As discussed above, although negative regulation of de novo methylation by UHRF1/2 likely serves as a mechanism enhancing the fidelity of DNA methylation inheritance in somatic cells, excessive downregulation of DNMT3A by overexpressed UHRF1/2 would drive the gradual loss of DNA methylation and lead to DNA hypomethylation in cancer (Figure 7h). The gene discussed is DNMT3A; the disease is cancer.