Super-enhancers (SEs) are large clusters of enhancers that control transcription of genes that define cell identity, and they are frequently acquired by cancer cells to drive key oncogenes. Indeed, the prominent oncogene MYC recurrently acquires SEs in many types of cancer, which may explain its overexpression in a broad array of cancers. Elevated levels of MYC promote transcriptional elongation at promoters of all active genes, thereby amplifying RNA output of the cellular gene expression program. High levels of MYC also lead to increased binding of MYC at enhancers, but the significance of enhancer invasion by MYC is unclear. Here, we propose a model that at tumor cell SEs MYC amplifies the production of enhancer RNAs (eRNAs), which in turn facilitate maintenance of SEs by stabilizing transcription factor and co-factor occupancy. We found that in Burkitt's lymphoma cells SEs depend on high levels of MYC and eRNAs, and that MYC is required for elevated levels of eRNA transcription. We demonstrate that eRNAs directly interact with RNA-binding transcription factors at SEs, and that perturbation of eRNA affects SE signal. Elevated MYC thus contributes to the dynamic formation and maintenance of SEs through amplification of eRNAs. Our results may identify novel RNA targets for new therapies for Burkitt's lymphoma, as well as other cancers. New ways to modulate the immune response may also be revealed by our studies.
Citation Format: Yang Eric Guo, Michael Seyffert, Brian Abraham, Xiong Ji, Richard Young. Oncogenic MYC contributes to tumor super-enhancers via eRNA amplification [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B121.
- ©2016 American Association for Cancer Research.