eCLIP-Seq of endogenous/exogenous MYC in MCF-7 cells.

MYC binds to thousands of promoters and exerts an amplification effect on expression of most genes. Meanwhile, MYC drives tumourigenesis through the regulation of a unique set of cancer-specific targets that differ from its targets in normal cells. The discrepancy in MYC-mediated gene regulation in tumours versus normal cells has not been fully elucidated. In this study, we discovered that MYC protein has a broad RNA binding spectrum including promoter-associated RNAs (paRNAs) and enhancer RNAs (eRNAs). MYC RNA binding peaks colocalize with its DNA binding sites, but they are not dependent on its HLHLZ domain or transactivation domain. By integrating multiple dimensional data sets from cancer cells and tumour samples, we show that the MYC-bound paRNAs and eRNAs can shape MYC chromatin interaction to regulate gene transcription. Finally, we identified and characterized a novel MYC-bound eRNA, which we refer to as MERG1, that plays essential roles in the ERα+ breast cancer tumourigenesis. Mechanistically, MERG1 interacts with MYC and enhances MYC binding to the enhancer and promoter of the GREB1 gene. This process specifically amplifies expression of the MYC target gene GREB1 and accelerates tumour progression. Our study demonstrates that MYC interaction with paRNAs and eRNAs contribute to its specific amplification of gene expression in tumourigenesis. eCLIP-Seq of endogenous, exogenous full-length, and exogenous truncated MYC in MCF-7 cells.