Harnessing BET inhibitor sensitivity reveals AMIGO2 as a melanoma survival gene.

We utilize the transcriptional effects of BETi in melanoma and identify AMIGO2 as a direct target gene essential for melanoma cell survival both in vitro and in vivo. We further map the enhancer landscape of NHM and melanooma and show that genes regulated by super enhancers are expressed in higher levels, exihibit higher sensitivity to BETi, and over expressed in melanoma relative to NHM. In melanoma, AMIGO2 is regulated by super enhancers, which upon BETi lose their BRD2/BRD4 enrichment, resulting in AMIGO2 silencing. We interogate two NHM culures and four melanoma cell lines for transcriptional changes upon BET inhibition and correlate those wiith changes in enhancer landscape and BRD2/4 occupancy at regulatory regions.