongcheng
Wu, Bulan
Wei, Liping
Yao, Yuan
Zhang, Li
Deng, Lisheng
Mo, Qianxing
Chen, Fengju
AuthorAffiliation 2 Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
1 Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
3 Department of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USA
AuthorAffiliation_xml – name: 3 Department of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USA
– name: 1 Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
– name: 2 Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
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  givenname: Li
  surname: Zhang
  fullname: Zhang, Li
  organization: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
– sequence: 2
  givenname: Lisheng
  surname: Deng
  fullname: Deng, Lisheng
  organization: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
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  givenname: Fengju
  surname: Chen
  fullname: Chen, Fengju
  organization: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
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  fullname: Yao, Yuan
  organization: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
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  fullname: Wu, Bulan
  organization: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
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  surname: Mo
  fullname: Mo, Qianxing
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– sequence: 8
  givenname: Yongcheng
  surname: Song
  fullname: Song, Yongcheng
  organization: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
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Cites_doi 10.1101/gad.1898410
10.1038/ncomms2304
10.1093/hmg/ddl444
10.1182/blood-2013-04-497644
10.1021/jm4007752
10.1016/S0021-9258(17)43053-5
10.1136/jcp.2011.090456
10.1158/1078-0432.CCR-09-1532
10.1016/S0092-8674(02)00759-6
10.1101/gad.1061803
10.1016/0006-2952(86)90774-4
10.1111/cbdd.12050
10.1016/j.cell.2007.01.029
10.1101/gad.2057811
10.1200/JCO.2008.18.1370
10.1038/cr.2011.115
10.1016/j.cell.2008.03.027
10.1128/MCB.02076-07
10.1371/journal.pbio.1000249
10.1038/ng1972
10.1038/nrd2974
10.1182/blood-2010-03-276501
10.1073/pnas.0905718106
10.1007/s10911-010-9173-1
10.1016/j.stem.2007.08.014
10.1016/j.ccr.2011.06.009
10.1021/jm00127a007
10.18632/oncotarget.1503
10.1038/nchembio.1084
10.1038/nsmb1337
10.1016/j.mrfmmm.2008.07.010
10.1016/j.cell.2007.02.005
10.1038/nmeth0409-239
10.1073/pnas.0530291100
10.1016/S0960-9822(02)00901-6
10.1182/blood-2007-05-090514
10.1074/jbc.M111.328138
10.1016/j.cell.2005.02.020
10.1073/pnas.1933744100
10.1038/nature04431
10.1021/ja206312b
10.1101/gad.1524107
10.1007/s10549-010-0982-0
10.1111/j.1747-0285.2011.01135.x
10.1016/j.tet.2007.06.100
10.1021/jm300917h
10.1016/j.ccr.2008.10.001
10.1016/j.molcel.2010.01.026
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References 19204204 - J Clin Oncol. 2009 Mar 10;27(8):1160-7
20798234 - Blood. 2010 Nov 25;116(22):4483-91
20556507 - Breast Cancer Res Treat. 2011 May;127(1):109-19
17855633 - Blood. 2007 Dec 15;110(13):4445-54
19666588 - Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13820-5
22190683 - J Biol Chem. 2012 Feb 17;287(8):5588-99
21769133 - Cell Res. 2011 Sep;21(9):1370-3
14500907 - Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11606-11
19956800 - PLoS Biol. 2009 Nov;7(11):e1000249
23801631 - Blood. 2013 Aug 8;122(6):1017-25
6707008 - J Biol Chem. 1984 Apr 10;259(7):4353-8
12756227 - Genes Dev. 2003 May 15;17(10):1253-70
17320507 - Cell. 2007 Feb 23;128(4):693-705
19333237 - Nat Methods. 2009 Apr;6(4):239-40
3943084 - Cancer Res. 1986 Mar;46(3):1063-7
22978415 - Chem Biol Drug Des. 2012 Dec;80(6):971-80
22924785 - J Med Chem. 2012 Sep 27;55(18):8066-74
12629218 - Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
15851025 - Cell. 2005 Apr 22;121(2):167-78
