HCF-1 interacts with MYC box IV of MYC. HCF-1 is a conserved chromatin associated protein that often works with WDR5 as part of epigenetic writer complexes. It interacts with MYC through MbIV, which carries a sub-prime “HCF-1 binding motif” (HBM). Interaction of MYC with HCF-1 is important for regulating the expression of genes involved in ribosome biogenesis (RiBi) and mitochondrial vigor. This interaction is important for tumor onset and maintenance. We seek to understand how and why MYC uses HCF-1 for its tumorigenic functions and whether this interaction can be targeted to treat cancer.