MYCN and neuroblastoma: Furthermore, the promoters of TrkA are repressed not only by DNA methylation but also directly by EZH2-mediated histone modification in another promoter region [95] Since both MYCN and MYC directly induce EZH2 expression through binding at its promoter region [96,97], EZH2-mediated inactivation of the tumor suppressors in 1p36 may conceivably be a major route toward development of unfavorable neuroblastomas with MYCN amplification (Figure 4B).