18285465 - Mol Cell Biol. 2008 Apr;28(8):2825-39
19721445 - Nat Rev Drug Discov. 2009 Sep;8(9):724-32
23023262 - Nat Chem Biol. 2012 Nov;8(11):890-6
20103682 - Clin Cancer Res. 2010 Feb 1;16(3):876-87
21680574 - J Clin Pathol. 2011 Nov;64(11):937-46
23250418 - Nat Commun. 2012;3:1288
2544721 - J Med Chem. 1989 Jul;32(7):1442-6
17320506 - Cell. 2007 Feb 23;128(4):683-92
17984963 - Nat Struct Mol Biol. 2007 Nov;14(11):1008-16
18977325 - Cancer Cell. 2008 Nov 4;14(5):355-68
3790170 - Biochem Pharmacol. 1986 Dec 15;35(24):4523-7
16357870 - Nature. 2006 Feb 16;439(7078):871-4
20354771 - J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):253-60
12086673 - Cell. 2002 Jun 14;109(6):745-56
18371393 - Cell Stem Cell. 2007 Nov;1(5):555-67
24345883 - Oncotarget. 2013 Dec;4(12):2532-49
17135274 - Hum Mol Genet. 2007 Jan 1;16(1):92-106
21741596 - Cancer Cell. 2011 Jul 12;20(1):53-65
20203130 - Genes Dev. 2010 Mar 15;24(6):574-89
21564555 - Chem Biol Drug Des. 2011 Aug;78(2):199-210
18485877 - Cell. 2008 May 16;133(4):704-15
17437993 - Genes Dev. 2007 May 1;21(9):1050-63
23879463 - J Med Chem. 2013 Nov 27;56(22):8972-83
3408743 - Biochim Biophys Acta. 1988 Aug 19;971(1):38-45
18723033 - Mutat Res. 2008 Dec 1;647(1-2):21-9
12123582 - Curr Biol. 2002 Jun 25;12(12):1052-8
21936531 - J Am Chem Soc. 2011 Oct 26;133(42):16746-9
16417656 - Breast Cancer Res. 2006;8(1):R7
21724828 - Genes Dev. 2011 Jul 1;25(13):1345-58
20159561 - Mol Cell. 2010 Feb 12;37(3):429-37
17211412 - Nat Genet. 2007 Feb;39(2):237-42
Shilatifard (3) 2007; 14
Florens (13) 2010; 37
Smalley (27) 2006; 8
Boriack-Sjodin (16) 2011; 20
Slany (10) 2009; 7
Jiang (17) 2012; 55
Kuhn (21) 2009; 6
Federation (18) 2012; 3
Clarke (25) 2003; 100
Sreekumar (9) 2007; 110
Song (41) 2013; 122
Lee (38) 2007; 21
Kim (20) 2012; 287
Didelot (47) 2006; 439
Cope (48) 2007; 39
Rosen (30) 2010; 15
Sjolund (31) 2009; 106
Kaiser (36) 1988; 971
Richon (4) 2009; 8
Gottschling (5) 2002; 109
Marquez (33) 1986; 35
Sinha (15) 2008; 14
Zhuo (6) 2008; 28
Polyak (23) 2010; 16
Patel-Thombre U. Neplanocin (32) 1984; 259
Baylin (2) 2007; 128
Vickery (22) 2009; 27
Cameselle-Teijeiro (24) 2011; 64
Coffield (14) 2005; 121
ZhangM, Jacob (43) 2010; 116
Song (19) 2013; 56
Sakurai (37) 1986; 46
Klaus (40) 2012; 8
Cheng (46) 2013; 4
Kawamura (28) 2003; 17
Strazewski (50) 2007; 63
McPherson (51) 1989; 32
Zhang (42) 2011; 21
Zhang (7) 2011; 25
Elliston (35) 2011; 78
Zhang (12) 2010; 24
Brown (26) 2007; 1
Lange (45) 2008; 647
Davies (11) 2007; 16
Crabb (39) 2011; 127
Struhl (8) 2002; 12
Anglin (34) 2011; 133
Zhou (29) 2008; 133
Kouzarides (1) 2007; 128
Tomlins (44) 2003; 100
Wigle (49) 2012; 80
References_xml – volume: 24
  start-page: 574
  year: 2010
  ident: 12
  article-title: Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom)
  publication-title: Genes Dev
  doi: 10.1101/gad.1898410
  contributor:
    fullname: Zhang
– volume: 3
  start-page: 1288
  year: 2012
  ident: 18
  article-title: Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors
  publication-title: Nat Commun
  doi: 10.1038/ncomms2304
  contributor:
    fullname: Federation
– volume: 8
  start-page: R7
  year: 2006
  ident: 27
  article-title: CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells
  publication-title: Breast Cancer Res
  contributor:
    fullname: Smalley
– volume: 16
  start-page: 92
  year: 2007
  ident: 11
  article-title: The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddl444
  contributor:
    fullname: Davies
– volume: 122
  start-page: 1017
  year: 2013
  ident: 41
  article-title: Potent inhibition of DOT1L as treatment of MLL-fusion leukemia
  publication-title: Blood
  doi: 10.1182/blood-2013-04-497644
  contributor:
    fullname: Song
– volume: 56
  start-page: 8972
  year: 2013
  ident: 19
  article-title: A medicinal chemistry perspective for targeting histone H3 lysine-79 methyltransferase DOT1L
