In cancer, an embryonic gene-silencing mechanism gone awry

The researchers identified a group of proteins that play a key role in this phenomenon. They bind to a DNA sequence near the gene, and substitute one DNA element for another, essentially "marking" the sequence. This phenomenon is known as "methylation." Once the marker is in place, the cellular machinery recognizes the sign and maintains the gene in a dormant state.

"It's an extremely elegant mechanism. The genes are needed right at the beginning of embryonic development, but rather than deactivate them every time a cell divides, the job is done in one fell swoop, once the genes are no longer required," explains EPFL professor Didier Trono, who co-authored the article. "This process is also involved in the control of viral sequences, which make up almost half of our genome, and must be inactivated very early in development."

This gene-silencing mechanism, which normally takes place in a several-day-old embryo, can also occur accidentally later in life. In many cancer cells, certain genes have been marked by methylation; they have been silenced. If, for example, the gene responsible for controlling cell division has been methylated, the consequences are all too easy to imagine. "The embryonic process, which is designed to silence certain genes, can be fortuitously reactivated, leading to the formation of tumor cells."

It is still not understood why the process stops after the first days of embryogenesis, even though many of the active proteins continue to be expressed in the cell, says Trono. "If we can figure out how this cellular clock works, then we would perhaps be able to understand how the mechanism is reactivated later, leading to the development of cancer."

Journal reference: Cell Reports

Provided by Ecole Polytechnique Federale de Lausanne