Figure 9.

A model for tumorigenesis. (Arrow) Residual EGL occurs in the setting of Ptch1 heterozygosity. Unmethylated Hic1 (green promoter 1b) allows for Hic1 expression. Hic1 binds the Atoh1 enhancer leading to transcriptional repression and differentiation, which depletes the presumed precursor lesion. If Hic1 is hypermethylated (red promoter 1b), expression is silenced leading to uncontrolled Atoh1 expression and tumorigenesis is promoted as demonstrated by a representative image of a Ptch1^+/− Hic1^+/− tumor. (IGL) Internal granule cell layer; (ML) molecular layer; (Tu) medulloblastoma.