PHILADELPHIA - Although the human genome is estimated to contain about 35,000 genes, only a fraction of these genes are turned on in a given cell type under normal circumstances. Precise control of gene expression is essential; many cancers have been linked to the improper activation of genes that should remain repressed, or silenced.
Now, researchers at The Wistar Institute report the identification of a new enzyme that is required for the silencing of certain genes. The enzyme functions by placing a molecular marker on a gene that causes the gene to be silenced. When this molecular marker is lost, certain genes may be improperly reactivated, which can result in cancer. Discovery of the enzyme could lead to new cancer therapies. A report on the research appears in the April 15 issue of Genes and Development.
"In this study we showed that when this enzyme is active at a particular gene, it places a molecular marker on the gene," says Frank J. Rauscher III, Ph.D., a professor at The Wistar Institute and deputy director of The Wistar Institute Cancer Center. "This molecular marker is crucial in silencing sets of genes."
The molecular marker is the methylation, or addition of a methyl group, to the DNA packaging proteins called histones on the gene that is to be silenced. When this molecular marker is lost, certain genes are no longer silenced but are instead reactivated, which may result in cancer. For instance, Rauscher notes that it has recently been shown that when you lose this molecular marker on a particular set of genes, a normally nonaggressive breast cancer can become very aggressive and metastatic.
"Now that we have found a new enzyme that is required for the silencing of certain genes," Rauscher says, "we believe it will be possible to create specific drugs that can either repress or activate gene expression through the targeting of this enzyme. This could lead to therapies for cancer, specifically for controlling the met
Contact: Marion Wyce
The Wistar Institute