  publication-title: J Med Chem
  doi: 10.1021/jm4007752
  contributor:
    fullname: Song
– volume: 259
  start-page: 4353
  year: 1984
  ident: 32
  article-title: A potent inhibitor of S-adenosylhomocysteine hydrolase and of vaccinia virus multiplication in mouse L929 cells
  publication-title: J Biol Chem
  doi: 10.1016/S0021-9258(17)43053-5
  contributor:
    fullname: Patel-Thombre U. Neplanocin
– volume: 64
  start-page: 937
  year: 2011
  ident: 24
  article-title: Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype
  publication-title: J Clin Pathol
  doi: 10.1136/jcp.2011.090456
  contributor:
    fullname: Cameselle-Teijeiro
– volume: 16
  start-page: 876
  year: 2010
  ident: 23
  article-title: Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-09-1532
  contributor:
    fullname: Polyak
– volume: 109
  start-page: 745
  year: 2002
  ident: 5
  article-title: Dot1p modulates silencing in yeast by methylation of the nucleosome core
  publication-title: Cell
  doi: 10.1016/S0092-8674(02)00759-6
  contributor:
    fullname: Gottschling
– volume: 17
  start-page: 1253
  year: 2003
  ident: 28
  article-title: In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells
  publication-title: Genes Dev
  doi: 10.1101/gad.1061803
  contributor:
    fullname: Kawamura
– volume: 35
  start-page: 4523
  year: 1986
  ident: 33
  article-title: 3-Deazaneplanocin A: a new inhibitor of S-adenosylhomocysteine synthesis and its effects in human colon carcinoma cells
  publication-title: Biochem Pharmacol
  doi: 10.1016/0006-2952(86)90774-4
  contributor:
    fullname: Marquez
– volume: 80
  start-page: 971
  year: 2012
  ident: 49
  article-title: Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L
  publication-title: Chem Biol Drug Des
  doi: 10.1111/cbdd.12050
  contributor:
    fullname: Wigle
– volume: 128
  start-page: 683
  year: 2007
  ident: 2
  article-title: The epigenomics of cancer
  publication-title: Cell
  doi: 10.1016/j.cell.2007.01.029
  contributor:
    fullname: Baylin
– volume: 25
  start-page: 1345
  year: 2011
  ident: 7
  article-title: The diverse functions of Dot1 and H3K79 methylation
  publication-title: Genes Dev
  doi: 10.1101/gad.2057811
  contributor:
    fullname: Zhang
– volume: 27
  start-page: 1160
  year: 2009
  ident: 22
  article-title: Supervised risk predictor of breast cancer based on intrinsic subtypes
  publication-title: J Clin Oncol
  doi: 10.1200/JCO.2008.18.1370
  contributor:
    fullname: Vickery
– volume: 21
  start-page: 1370
  year: 2011
  ident: 42
  article-title: Essential role of DOT1L in maintaining normal adult hematopoiesis
  publication-title: Cell Res
  doi: 10.1038/cr.2011.115
  contributor:
    fullname: Zhang
– volume: 133
  start-page: 704
  year: 2008
  ident: 29
  article-title: The epithelial-mesenchymal transition generates cells with properties of stem cells
  publication-title: Cell
  doi: 10.1016/j.cell.2008.03.027
  contributor:
    fullname: Zhou
– volume: 28
  start-page: 2825
  year: 2008
  ident: 6
  article-title: DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.02076-07
  contributor:
    fullname: Zhuo
– volume: 7
  start-page: e1000249
  year: 2009
  ident: 10
  article-title: Misguided transcriptional elongation causes mixed lineage leukemia
  publication-title: PLoS Biol
  doi: 10.1371/journal.pbio.1000249
  contributor:
    fullname: Slany
– volume: 39
  start-page: 237
  year: 2007
  ident: 48
  article-title: A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing
  publication-title: Nat Genet
  doi: 10.1038/ng1972
  contributor:
    fullname: Cope
– volume: 8
  start-page: 724
  year: 2009
  ident: 4
  article-title: Protein methyltransferases as a target class for drug discovery
  publication-title: Nat Rev Drug Discov
  doi: 10.1038/nrd2974
  contributor:
    fullname: Richon
– volume: 116
