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Science 10 August 2001:
Vol. 293. no. 5532, pp. 1068 - 1070
DOI: 10.1126/science.1063852
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The Role of DNA Methylation in Mammalian Epigenetics

Peter A. Jones,* Daiya Takai

Genes constitute only a small proportion of the total mammalian genome, and the precise control of their expression in the presence of an overwhelming background of noncoding DNA presents a substantial problem for their regulation. Noncoding DNA, containing introns, repetitive elements, and potentially active transposable elements, requires effective mechanisms for its long-term silencing. Mammals appear to have taken advantage of the possibilities afforded by cytosine methylation to provide a heritable mechanism for altering DNA-protein interactions to assist in such silencing. Genes can be transcribed from methylation-free promoters even though adjacent transcribed and nontranscribed regions are extensively methylated. Gene promoters can be used and regulated while keeping noncoding DNA, including transposable elements, suppressed. Methylation is also used for long-term epigenetic silencing of X-linked and imprinted genes and can either increase or decrease the level of transcription, depending on whether the methylation inactivates a positive or negative regulatory element.

USC/Norris Comprehensive Cancer Center, Departments of Biochemistry and Molecular Biology, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, CA 90089-9181, USA.
*   To whom correspondence should be addressed. E-mail: jones_p{at}ccnt.hsc.usc.edu

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Selection on Human Genes as Revealed by Comparisons to Chimpanzee cDNA.
I. Hellmann, S. Zollner, W. Enard, I. Ebersberger, B. Nickel, and S. Paabo (2003)
Genome Res. 13, 831-837
   Abstract »    Full Text »    PDF »
Fidelity of the Methylation Pattern and Its Variation in the Genome.
T. Ushijima, N. Watanabe, E. Okochi, A. Kaneda, T. Sugimura, and K. Miyamoto (2003)
Genome Res. 13, 868-874
   Abstract »    Full Text »    PDF »
Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus.
S. Tajima, M. Tsukamoto, and Y. Aida (2003)
J. Virol. 77, 4423-4430
   Abstract »    Full Text »    PDF »
The chicken {beta}-globin insulator element conveys chromatin boundary activity but not imprinting at the mouse Igf2/H19 domain.
P. E. Szabo, S.-H. E. Tang, M. R. Reed, F. J. Silva, W. M. K. Tsark, and J. R. Mann (2003)
Development 129, 897-904
   Abstract »    Full Text »    PDF »
Mismatch Repair in Methylated DNA. STRUCTURE AND ACTIVITY OF THE MISMATCH-SPECIFIC THYMINE GLYCOSYLASE DOMAIN OF METHYL-CpG-BINDING PROTEIN MBD4.
P. Wu, C. Qiu, A. Sohail, X. Zhang, A. S. Bhagwat, and X. Cheng (2003)
J. Biol. Chem. 278, 5285-5291
   Abstract »    Full Text »    PDF »
Bacterial CpG-DNA Aggravates Immune Complex Glomerulonephritis: Role of TLR9-Mediated Expression of Chemokines and Chemokine Receptors.
H.-J. Anders, B. Banas, Y. Linde, L. Weller, C. D. Cohen, M. Kretzler, S. Martin, V. Vielhauer, D. Schlondorff, and H.-J. Grone (2003)
J. Am. Soc. Nephrol. 14, 317-326
   Abstract »    Full Text »    PDF »
Epigenetic Regulation of a Novel Tumor Suppressor Gene (hDAB2IP) in Prostate Cancer Cell Lines.
H. Chen, S. Toyooka, A. F. Gazdar, and J.-T. Hsieh (2003)
J. Biol. Chem. 278, 3121-3130
   Abstract »    Full Text »    PDF »
DNA Methylation Maintains Allele-specific KIR Gene Expression in Human Natural Killer Cells.
H.-W. Chan, Z. B. Kurago, C. A. Stewart, M. J. Wilson, M. P. Martin, B. E. Mace, M. Carrington, J. Trowsdale, and C. T. Lutz (2003)
J. Exp. Med. 197, 245-255
   Abstract »    Full Text »    PDF »
Alternative Core Promoters Regulate Tissue-specific Transcription from the Autoimmune Diabetes-related ICA1 (ICA69) Gene Locus.
R. P. Friday, S. L. Pietropaolo, J. Profozich, M. Trucco, and M. Pietropaolo (2003)
J. Biol. Chem. 278, 853-863
   Abstract »    Full Text »    PDF »
Critical Role of Histone Methylation in Tumor Suppressor Gene Silencing in Colorectal Cancer.
Y. Kondo, L. Shen, and J.-P. J. Issa (2003)
Mol. Cell. Biol. 23, 206-215
   Abstract »    Full Text »
Inhibitors of Histone Deacetylase and DNA Methyltransferase Synergistically Activate the Methylated Metallothionein I Promoter by Activating the Transcription Factor MTF-1 and Forming an Open Chromatin Structure.
K. Ghoshal, J. Datta, S. Majumder, S. Bai, X. Dong, M. Parthun, and S. T. Jacob (2002)
Mol. Cell. Biol. 22, 8302-8319
   Abstract »    Full Text »    PDF »


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