New mechanism for gene silencing identified

PHILADELPHIA--Humans are estimated to have some 30,000-70,000 genes, but in any one of the body's many cell types, most of these genes are turned off, or silenced, appropriately prevented from doing their work of protein production. For example, there are thousands of genes that are active only during embryo development, their sole purpose to give rise to a perfectly formed fetus. These genes are found in every cell of the body but remain silent in healthy adults. Scientists have learned, however, that in many human cancers these genes associated with embryogenesis are inappropriately reactivated, causing the explosion of uncoordinated cell growth that is the hallmark of tumor formation.

Now, researchers at The Wistar Institute have identified a mechanism by which genes associated with embryogenesis are kept silent. Importantly, the silencing is heritable; that is, when a cell divides, its daughter cells maintain not only copies of its DNA but also the silencing of these genes involved in embryogenesis. Knowledge of this mechanism could lead to new cancer therapies aimed at re-silencing inappropriately activated genes. The research appears in tomorrow's print edition of Genes & Development and is featured on the journal's cover.

"The next great challenge for scientists studying the genome is determining how the genes in every cell of our body are regulated," says Frank J. Rauscher III, Ph.D,, professor, deputy director of the Wistar Cancer Center, and associate director of research programs at The Wistar Institute. Rauscher is senior author of the study. "We know certain genes have to be activated in skin, for example, and silenced in the heart, liver, and other organs. The concept of the so-called epigenome--that is, how genes are either activated or repressed--will be critical to furthering our understanding of cancer and other diseases."

"In this study," Rauscher continues, "we've discovered a new mechanism involving multiple enzymes that

Contact: Marion Wyce
The Wistar Institute

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