Study Identifies Roles of PRC1 and PRC2 in Maintaining Cellular Identity

Trinity College Dublin researchers have discovered new mechanisms involved in establishing cellular identity, including that PRC2.1, PRC2.2, and cPRC1 are universally co-displaced from, and co-recruited to, Polycomb target genes during cell-fate transition. This new discovery has potential translational impacts in cancer biology and associated targeted treatments.

The team focused on the workings of Polycomb protein complexes, PRC1 and PRC2, as they are “strict librarians” inside cells, according to Ellen Tuck, co-author of the paper published in Molecular Cell. “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.” 

Scientist have long wondered why there are two forms of PRC2 in cells (PRC2.1 and PRC2.2), especially after the team previously showed that the two forms of PRC2 target the same regions of DNA and do the same job. So why do we need two versions? 

The new discovery answers that question, as the team found that PRC2.1 and PRC2.2 recruit different forms of the PRC1 complex to DNA, which is 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,” explains first author Eleanor Glancy.

This finding could further impact in 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," adds senior author Adrian Bracken. “A firm and comprehensive understanding of the workings of these complexes is critical to figuring out new ways to target them in cancer settings.”