Model of ATRA and TNF interaction. ATRA primes NB4 cells for TNF by increasing the production of target genes involved in TNF signaling at early and late time points. ATRA and TNF may combine at early time points to promote the production of genes that have the dual role of inhibiting TNF-mediated apoptosis and promoting differentiation. New target genes are regulated at late time points and at the induction of NF-κB binding by ATRA. The interplay between ATRA-mediated enhanced TNF signaling and synergistic induction of common target genes by TNF and ATRA lead to NB4 differentiation.