Jarid2 may break the Polycomb silence

Historically, fly and human Polycomb proteins were considered textbook exemplars of transcriptional repressors, or proteins that silence the process by which DNA gives rise to new proteins. In a direct challenge to that dogma, Stowers Investigator Ali Shilatifard, PhD, and his team report that in the fruit fly Drosophila melanogaster a component of the Polycomb repressive complex 2 (PRC2) occasionally activates gene expression.

Polycomb proteins, a group of chromatin-binding factors, were initially found to control how developing fly embryos undergo segmentation. Subsequently, researchers discovered that humans also express a gaggle of proteins resembling fly Polycomb factors and that these proteins have crucially significant roles: under normal conditions PRC2 proteins are required for the differentiation of stem cells, but when overactive, they act as oncogenes in lymphoma and breast and prostate cancer.

“Our approach is to use Drosophila as a model to learn how Polycomb group proteins function in the context of cancer,” says Shilatifard, who studies mechanisms underlying leukemia in yeast, fruit flies and mammalian cells. “In this study, we found that a new component of the PRC2 complex, Jarid2, maintains repression of some genes, but also potentially activates other target genes.”

Recent reports implicate Jarid2 in diseases as diverse as multiple sclerosis and schizophrenia. But most significantly for the Shilatifard lab are studies linking both PRC2 and Jarid2 to myeloid cancers such as leukemia. “The theme of our lab is factors that regulate the yin and yang of transcription,” says Shilatifard, citing his interest in both of the Polycomb proteins and their polar opposites, the Trithorax activator proteins, which have also been linked to leukemia. “Our overall goal is to gain insight into both.”

The study was published in the May 2012 issue of the journal Molecular and Cellular Biology.