Epigenetics: the role of methylation in the mechanism of action of tumor suppressor genes.
Epigenetics is the study of mitotically heritable changes in gene expression without any changes in the primary DNA sequence. The major step in epigenetic gene regulation is gene inactivation by hypermethylation of CpG islands located in the promoter region. Specific enzymes and methylated DNA binding proteins play a major role in causing reduced expression of tumor suppressor genes, resulting in tumor formation and its progression. Prevention approaches are needed to avoid tumor formation. One approach to inhibiting inactivation of tumor suppressor genes is to use chemical agents such as 5-azacytidine to prevent hypermethylation of DNA. Increased understanding of the mechanism of epigenetic silencing and the identification of additional molecular mechanisms (e.g., histone methylases) that may be targeted by pharmaceutical interventions may lead to more preventive strategies. The current status of the epigenetic regulation of tumor suppressor genes is discussed in this review article.
Jain
Pawan K
PK
DETTD, OBRR, CBER, Food and Drug Administration, Rockville, Maryland 20852, USA. jain@cbr.fda.gov
D019175:DNA Methylation; D016147:Genes, Tumor Suppressor; D006655:Histone Deacetylases / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011496:Protein Methyltransferases
D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases