Factors influencing epigenetic mechanisms and related diseases.

It is becoming clear that epigenetic mechanisms are associated with disease. To date, a myriad of epigenetic alterations, including altered DNA methylation and aberrant histone post-translational modifications, have been linked with various conditions. The most widely investigated example is the link between aberrant DNA methylation and malignancy that has lead to the clinical use of the DNA methyltransferase inhibitors, azacitidine and decitabine, for the treatment of myelodysplastic syndromes. Similarly, defective histone acetylation status has been associated with malignancy, providing the basis for the clinical use of the histone deacetylase inhibitors suberoylanilide hydroxamic acid and depsipeptide for the treatment of cutaneous T-cell lymphoma. In addition, there is an emerging association between perturbed fetal epigenetic programming and developmental origins of disease due to both nutritional and environmental factors. In particular, epigenetic events associated with metabolic syndrome have been identified. Related epigenetic mechanisms as well potential pharmacological and dietary interventions at critical periods of development form a large part of the discussion in this Forum. Further, this Forum provides an in-depth account of the association between epigenetic mechanisms and carcinogenesis with a focus on disease prevention with dietary chromatin-modifying compounds. Finally, the association between aberrant epigenetic events and neurodegenerative conditions, such as Alzheimer's disease (AD), is becoming apparent. A research article in this Forum identifies a potential new polymorphism associated with one-carbon metabolism that may contribute to the pathogenesis of AD. Overall, this Forum provides a detailed account of known epigenetic processes in developmental programming and human disease.