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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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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
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Biallelic Epigenetic Inactivation of the RASSF1A Tumor Suppressor Gene in Medulloblastoma Development.
M. E. Lusher, J. C. Lindsey, F. Latif, A. D. J. Pearson, D. W. Ellison, and S. C. Clifford (2002)
Cancer Res. 62, 5906-5911
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Crucial Role of DNA Methylation in Determination of Clonally Distributed Killer Cell Ig-like Receptor Expression Patterns in NK Cells.
S. Santourlidis, H.-I. Trompeter, S. Weinhold, B. Eisermann, K. L. Meyer, P. Wernet, and M. Uhrberg (2002)
J. Immunol. 169, 4253-4261