DNA MethylationPhysiology, pathology and disease

Published July 2010 Updated March 2011 11 lectures
Prof. Jean-Pierre Issa
University of Texas MD Anderson Cancer Center, USA
Summary

Methylation is the only known naturally occurring modification of DNA and plays critical roles in DNA packaging, chromosomal stability and regulation of gene expression. While it plays diverse roles in mammalian physiology, it is best known for being a mediator of epigenetics – gene expression states that are stably transmitted... read morethrough mitosis without a genetic change. The best described examples of methylation-dependent epigenetic regulation are X-inactivation in females and genetic imprinting, but the process likely plays an essential role in many other situations such as germ-cell restricted gene expression, organism development and cellular differentiation. DNA methylation has attracted much interest lately because of its potential as a mediator of dietary and environmental clues, particularly during early embryogenesis. While generally thought of as a very stable modification, subtle or major changes in DNA methylation have been observed in disease states ranging from cancer to atherosclerosis. This in turn has attracted much attention due to the potential reversibility of DNA methylation using drug intervention targeted at the enzymes essential for methylation maintenance. Indeed, two such drugs are now used worldwide for the treatment of certain forms of leukemias.