Scientists Identify New Regulatory Protein Complex With Unexpected Behaviour

Throughout embryonic development, proteins known as Polycomb group complexes turn genes off when and where their activity should not be present, preventing specialised tissues and organs from forming within the wrong places. They also play a huge role in processes like stem cell differentiation and cancer.

In a study published online in Nature, scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, identified a new Polycomb group complex, and were surprised by how it acts.

Another Polycomb group complex was already recognized to silence genes by placing a chemical tag near them. Juerg Mueller and his group at EMBL found that the new Polycomb complex they discovered, PR-DUB, removes that same tag.

These microscopy images show the region of the embryo larva that will develop into the adult fruit fly’s wing. In cells genetically manipulated so that PR-DUB cannot remove the gene-silencing tag (left), a gene which would normally be silenced becomes turned on (red) - a situation which is corrected when PR-DUB’s activity is restored (right).

“Surprisingly, this new complex which takes the tag off seems to act in the same tissues and at the same developmental stages as the one which puts the tag on,” says Mueller, “and both opposing activities must occur to keep the gene silenced in our model organism, the fruit fly Drosophila.”

The reason behind this unexpected behaviour is not experimentally confirmed, but it might be a case of fine-tuning, with the newly-found complex ensuring that the chemical tagging is kept at its optimal level.

The human equivalent of PR-DUB is proven to be a tumour-suppressor, and Mueller and colleagues discovered that, in test-tubes at least, it behaves exactly the same way as the fruit fly complex, removing that same gene-silencing tag. Knowing how the complex acts within the fruit fly could assist scientists uncover its function within the cells of mammals for example ourselves, and thus begin to simplify its relation to cancer.

Source: European Molecular Biology Laboratory.