Hold the MYCrophone: MYC Invades Enhancers to Control Cancer-Type Gene Programs

Abstract

MYC is an oncogenic transcription factor that binds gene promoters to facilitate oncogenic gene expression. When overexpressed, as is the case in most human cancers, MYC also invades active enhancers—cis-regulatory elements that are critical for regulating gene expression. In previous studies, the regulatory significance of MYC enhancer invasion in cancer cells has been debated. In their study published in Nature Genetics, Jakobsen and colleagues establish a new role for MYC in enhancer regions: regulating cancer type–specific gene programs. Their work reveals a mechanism in which MYC cooperates with other oncogenic transcription factors to recruit epigenetic regulators to enhancers, resulting in an epigenetic “switch” that promotes enhancer activation through BRD4 and RNA polymerase II. This activity was highly cancer-type specific, highlighting gene expression programs that predicted clinical outcome in a subtype-specific manner in patients with breast cancer.