Scientists led by a team at Trinity College Dublin (TCD) have made a breakthrough in relation to cellular identity, which has the potential to impact cancer treatments.

Cellular identity is a process that ensures the billions of cells in our bodies do the correct job. The scientists have discovered new mechanisms involved in establishing this process. The result was so surprising that the team initially thought it was an error.

Their research focuses on the workings of Polycomb protein complexes, PRC1 and PRC2. According to Ellen Tuck, a PhD student at TCD, these proteins act as “strict librarians” inside cells.

“PRC1 and PRC2 block access to certain areas of the genetic library, such that a neuron cell won’t have access to muscle genes, and it doesn’t get confused in its cellular identity,” she explained.

Ms Tuck is part of a team headed up by Prof Adrian Bracken. A puzzle regarding PRC2 has intrigued this team and other scientists in the field for years. Two forms (PRC2.1 and PRC2.2) exist in the cell but the Bracken lab previously showed that the two forms of PRC2 target the same regions of DNA and do the same job. So why are two versions needed? 

This latest discovery from the lab takes an exciting step towards answering this conundrum. The scientists found that PRC2.1 and PRC2.2 recruit different forms of the PRC1 complex to DNA, which finally explains why two versions are needed.

“This took us by complete surprise. We initially thought there must have been a technical issue with the experiment, but multiple replications confirmed that we had in fact stumbled upon a fascinating new process that reshapes our understanding of the hierarchical workflow of Polycomb complexes. We were dancing around the lab,” said Dr Eleanor Glancy, a PhD graduate of the Bracken laboratory.

This research by TCD scientists could have a major impact on cancer biology research as the genes encoding Polycomb proteins are frequently mutated in cancers.

“My team currently studies the effects of these mutations in childhood brain cancers and adult lymphomas, seeking to understand what biological mechanisms go awry and how we can target these complexes with more effective treatments.

“A firm and comprehensive understanding of the workings of these complexes is critical to figuring out new ways to target them in cancer settings. Therefore, this work will be built upon here and by other researchers worldwide to advance our approach to many cancers,” Prof Bracken explained.

The work was spearheaded by Dr Glancy, together with postdoctoral researcher, Dr Cheng Wang. It also involved important collaborative support from scientists in Italy and the Netherlands.

The findings are published in the journal, Molecular Cell, and more information about the research work of the Bracken laboratory can be found here.