The Reporter: June 1996, Vol.7, No.3
Research Notes
Genomic Methylation

Researchers have taken the first steps in developing therapies for AIDS and cancer that rely on a naturally occurring defense system within cells. That system, based on methylation of cytosines in DNA, is being used to inactivate deleterious genes. In an April issue of Nature Genetics, Dr. Timothy Bestor, P&S associate professor of genetics and development, discussed the possible biological roles of genomic methylation patterns.

Methylation is a process in which methyl groups are attached to cytosine residues in DNA, shutting off the expression of a gene. Although the exact function of the process is not entirely clear, one possibility is that methylation turns genes on and off during an organism's development. In addition, methylation may act as a genomic defense system by restricting the transcription of parasitic sequence elements-stretches of DNA that have been incorporated into the genome from either outside sources or transcription errors and that are potentially harmful if activated.

Without the methylation defense system, the sequence elements would proliferate unchecked and might impose a lethal mutagenic or cytotoxic burden, says Dr. Bestor.

Dr. Bestor cloned and sequenced mammalian DNA methyltransferase and used gene disruption techniques to show that DNA methyltransferase protein is required for mammalian development. Furthermore, in preliminary work with targeted methylation, Dr. Bestor; Dr. Guo-Liang Xu, a postdoctoral fellow; and Michael Livstone, a graduate student, are developing CpG-specific DNA methyltransferase of novel sequence specificity that can be directed to a single promoter that controls the expression of viral DNA or other deleterious genes.

If the technology can be further developed and harnessed, it holds great promise for reducing the severity and incidence of a number of diseases-such as AIDS, hepatitis B, and human papilloma virus infection-by shutting off the genes that are involved in specific diseases, says Dr. Bestor.