Nature Journal Club

François Fuks

Free University of Brussels

A cancer biologist marvels at how key gene regulators are still revealing hidden talents.

What a difference time makes! It does not seem long since I learned, as a university student and as if it was a closed topic, that the regulation of fruitflies’ ‘homeotic’ genes — which control developmental patterns — is carried out by the Polycomb group of proteins. However, over the past couple of years, thanks to the booming field of epigenetics, these proteins have been given a new lease of life in research labs. They are proving to be multifaceted and dynamic in a range of cellular activities, including cancer progression.

In this light, work by Danny Reinberg at the New York University School of Medicine and his team captured my attention (G. Li et al. Genes Dev. 24, 368–380; 2010). The group addressed one of the burning questions in the field: how exactly does the Polycomb-repressive complex 2 (PRC2), which comprises these Polycomb proteins, recognize and home in on the genes that it regulates? The authors show that the protein encoded by the gene Jarid2, which is also important for development, forms a key component of the PRC2 complex and is involved in its recruitment to target DNA sequences. A slew of recent studies from other groups report similar observations.

The jury is still out on the precise mechanism by which JARID2 aids in the recruitment of PRC2 to its target genes. It is already evident that Jarid2 is only one piece of an elaborate puzzle, and we can expect many exciting discoveries of the remaining pieces. Clearly, Polycomb proteins, which have been well studied since they were discovered more than 50 years ago, are still yielding new insight into gene regulation and other cell activities — and are thus a formidable force to be reckoned with, in both biology and medicine.

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