Epigenetic Mechanisms

Studies reveal that when genes are no longer needed, they can be silenced by methylating the DNA and wrapping it up in a chromatin structure called a histone. When the gene is needed, this process can be reversed-the histones unravel and the DNA is available for transcription. These non-genetic-or epigenetic-mechanisms for controlling gene expression are still being discovered.

"Changes in the structure of chromatin can have profound effects on gene expression."
Epigenetic mechanisms typically work by altering the probability of gene expression, or sometimes the level of gene expression. "Changes in the structure of chromatin can have profound effects on gene expression," said David I. K. Martin, a researcher at the Victor Chang Cardiac Research Institute in Sydney, Australia. These alterations can be heritable, said Martin. A fascinating area of inquiry is the potential role of epigenetics in thalassemia disorders.

One drug that may help revive fetal hemoglobin production through epigenetic mechanisms is 5-azacitidine, a cancer drug that is capable of reactivating suppressed genes. In a clinical safety trial, 5-azacitidine boosted production of fetal hemoglobin in β-thalassemia patients, and researchers plan to go forward with a phase II trial with Decitabine, a related compound. Earlier concerns about inducing cancer with this class of drugs interrupted trials 20 years ago, but have not been realized. Now, the opposite appears to be the case, and demethylating agents may provide protection against cancer in certain settings.