Epigenetics, DNA methylation, and chromatin modifying drugs.
Evidence is emerging that several diseases and behavioral pathologies result from defects in gene function. The best-studied example is cancer, but other diseases such as autoimmune disease, asthma, type 2 diabetes, metabolic disorders, and autism display aberrant gene expression. Gene function may be altered by either a change in the sequence of the DNA or a change in epigenetic programming of a gene in the absence of a sequence change. With epigenetic drugs, it is possible to reverse aberrant gene expression profiles associated with different disease states. Several epigenetic drugs targeting DNA methylation and histone deacetylation enzymes have been tested in clinical trials. Understanding the epigenetic machinery and the differential roles of its components in specific disease states is essential for developing targeted epigenetic therapy.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, Montréal, Quebec H3G 1Y6, Canada. mszyf@pharma.mcgill.ca
D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects*; D004194:Disease / Q000235:genetics; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008962:Models, Theoretical; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors
D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase