In cancer, an embryonic mechanism gone awry
06.10.12 - Many types of cancer could originate from a mechanism that cells use to silence genes. This process, which is essential in embryonic development, might be accidentally reactivated in tumor cells, according to EPFL scientists.
There are some genes that are only activated in the very first days of an embryo’s existence. Once they have accomplished their task, they are shut down forever, unlike most of our genes, which remain active throughout our lives. EPFL scientists have unveiled part of this strange mechanism. The same process, accidentally initiated later in life, could be responsible for many kinds of cancer. The discovery is described in a recent article in the journal Cell Reports.
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.”
Quenneville et al., The KRAB-ZFP/KAP1 System Contributes to the Early Embryonic Establishment of Site-Speciﬁc
DNA Methylation Patterns Maintained during Development, Cell Reports (2012), http://dx.doi.org/10.1016/j.celrep.2012.08.043