Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention  Cancer Health Disparities Conference 2009
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 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 McGarvey, K. M.
Right arrow Articles by Baylin, S. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McGarvey, K. M.
Right arrow Articles by Baylin, S. B.
[Cancer Research 66, 3541-3549, April 1, 2006]
© 2006 American Association for Cancer Research


Cell, Tumor, and Stem Cell Biology

Silenced Tumor Suppressor Genes Reactivated by DNA Demethylation Do Not Return to a Fully Euchromatic Chromatin State

Kelly M. McGarvey1,2, Jill A. Fahrner1,2, Eriko Greene1,2, Joost Martens3, Thomas Jenuwein3 and Stephen B. Baylin1

1 The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University; 2 The Graduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and 3 Research Institute of Molecular Pathology, The Vienna Biocenter, Vienna, Austria

Requests for reprints: Stephen B. Baylin, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Suite 541, 1650 Orleans Street, Baltimore, MD 21231. Phone: 410-955-5806; Fax: 410-614-9884; E-mail: sbaylin{at}jhmi.edu.

Histone H3 lysine 9 (H3K9) and lysine 27 (H3K27) trimethylation are properties of stably silenced heterochromatin whereas H3K9 dimethylation (H3K9me2) is important for euchromatic gene repression. In colorectal cancer cells, all of these marks, as well as the key enzymes which establish them, surround the hMLH1 promoter when it is DNA hypermethylated and aberrantly silenced, but are absent when the gene is unmethylated and fully expressed in a euchromatic state. When the aberrantly silenced gene is DNA demethylated and reexpressed following 5-aza-2'-deoxycytidine treatment, H3K9me1 and H3K9me2 are the only silencing marks that are lost. A series of other silenced and DNA hypermethylated gene promoters behave identically even when the genes are chronically DNA demethylated and reexpressed after genetic knockout of DNA methyltransferases. Our data indicate that when transcription of DNA hypermethylated genes is activated in cancer cells, their promoters remain in an environment with certain heterochromatic characteristics. This finding has important implications for the translational goal of reactivating aberrantly silenced cancer genes as a therapeutic maneuver. (Cancer Res 2006; 66(7): 3541-9)




This article has been cited by other articles:


Home page
BioinformaticsHome page
H. Xu, C.-L. Wei, F. Lin, and W.-K. Sung
An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data
Bioinformatics, October 15, 2008; 24(20): 2344 - 2349.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. M. Yi, H.-C. Tsai, S. C. Glockner, S. Lin, J. E. Ohm, H. Easwaran, C. D. James, J. F. Costello, G. Riggins, C. G. Eberhart, et al.
Abnormal DNA Methylation of CD133 in Colorectal and Glioblastoma Tumors
Cancer Res., October 1, 2008; 68(19): 8094 - 8103.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
X. Zhu, X. Mao, R. Hurren, A. D. Schimmer, S. Ezzat, and S. L. Asa
Deoxyribonucleic Acid Methyltransferase 3B Promotes Epigenetic Silencing through Histone 3 Chromatin Modifications in Pituitary Cells
J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3610 - 3617.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
K. M. McGarvey, L. Van Neste, L. Cope, J. E. Ohm, J. G. Herman, W. Van Criekinge, K. E. Schuebel, and S. B. Baylin
Defining a Chromatin Pattern that Characterizes DNA-Hypermethylated Genes in Colon Cancer Cells
Cancer Res., July 15, 2008; 68(14): 5753 - 5759.
[Abstract] [Full Text] [PDF]


