Cancer Research Cancer Medicine 8 2010 Workshops
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nguyen, C. T.
Right arrow Articles by Jones, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nguyen, C. T.
Right arrow Articles by Jones, P. A.
[Cancer Research 62, 6456-6461, November 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Histone H3-Lysine 9 Methylation Is Associated with Aberrant Gene Silencing in Cancer Cells and Is Rapidly Reversed by 5-Aza-2'-deoxycytidine1

Carvell T. Nguyen, Daniel J. Weisenberger, Mihaela Velicescu, Felicidad A. Gonzales, Joy C. Y. Lin, Gangning Liang and Peter A. Jones2

Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center and Hospital, University of Southern California, Keck School of Medicine, Los Angeles, California 90089

Epigenetic modifications of cytosine residues in DNA and the amino termini of histone proteins have emerged as key mechanisms in chromatin remodeling, impacting both the transcriptional regulation and the establishment of chromosomal domains. Using the chromatin immunoprecipitation (ChIP) assay, we demonstrate that aberrantly silenced genes in cancer cells exhibit a heterochromatic structure that is characterized by histone H3 lysine 9 (H3-K9) hypermethylation and histone H3 lysine 4 (H3-K4) hypomethylation. This aberrant heterochromatin is incompatible with transcriptional initiation but does not inhibit elongation by RNA polymerase II. H3-K9 methylation may, therefore, play a role in the silencing of tumor-suppressor genes in cancer. Treatment with 5-aza-2'-deoxycytidine (5-Aza-CdR), previously known for its ability to inhibit cytosine methylation, induced a rapid and substantial remodeling of the heterochromatic domains of the p14ARF/p16INK4a locus in T24 bladder cancer cells, reducing levels of dimethylated H3-K9 and increasing levels of dimethylated H3-K4 at this locus. In addition, 5-Aza-CdR increased acetylation and H3-K4 methylation at the unmethylated p14 promoter, suggesting it can induce chromatin remodeling independently of its effects on cytosine methylation.




This article has been cited by other articles:


Home page
 CarcinogenesisHome page
S. Sharma, T. K. Kelly, and P. A. Jones
Epigenetics in cancer
Carcinogenesis, January 1, 2010; 31(1): 27 - 36.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Q. Li, D. L. Bartlett, M. C. Gorry, M. E. O'Malley, and Z. S. Guo
Three Epigenetic Drugs Up-Regulate Homeobox Gene Rhox5 in Cancer Cells through Overlapping and Distinct Molecular Mechanisms
Mol. Pharmacol., November 1, 2009; 76(5): 1072 - 1081.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Jeong, G. Liang, S. Sharma, J. C. Lin, S. H. Choi, H. Han, C. B. Yoo, G. Egger, A. S. Yang, and P. A. Jones
Selective Anchoring of DNA Methyltransferases 3A and 3B to Nucleosomes Containing Methylated DNA
Mol. Cell. Biol., October 1, 2009; 29(19): 5366 - 5376.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Hirata, Y. Hinoda, K. Nakajima, K. Kawamoto, N. Kikuno, K. Kawakami, S. Yamamura, K. Ueno, S. Majid, S. Saini, et al.
Wnt Antagonist Gene DKK2 Is Epigenetically Silenced and Inhibits Renal Cancer Progression through Apoptotic and Cell Cycle Pathways
Clin. Cancer Res., September 15, 2009; 15(18): 5678 - 5687.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
K. Yamakoshi, A. Takahashi, F. Hirota, R. Nakayama, N. Ishimaru, Y. Kubo, D. J. Mann, M. Ohmura, A. Hirao, H. Saya, et al.
Real-time in vivo imaging of p16Ink4a reveals cross talk with p53
J. Cell Biol., August 10, 2009; 186(3): 393 - 407.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. P. Mohammad, Y. Cai, K. M. McGarvey, H. Easwaran, L. Van Neste, J. E. Ohm, H. M. O'Hagan, and S. B. Baylin
Polycomb CBX7 Promotes Initiation of Heritable Repression of Genes Frequently Silenced with Cancer-Specific DNA Hypermethylation
Cancer Res., August 1, 2009; 69(15): 6322 - 6330.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. T. McCabe, J. C. Brandes, and P. M. Vertino
Cancer DNA Methylation: Molecular Mechanisms and Clinical Implications
Clin. Cancer Res., June 15, 2009; 15(12): 3927 - 3937.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Shikauchi, A. Saiura, T. Kubo, Y. Niwa, J. Yamamoto, Y. Murase, and H. Yoshikawa
SALL3 Interacts with DNMT3A and Shows the Ability To Inhibit CpG Island Methylation in Hepatocellular Carcinoma
Mol. Cell. Biol., April 1, 2009; 29(7): 1944 - 1958.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Hambach, K.-W. Ling, J. Pool, Z. Aghai, E. Blokland, H. J. Tanke, J. A. Bruijn, H. Halfwerk, H. van Boven, B. Wieles, et al.
Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy
Blood, March 19, 2009; 113(12): 2715 - 2722.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. K. Kim, P.-O. Esteve, S. E. Jacobsen, and S. Pradhan
UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells
Nucleic Acids Res., February 1, 2009; 37(2): 493 - 505.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Kapoor-Vazirani, J. D. Kagey, D. R. Powell, and P. M. Vertino
Role of hMOF-Dependent Histone H4 Lysine 16 Acetylation in the Maintenance of TMS1/ASC Gene Activity
Cancer Res., August 15, 2008; 68(16): 6810 - 6821.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Yamada, Y. Nishida, H. Tsutsumida, T. Hamada, M. Goto, M. Higashi, M. Nomoto, and S. Yonezawa
MUC1 Expression Is Regulated by DNA Methylation and Histone H3 Lysine 9 Modification in Cancer Cells
Cancer Res., April 15, 2008; 68(8): 2708 - 2716.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. A. Hinshelwood, L. I. Huschtscha, J. Melki, C. Stirzaker, A. Abdipranoto, B. Vissel, T. Ravasi, C. A. Wells, D. A. Hume, R. R. Reddel, et al.
Concordant Epigenetic Silencing of Transforming Growth Factor- Signaling Pathway Genes Occurs Early in Breast Carcinogenesis
Cancer Res., December 15, 2007; 67(24): 11517 - 11527.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. Watanabe, M. Toyota, Y. Kondo, H. Suzuki, T. Imai, M. Ohe-Toyota, R. Maruyama, M. Nojima, Y. Sasaki, Y. Sekido, et al.
PRDM5 Identified as a Target of Epigenetic Silencing in Colorectal and Gastric Cancer
Clin. Cancer Res., August 15, 2007; 13(16): 4786 - 4794.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
F. V. Jacinto and M. Esteller
Mutator pathways unleashed by epigenetic silencing in human cancer
Mutagenesis, July 1, 2007; 22(4): 247 - 253.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
A. Smallwood, P.-O. Esteve, S. Pradhan, and M. Carey
Functional cooperation between HP1 and DNMT1 mediates gene silencing
Genes & Dev., May 15, 2007; 21(10): 1169 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. M.E.I. Hellebrekers, V. Melotte, E. Vire, E. Langenkamp, G. Molema, F. Fuks, J. G. Herman, W. Van Criekinge, A. W. Griffioen, and M. van Engeland
Identification of Epigenetically Silenced Genes in Tumor Endothelial Cells
Cancer Res., May 1, 2007; 67(9): 4138 - 4148.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
M. Hummel, S. Yan, Z. Li, T. K. Varghese, and M. Abecassis
Transcriptional reactivation of murine cytomegalovirus ie gene expression by 5-aza-2'-deoxycytidine and trichostatin A in latently infected cells despite lack of methylation of the major immediate-early promoter
J. Gen. Virol., April 1, 2007; 88(4): 1097 - 1102.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
T. Ripperger, N. von Neuhoff, K. Kamphues, M. Emura, U. Lehmann, M. Tauscher, M. Schraders, P. Groenen, B. Skawran, C. Rudolph, et al.
Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle cell lymphomas
Haematologica, April 1, 2007; 92(4): 460 - 468.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
G. Strathdee, A. Sim, R. Soutar, T. L. Holyoake, and R. Brown
HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia
Carcinogenesis, February 1, 2007; 28(2): 299 - 309.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Egger, A. M. Aparicio, S. G. Escobar, and P. A. Jones
Inhibition of Histone Deacetylation Does Not Block Resilencing of p16 after 5-Aza-2'-Deoxycytidine Treatment
Cancer Res., January 1, 2007; 67(1): 346 - 353.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
R. Claus, M. Fliegauf, M. Stock, J. A. Duque, M. Kolanczyk, and M. Lubbert
Inhibitors of DNA methylation and histone deacetylation independently relieve AML1/ETO-mediated lysozyme repression
J. Leukoc. Biol., December 1, 2006; 80(6): 1462 - 1472.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
A. H. Ting, K. M. McGarvey, and S. B. Baylin
The cancer epigenome--components and functional correlates
Genes & Dev., December 1, 2006; 20(23): 3215 - 3231.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. K. W. To, Z. Zhan, and S. E. Bates
Aberrant Promoter Methylation of the ABCG2 Gene in Renal Carcinoma
Mol. Cell. Biol., November 15, 2006; 26(22): 8572 - 8585.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. M.E.I. Hellebrekers, K. Castermans, E. Vire, R. P.M. Dings, N. T.H. Hoebers, K. H. Mayo, M. G.A. oude Egbrink, G. Molema, F. Fuks, M. van Engeland, et al.
