Microsatellite enhancers can be targeted to impair tumorigenesis.

ABSTRACT

Dysregulation of repetitive elements has been implicated in many cancers and other human diseases; however, the role of repetitive elements remains largely unexplored. In this issue of Genes & Development, Boulay and colleagues (pp. 1008-1019) explore the ability of GGAA repeats to act as alternative enhancers activated by EWS-FLI1 in Ewing sarcoma and contribute to tumorigenesis. Using CRISPR-mediated epigenome editing, repression of EWS-FLI1 targeted microsatellite enhancers halted aberrant gene expression and impaired the growth of Ewing sarcoma xenografts in vivo. The study reveals the regulatory capacity of repetitive elements in cancer and offers insight into therapeutic targets for Ewing sarcoma.