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Science 15 October 1999:
Vol. 286. no. 5439, pp. 481 - 486
DOI: 10.1126/science.286.5439.481
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Review

Epigenetics: Regulation Through Repression

Alan P. Wolffe, 1* Marjori A. Matzke 2*

Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic phenomena have major economic and medical relevance, and several, such as imprinting and paramutation, violate Mendelian principles. Recent discoveries link the recognition of nucleic acid sequence homology to the targeting of DNA methylation, chromosome remodeling, and RNA turnover. Although epigenetic mechanisms help to protect cells from parasitic elements, this defense can complicate the genetic manipulation of plants and animals. Essential for normal development, epigenetic controls become misdirected in cancer cells and other human disease syndromes.

1 Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892-5431, USA.
2 Austrian Academy of Sciences, Institute of Molecular Biology, Billrothstrasse 11, A-5020 Salzburg, Austria.
*   To whom correspondence should be addressed: E-mail: awlme{at}helix.nih.gov (A.P.W.) and amatzke{at}server1.imolbio.oeaw.ac.at (M.A.M.)

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S. Friso, S.-W. Choi, D. Girelli, J. B. Mason, G. G. Dolnikowski, P. J. Bagley, O. Olivieri, P. F. Jacques, I. H. Rosenberg, R. Corrocher, et al. (2002)
PNAS 99, 5606-5611
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Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems.
N. J. Caplen, S. Parrish, F. Imani, A. Fire, and R. A. Morgan (2001)
PNAS 98, 9742-9747
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Fertile Hypomorphic ARGONAUTE (ago1) Mutants Impaired in Post-Transcriptional Gene Silencing and Virus Resistance.
J.-B. Morel, C. Godon, P. Mourrain, C. Beclin, S. Boutet, F. Feuerbach, F. Proux, and H. Vaucheret (2002)
PLANT CELL 14, 629-639
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Myocardial Fibrosis in Chronic Aortic Regurgitation: Molecular and Cellular Responses to Volume Overload.
J. S. Borer, S. Truter, E. M. Herrold, D. J. Falcone, M. Pena, J. N. Carter, T. F. Dumlao, J. A. Lee, and P. G. Supino (2002)
Circulation 105, 1837-1842
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Science. ISSN 0036-8075 (print), 1095-9203 (online)