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Epigenetics in human disease and prospects for epigenetic therapy

Abstract

Epigenetic mechanisms, which involve DNA and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. The study of human disease has focused on genetic mechanisms, but disruption of the balance of epigenetic networks can cause several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. The development of new diagnostic tools might reveal other diseases that are caused by epigenetic alterations. Great potential lies in the development of ‘epigenetic therapies’ — several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.

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Figure 1: Interaction between RNA, histone modification and DNA methylation in heritable silencing.
Figure 2: Mechanism of action of nucleoside analogue inhibitors.

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Acknowledgements

We thank C. Nguyen for his help with the figures, and A. Yang and J. Rice for critical reading of the manuscript. This work was supported by the National Cancer Institute and the Max Kade Foundation.

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P.A.J. is a shareholder and consultant for Epigenomics AG and a consultant for SuperGen Inc., which is developing decitabine as a cancer treatment.

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Egger, G., Liang, G., Aparicio, A. et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature 429, 457–463 (2004). https://doi.org/10.1038/nature02625

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