Thus, in 2 distinct pediatric cancers, NB and RMS, our results demonstrate that MYCN directly activates canonical MYC target genes mainly through binding to the promoters of these genes, while repressing tissue-specific differentiation genes mainly through binding to both enhancers and promoters of these genes (Figs 1I–1M and 2E–2I). This evidence concerns the gene MYC and neuroblastoma.