In this study, we use three criteria to demonstrate the relationship between Fgf16 and Tbx22 epigenetics in palatogenesis following ATRA-induced cleft palate formation: 1) identification of differential DNA methylation levels from site to gene of susceptible genes, 2) identification of changes in gene expression, and 3) identification of changes in gene expression related to cleft palate vs. DNA methylation level. The gene discussed is TBX22; the disease is cleft palate.