  start-page: 4483
  year: 2010
  ident: 43
  article-title: Early mammalian erythropoiesis requires the Dot1L methyltransferase
  publication-title: Blood
  doi: 10.1182/blood-2010-03-276501
  contributor:
    fullname: ZhangM, Jacob
– volume: 106
  start-page: 13820
  year: 2009
  ident: 31
  article-title: Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0905718106
  contributor:
    fullname: Sjolund
– volume: 15
  start-page: 253
  year: 2010
  ident: 30
  article-title: Epithelial-mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer
  publication-title: J Mammary Gland Biol Neoplasia
  doi: 10.1007/s10911-010-9173-1
  contributor:
    fullname: Rosen
– volume: 1
  start-page: 555
  year: 2007
  ident: 26
  article-title: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2007.08.014
  contributor:
    fullname: Brown
– volume: 20
  start-page: 53
  year: 2011
  ident: 16
  article-title: Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2011.06.009
  contributor:
    fullname: Boriack-Sjodin
– volume: 46
  start-page: 1063
  year: 1986
  ident: 37
  article-title: Biochemical mode of cytotoxic action of neplanocin A in L1210 leukemic cells
  publication-title: Cancer Res
  contributor:
    fullname: Sakurai
– volume: 32
  start-page: 1442
  year: 1989
  ident: 51
  article-title: Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities
  publication-title: J Med Chem
  doi: 10.1021/jm00127a007
  contributor:
    fullname: McPherson
– volume: 4
  start-page: 2532
  year: 2013
  ident: 46
  article-title: The polycomb group protein EZH2 is a novel therapeutic target in tongue cancer
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.1503
  contributor:
    fullname: Cheng
– volume: 8
  start-page: 890
  year: 2012
  ident: 40
  article-title: A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells
  publication-title: Nat Chem Biol
  doi: 10.1038/nchembio.1084
  contributor:
    fullname: Klaus
– volume: 14
  start-page: 1008
  year: 2007
  ident: 3
  article-title: Covalent modifications of histones during development and disease pathogenesis
  publication-title: Nat Struct Mol Biol
  doi: 10.1038/nsmb1337
  contributor:
    fullname: Shilatifard
– volume: 647
  start-page: 21
  year: 2008
  ident: 45
  article-title: Roles of the EZH2 histone methyltransferase in cancer epigenetics
  publication-title: Mutat Res
  doi: 10.1016/j.mrfmmm.2008.07.010
  contributor:
    fullname: Lange
– volume: 128
  start-page: 693
  year: 2007
  ident: 1
  article-title: Chromatin modifications and their function
  publication-title: Cell
  doi: 10.1016/j.cell.2007.02.005
  contributor:
    fullname: Kouzarides
– volume: 6
  start-page: 239
  year: 2009
  ident: 21
  article-title: The UCSC Cancer Genomics Browser
  publication-title: Nat Methods
  doi: 10.1038/nmeth0409-239
  contributor:
    fullname: Kuhn
– volume: 100
  start-page: 3983
  year: 2003
  ident: 25
  article-title: Prospective identification of tumorigenic breast cancer cells
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0530291100
  contributor:
    fullname: Clarke
– volume: 12
  start-page: 1052
  year: 2002
  ident: 8
  article-title: Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain
  publication-title: Curr Biol
  doi: 10.1016/S0960-9822(02)00901-6
  contributor:
    fullname: Struhl
– volume: 110
  start-page: 4445
  year: 2007
  ident: 9
  article-title: A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification
  publication-title: Blood
  doi: 10.1182/blood-2007-05-090514
  contributor:
    fullname: Sreekumar
– volume: 287
  start-page: 5588
  year: 2012
  ident: 20
  article-title: Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M111.328138
  contributor:
    fullname: Kim
– volume: 121
  start-page: 167
  year: 2005
  ident: 14
  article-title: hDOT1L links histone methylation to leukemogenesis
