Zurich discovery could help treat cancer

Based on the information in DNA, every cell knows what it must become and what function it must perform. If the genetic information is incorrectly read, cells acquire the wrong identity, which can ultimately lead to cancer.

But the programme that determine which genes are switched on or off as a cell develops does not depend solely on DNA – it is also determined by epigenetic marks, as the University of Zurich (UZH) explains. These act as a molecular switch and coordinate the cell’s specialization within the organism. Until now, researchers were not able to explain how this DNA methylation is regulated and how it can become defective.

UZH researchers have now made an important step in this regard by showing that the protein DNA methyltransferase 3A (DNMT3A) is responsible for positioning the methylation to the right place on the DNA. 

“DNMT3A places itself preferably in close vicinity to genes that play an important role for development and makes sure that the DNA methylation around these genes is maintained,” said Massimiliano Manzo, lead author of the study. 

“The DNA methylation around these genes works like a container that ensures that H3K27me3, another epigenetic modification, which normally regulates these genes, is positioned correctly.” This means that two epigenetic layers regulate these essential genes.

The study’s findings provide important basic insights for cancer research, according to UZH. DNMTA3 is one of the most frequently mutated genes in an aggressive type of leukaemia and plays a significant role in how the disease develops.

“Our findings point toward a previously unknown function of the DNMT3A protein in the interaction of these two epigenetic modifications that are normally not directly linked. We hope that these new insights will allow us to increase our understanding of the molecular mechanisms that result in cancer and to more effectively treat this aggressive type of leukaemia,” said UZH professor Tuncay Baubec.