Home page
Genome ResHome page
V. K. Tiwari, L. Cope, K. M. McGarvey, J. E. Ohm, and S. B. Baylin
A novel 6C assay uncovers Polycomb-mediated higher order chromatin conformations
Genome Res., July 1, 2008; 18(7): 1171 - 1179.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
A. H. Ting, H. Suzuki, L. Cope, K. E. Schuebel, B. H. Lee, M. Toyota, K. Imai, Y. Shinomura, T. Tokino, and S. B. Baylin
A Requirement for DICER to Maintain Full Promoter CpG Island Hypermethylation in Human Cancer Cells
Cancer Res., April 15, 2008; 68(8): 2570 - 2575.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
K. J. Briggs, I. M. Corcoran-Schwartz, W. Zhang, T. Harcke, W. L. Devereux, S. B. Baylin, C. G. Eberhart, and D. N. Watkins
Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma
Genes & Dev., March 15, 2008; 22(6): 770 - 785.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
M. Schnekenburger, G. Talaska, and A. Puga
Chromium Cross-Links Histone Deacetylase 1-DNA Methyltransferase 1 Complexes to Chromatin, Inhibiting Histone-Remodeling Marks Critical for Transcriptional Activation
Mol. Cell. Biol., October 15, 2007; 27(20): 7089 - 7101.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
T. Hucl, J. R. Brody, E. Gallmeier, C. A. Iacobuzio-Donahue, I. K. Farrance, and S. E. Kern
High Cancer-Specific Expression of Mesothelin (MSLN) Is Attributable to an Upstream Enhancer Containing a Transcription Enhancer Factor Dependent MCAT Motif
Cancer Res., October 1, 2007; 67(19): 9055 - 9065.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
M. P. Hitchins, V. A. Lin, A. Buckle, K. Cheong, N. Halani, S. Ku, C.-T. Kwok, D. Packham, C. M. Suter, A. Meagher, et al.
Epigenetic Inactivation of a Cluster of Genes Flanking MLH1 in Microsatellite-Unstable Colorectal Cancer
Cancer Res., October 1, 2007; 67(19): 9107 - 9116.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
V. K. Rajasekhar and M. Begemann
Concise Review: Roles of Polycomb Group Proteins in Development and Disease: A Stem Cell Perspective
Stem Cells, October 1, 2007; 25(10): 2498 - 2510.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
H. Rincon-Arano, M. Furlan-Magaril, and F. Recillas-Targa
Protection against telomeric position effects by the chicken cHS4 beta-globin insulator
PNAS, August 28, 2007; 104(35): 14044 - 14049.
[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
Cancer Res.Home page
K. M. McGarvey, E. Greene, J. A. Fahrner, T. Jenuwein, and S. B. Baylin
DNA Methylation and Complete Transcriptional Silencing of Cancer Genes Persist after Depletion of EZH2
Cancer Res., June 1, 2007; 67(11): 5097 - 5102.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
Y. Huang, E. Greene, T. Murray Stewart, A. C. Goodwin, S. B. Baylin, P. M. Woster, and R. A. Casero Jr
Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes
PNAS, May 8, 2007; 104(19): 8023 - 8028.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
X. Zhu, K. Lee, S. L. Asa, and S. Ezzat
Epigenetic Silencing through DNA and Histone Methylation of Fibroblast Growth Factor Receptor 2 in Neoplastic Pituitary Cells
Am. J. Pathol., May 1, 2007; 170(5): 1618 - 1628.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
I. A. De La Rosa-Velazquez, H. Rincon-Arano, L. Benitez-Bribiesca, and F. Recillas-Targa
Epigenetic Regulation of the Human Retinoblastoma Tumor Suppressor Gene Promoter by CTCF
Cancer Res., March 15, 2007; 67(6): 2577 - 2585.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. L. Zinn, K. Pruitt, S. Eguchi, S. B. Baylin, and J. G. Herman
hTERT Is Expressed in Cancer Cell Lines Despite Promoter DNA Methylation by Preservation of Unmethylated DNA and Active Chromatin around the Transcription Start Site
Cancer Res., January 1, 2007; 67(1): 194 - 201.
[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
GutHome page
J J L Wong, N J Hawkins, and R L Ward
Colorectal cancer: a model for epigenetic tumorigenesis
Gut, January 1, 2007; 56(1): 140 - 148.
[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
Cancer Res.Home page
H. Chen, Y. Yan, T. L. Davidson, Y. Shinkai, and M. Costa
Hypoxic Stress Induces Dimethylated Histone H3 Lysine 9 through Histone Methyltransferase G9a in Mammalian Cells.
Cancer Res., September 15, 2006; 66(18): 9009 - 9016.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
G. Foltz, G.-Y. Ryu, J.-G. Yoon, T. Nelson, J. Fahey, A. Frakes, H. Lee, L. Field, K. Zander, Z. Sibenaller, et al.
Genome-Wide Analysis of Epigenetic Silencing Identifies BEX1 and BEX2 as Candidate Tumor Suppressor Genes in Malignant Glioma.
Cancer Res., July 1, 2006; 66(13): 6665 - 6674.
[Abstract] [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 © 2006 by the American Association for Cancer Research.