Epigenetic Regulation of Tumor Endothelial Cell Anergy: Silencing of Intercellular Adhesion Molecule-1 by Histone Modifications.
Cancer Res., November 15, 2006; 66(22): 10770 - 10777.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
N. Nikolettos, B. Asimakopoulos, and I. S. Papastefanou
Intracytoplasmic Sperm Injection-An Assisted Reproduction Technique That Should Make Us Cautious About Imprinting Deregulation
Reproductive Sciences, July 1, 2006; 13(5): 317 - 328.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
S. D. Gore, S. Baylin, E. Sugar, H. Carraway, C. B. Miller, M. Carducci, M. Grever, O. Galm, T. Dauses, J. E. Karp, et al.
Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms.
Cancer Res., June 15, 2006; 66(12): 6361 - 6369.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. H. Abbosh, J. S. Montgomery, J. A. Starkey, M. Novotny, E. G. Zuhowski, M. J. Egorin, A. P. Moseman, A. Golas, K. M. Brannon, C. Balch, et al.
Dominant-Negative Histone H3 Lysine 27 Mutant Derepresses Silenced Tumor Suppressor Genes and Reverses the Drug-Resistant Phenotype in Cancer Cells
Cancer Res., June 1, 2006; 66(11): 5582 - 5591.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. M. McGarvey, J. A. Fahrner, E. Greene, J. Martens, T. Jenuwein, and S. B. Baylin
Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state.
Cancer Res., April 1, 2006; 66(7): 3541 - 3549.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
M. S. WEINBERG, L. M. VILLENEUVE, A. EHSANI, M. AMARZGUIOUI, L. AAGAARD, Z.-X. CHEN, A. D. RIGGS, J. J. ROSSI, and K. V. MORRIS
The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells
RNA, February 1, 2006; 12(2): 256 - 262.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
I. Hernandez-Munoz, P. Taghavi, C. Kuijl, J. Neefjes, and M. van Lohuizen
Association of BMI1 with Polycomb Bodies Is Dynamic and Requires PRC2/EZH2 and the Maintenance DNA Methyltransferase DNMT1
Mol. Cell. Biol., December 15, 2005; 25(24): 11047 - 11058.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. Fatemi, M. M. Pao, S. Jeong, E. N. Gal-Yam, G. Egger, D. J. Weisenberger, and P. A. Jones
Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level
Nucleic Acids Res., November 27, 2005; 33(20): e176 - e176.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Zhang, N. Fatima, and M. L. Dufau
Coordinated Changes in DNA Methylation and Histone Modifications Regulate Silencing/Derepression of Luteinizing Hormone Receptor Gene Transcription
Mol. Cell. Biol., September 15, 2005; 25(18): 7929 - 7939.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
Q. Zhang, J. N. Rubenstein, T. L. Jang, M. Pins, B. Javonovic, X. Yang, S.-J. Kim, I. Park, and C. Lee
Insensitivity to Transforming Growth Factor-{beta} Results from Promoter Methylation of Cognate Receptors in Human Prostate Cancer Cells (LNCaP)
Mol. Endocrinol., September 1, 2005; 19(9): 2390 - 2399.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Fan, E.-i. Kodama, Y. Koh, M. Nakao, and M. Matsuoka
Halogenated Thymidine Analogues Restore the Expression of Silenced Genes without Demethylation
Cancer Res., August 1, 2005; 65(15): 6927 - 6933.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
K. N. Bhalla
Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies
J. Clin. Oncol., June 10, 2005; 23(17): 3971 - 3993.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
A. M. Bode and Z. Dong
Inducible Covalent Posttranslational Modification of Histone H3
Sci. Signal., April 26, 2005; 2005(281): re4 - re4.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. W. Laird
Cancer epigenetics
Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R65 - R76.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S.-i. Kumakura, T. W. Tsutsui, J. Yagisawa, J. C. Barrett, and T. Tsutsui
Reversible Conversion of Immortal Human Cells from Telomerase-Positive to Telomerase-Negative Cells
