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Modulation of DNA Methylation for the Treatment and Prevention of Cancer

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Cancer Chemoprevention

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Alterations in chromatin structure represent early and critical events that perturb gene expression during multistep carcinogenesis (1). The nucleosome—the basic structure of chromatin is composed of 146 basepairs of DNA coiled around an octamer of core histones (H2A, H2B, H3, and H4); nucleosomes are separated by variable lengths of linker DNA bound to histone H1 . In association with additional proteins, nucleosomes are assembled into higher order chromatin (2).The modulation of histone proteins by acetylation, phosphorylation, or methylation influences the nature and specificity of DNA-histone interactions, thus influencing gene activity (2–4). For example, deacetylation of core histone proteins by histone deacetylases (HDACs) increases DNA-histone interactions, resulting in chromatin compaction and repression of transcription, whereas acetylation of histones by histone acetyl transferases (HATs) diminishes DNA-histone binding, resulting in chromatin relaxation and enhanced gene expression (5, 6).

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  1. David S. Schrump MD
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  1. National Institutes of Health, Rockville, MD, USA

    Gary J. Kelloff MD  & Ernest T. Hawk MD, MPH  & 

  2. CCS Associates, Mountain View, CA, USA

    Caroline C. Sigman PhD

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Schrump, D.S. (2004). Modulation of DNA Methylation for the Treatment and Prevention of Cancer. In: Kelloff, G.J., Hawk, E.T., Sigman, C.C. (eds) Cancer Chemoprevention. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-767-3_42

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  • DOI: https://doi.org/10.1007/978-1-59259-767-3_42

  • Publisher Name: Humana Press, Totowa, NJ

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