  publication-title: Cell
  doi: 10.1016/j.cell.2005.02.020
  contributor:
    fullname: Coffield
– volume: 100
  start-page: 11606
  year: 2003
  ident: 44
  article-title: EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1933744100
  contributor:
    fullname: Tomlins
– volume: 439
  start-page: 871
  year: 2006
  ident: 47
  article-title: The Polycomb group protein EZH2 directly controls DNA methylation
  publication-title: Nature
  doi: 10.1038/nature04431
  contributor:
    fullname: Didelot
– volume: 133
  start-page: 16746
  year: 2011
  ident: 34
  article-title: Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies
  publication-title: J Am Chem Soc
  doi: 10.1021/ja206312b
  contributor:
    fullname: Anglin
– volume: 21
  start-page: 1050
  year: 2007
  ident: 38
  article-title: Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells
  publication-title: Genes Dev
  doi: 10.1101/gad.1524107
  contributor:
    fullname: Lee
– volume: 127
  start-page: 109
  year: 2011
  ident: 39
  article-title: S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER2 inhibition
  publication-title: Breast Cancer Res Treat
  doi: 10.1007/s10549-010-0982-0
  contributor:
    fullname: Crabb
– volume: 971
  start-page: 38
  year: 1988
  ident: 36
  article-title: S-adenosylmethionine metabolism in HL-60 cells: effect of cell cycle and differentiation
  publication-title: Biochim Biophys Acta
  contributor:
    fullname: Kaiser
– volume: 78
  start-page: 199
  year: 2011
  ident: 35
  article-title: Chemogenetic analysis of human protein methyltransferases
  publication-title: Chem Biol Drug Des
  doi: 10.1111/j.1747-0285.2011.01135.x
  contributor:
    fullname: Elliston
– volume: 63
  start-page: 9836
  year: 2007
  ident: 50
  article-title: Synthesis of (−)-neplanocin A with the highest overall yield via an efficient Mitsunobu coupling
  publication-title: Tetrahedron
  doi: 10.1016/j.tet.2007.06.100
  contributor:
    fullname: Strazewski
– volume: 55
  start-page: 8066
  year: 2012
  ident: 17
  article-title: Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L
  publication-title: J Med Chem
  doi: 10.1021/jm300917h
  contributor:
    fullname: Jiang
– volume: 14
  start-page: 355
  year: 2008
  ident: 15
  article-title: H3K79 methylation profiles define murine and human MLL-AF4 leukemias
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2008.10.001
  contributor:
    fullname: Sinha
– volume: 37
  start-page: 429
  year: 2010
  ident: 13
  article-title: AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2010.01.026
  contributor:
    fullname: Florens
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Snippet Histone lysine methylation regulates gene expression and cancer initiation. Bioinformatics analysis suggested that DOT1L, a histone H3-lysine79 (H3K79)...
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StartPage 10665
SubjectTerms Adenosine - analogs & derivatives
Adenosine - pharmacology
Animals
Apoptosis - drug effects
Blotting, Western
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Cycle - drug effects
Cell Differentiation - drug effects
Cell Movement - drug effects
Cell Proliferation - drug effects
DNA Methylation
Enzyme Inhibitors - pharmacology
Female
Flow Cytometry
Histones - chemistry
Histones - genetics
Histones - metabolism
Humans
Immunoenzyme Techniques
Lysine
Methyltransferases - antagonists & inhibitors
Methyltransferases - genetics
Methyltransferases - metabolism
Mice
Mice, Nude
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Real-Time Polymerase Chain Reaction
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Title Inhibition of histone H3K79 methylation selectively inhibits proliferation, self-renewal and metastatic potential of breast cancer
URI https://www.ncbi.nlm.nih.gov/pubmed/25359765
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