Epigenetics, disease, and therapeutic interventions

Heritable changes in gene expression that do not involve coding sequence modifications are referred to as epigenetic. Epigenetic mechanisms principally include DNA methylation and a variety of histone modifications, of which the best characterized is acetylation. DNA hypermethylation and histone hypoacetylation are hallmarks of gene silencing, while DNA hypomethylation and acetylated histones promote active transcription. Aberrant DNA methylation and histone acetylation have been linked to a number of age related disorders including cancer, autoimmune disorders and others. Since epigenetic alterations are reversible, modifying epigenetic marks contributing to disease development may provide an approach to designing new therapies. Herein we review the role of epigenctic changes in disease development, and recent advances in the therapeutic modification of epigenetic marks. (c) 2006 Elsevier Ireland Ltd. All rights reserved.