Experimental cancer treatments that harness souped-up segments of DNA called super-enhancers to activate genes are working their way to the clinic for the first time. But scientists are still debating how these elements work – and whether they represent a fundamentally new way of regulating genes.
Form vs. function
Super-enhancers seem to be particularly important in embryonic stem cells, and they are sometimes hijacked by cancer cells to drive the aberrant gene activity that fuels tumour growth.
And super-enhancers also attract unusually large numbers of the proteins required to activate the genes they control. These clusters of enhancers and proteins might allow cells to tightly regulate important genes, ensuring that they will be turned on exactly when needed and in precisely the right amount, says Christopher Vakoc, who studies gene expression at Cold Spring Harbor Laboratory in New York and has advised Syros.
“It’s all about precision,” says Vakoc. “When the cell goes to that much effort to control a gene, it’s because the product of that gene is pivotal in biology.”
Although mammalian cells have thousands of enhancers, they typically have only a few hundred super-enhancers. As a result, researchers now use super-enhancers as a signpost for important genes, says Hennighausen. Understanding how they work could shed light on how cells adopt their identities. But researchers don’t know whether the enhancers in a cluster act independently, or whether they work synergistically in a new form of gene regulation.