Cancer Res., April 1, 2005; 65(7): 2778 - 2786.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. D. Edberg, J. N. Adkins, D. L. Springer, and R. Reeves
Dynamic and Differential in Vivo Modifications of the Isoform HMGA1a and HMGA1b Chromatin Proteins
J. Biol. Chem., March 11, 2005; 280(10): 8961 - 8973.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
W. Zhao, H. Soejima, K. Higashimoto, T. Nakagawachi, T. Urano, S. Kudo, S. Matsukura, S. Matsuo, K. Joh, and T. Mukai
The Essential Role of Histone H3 Lys9 Di-Methylation and MeCP2 Binding in MGMT Silencing with Poor DNA Methylation of the Promoter CpG Island
J. Biochem., March 1, 2005; 137(3): 431 - 440.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P.-O. Esteve, H. G. Chin, and S. Pradhan
Human maintenance DNA (cytosine-5)-methyltransferase and p53 modulate expression of p53-repressed promoters
PNAS, January 25, 2005; 102(4): 1000 - 1005.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
S.B. BAYLIN and W.Y. CHEN
Aberrant Gene Silencing in Tumor Progression: Implications for Control of Cancer
Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 427 - 433.
[Abstract] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Liang, J. C. Y. Lin, V. Wei, C. Yoo, J. C. Cheng, C. T. Nguyen, D. J. Weisenberger, G. Egger, D. Takai, F. A. Gonzales, et al.
Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome
PNAS, May 11, 2004; 101(19): 7357 - 7362.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Kondo, L. Shen, P. S. Yan, T. H.-M. Huang, and J.-P. J. Issa
Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation
PNAS, May 11, 2004; 101(19): 7398 - 7403.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. J. Rush, A. Raval, P. Funchain, A. J. Johnson, L. Smith, D. M. Lucas, M. Bembea, T.-H. Liu, N. A. Heerema, L. Rassenti, et al.
Epigenetic Profiling in Chronic Lymphocytic Leukemia Reveals Novel Methylation Targets
Cancer Res., April 1, 2004; 64(7): 2424 - 2433.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. P. Kimura, S. A. Liebhaber, and N. E. Cooke
Epigenetic Modifications at the Human Growth Hormone Locus Predict Distinct Roles for Histone Acetylation and Methylation in Placental Gene Activation
Mol. Endocrinol., April 1, 2004; 18(4): 1018 - 1032.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. C. Cheng, D. J. Weisenberger, F. A. Gonzales, G. Liang, G.-L. Xu, Y.-G. Hu, V. E. Marquez, and P. A. Jones
Continuous Zebularine Treatment Effectively Sustains Demethylation in Human Bladder Cancer Cells
Mol. Cell. Biol., February 1, 2004; 24(3): 1270 - 1278.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Q. Yan, E. Cho, S. Lockett, and K. Muegge
Association of Lsh, a Regulator of DNA Methylation, with Pericentromeric Heterochromatin Is Dependent on Intact Heterochromatin
Mol. Cell. Biol., December 1, 2003; 23(23): 8416 - 8428.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. G. Herman and S. B. Baylin
Gene Silencing in Cancer in Association with Promoter Hypermethylation
N. Engl. J. Med., November 20, 2003; 349(21): 2042 - 2054.
[Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Siddiqui, D. A. Solomon, R. W. Gunawardena, Y. Wang, and E. S. Knudsen
Histone Deacetylation of RB-Responsive Promoters: Requisite for Specific Gene Repression but Dispensable for Cell Cycle Inhibition
Mol. Cell. Biol., November 1, 2003; 23(21): 7719 - 7731.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
J. A. Fahrner and S. B. Baylin
Heterochromatin: stable and unstable invasions at home and abroad
Genes & Dev., August 1, 2003; 17(15): 1805 - 1812.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Kondo and J.-P. J. Issa
Enrichment for Histone H3 Lysine 9 Methylation at Alu Repeats in Human Cells
J. Biol. Chem., July 18, 2003; 278(30): 27658 - 27662.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Lachner, R. J. O'Sullivan, and T. Jenuwein
An epigenetic road map for histone lysine methylation
J. Cell Sci., June 1, 2003; 116(11): 2117 - 2124.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.